Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men.

Deficient levels of folic acid and vitamin B12 are associated with elevated chromosome damage rate and high concentrations of homocysteine in the blood. We have therefore performed a study to determine the prevalence of folate deficiency, vitamin B12 deficiency and hyperhomocysteinemia in 64 healthy men aged between 50 and 70 years, and evaluate the relationship of these micronutrient levels in the blood with the micronucleus frequency in peripheral blood lymphocytes. We also performed a placebo-controlled, double-blind intervention study to determine whether supplementation of the diet with a daily dose of 0.7 mg (as a supplement in cereal) or 2.0 mg (in a tablet) over a period of 4 months resulted in a significant alteration of folate status, homocysteine status and the micronucleus index. Twenty-three per cent of the men were serum folate deficient (<6.8 nmol/l), 16% were red blood cell folate deficient (<317 nmol/l), 4.7% were vitamin B12 deficient (<150 pmol/l) and 37% has plasma homocysteine levels >10 micromol/l. In total, 56% of the men had one or more abnormal blood values for folate, vitamin B12 or homocysteine. The micronucleus index of these men (n = 34) in cytokinesis-blocked binucleated cells (19.2 +/- 1.1) was significantly elevated (P = 0.02) when compared to the micronucleus index of the rest of the men who had normal levels of folate, vitamin B12 and homocysteine (16.3 +/- 1.3, n = 30). Interestingly, the micronucleus index in men with normal folate and vitamin B12, but homocysteine levels >10 micromol/l (19.4 +/- 1.7, n = 15) was also significantly higher (P = 0.05) when compared to those with normal folate, vitamin B12 and homocysteine. This novel result was also supported by the observation that the micronucleus index and plasma homocysteine were significantly (P = 0.0086) and positively correlated (r2 = 0.172) in those subjects who were not deficient in folate or vitamin B12. The micronucleus index was not significantly correlated with folate indices, but there was a significant (P = 0.013) negative correlation with serum vitamin B12 (r2 = 0.099). Daily supplementation of the diet with 0.7 mg free folic acid in cereal for 2 months followed by 2.0 mg free folic acid via a tablet produced a 4-fold increase in plasma folate, a 2.6-fold increase in red blood cell folate and a 11% reduction in plasma homocysteine; however, these changes were not accompanied by a reduction in the micronucleus index. In conclusion, it is apparent that elevated homocysteine status, in the absence of vitamin deficiency and low, but not deficient, vitamin B12 status are important risk factors for increased chromosome damage in lymphocytes.

In vitro modeling of spinal anesthesia. A digital video image processing technique and its application to catheter characterization.

BACKGROUND: Maldistribution of intrathecal local anesthetic has recently been implicated as a contributor to neurotoxic injury. In vitro modeling can be used to understand the distribution of anesthetic agents within the subarachnoid space. We describe an in vitro modeling technique that uses digital video image processing and its application to catheter injection of local anesthetic. METHODS: A clear plastic model of the subarachnoid space, including a simulated spinal cord and cauda equina, was filled with lactated Ringer's solution. Phthalocyanine blue dye of known concentration was injected into the model through small-bore (28-G) and large-bore (18-G) catheters. Injections were performed at a variety of controlled rates and sacral catheter positions, and the propagation of dye throughout the model was recorded on videotape, digitized by computer, and converted to a two-dimensional image of dye concentration. A subset of data was compared with results obtained from spectrophotometric analysis. RESULTS: There was a strong correlation (r = 0.98) between data obtained with analysis by digital video image processing and those obtained spectrophotometrically. Catheter size, catheter angle, and injection rate significantly influenced the distribution and peak concentration of simulated anesthetic. No major differences in distribution or peak concentration were observed with the two types of 28-G catheters. CONCLUSIONS: The digital video image processing technique can be used to quantify anesthetic distribution rapidly within a model of the subarachnoid space without disturbing the distribution. The current results demonstrate a strong dependence of anesthetic distribution on catheter angle, catheter size, and injection rate. Comparisons between 28-G catheters suggest that the difference in reported incidence of cauda equina syndrome associated with different 28-G catheters cannot be explained on the basis of differences in anesthetic distribution.