Biochemical diagnosis and monitoring of diabetes: a laboratory perspective for the nineties.
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Biomedical subjects
Publications and source records attributed to G Letellier.
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We evaluated a serum fructosamine (glycated serum proteins) assay for efficacy in the diagnosis and follow-up of diabetic patients. A Roche reagent kit, based on nitroblue tetrazolium reduction in alkaline medium, was used in COBAS FARA centrifugal analyzer. We demonstrated that this method is precise, linear and unaffected by serum hemolysis. However, bilirubin affected the test positively and lipemia negatively. Fructosamine (F) correlated positively with total protein (P) (r = 0.809) and albumin (r = 0.746) in a group of 48 non-diabetic individuals. A good correlation was observed between F and glycated hemoglobin from the sera of 514 patients (r = 0.794). A better correlation (r = 0.838) was obtained when F was corrected for P concentration (F/P). Different F and F/P means were calculated only in patients with overt diabetes, compared to normals. Gestational diabetes was associated with a highly significant F increase. However, its low sensitivity (21%) precludes the use of F as an effective screening test for that condition. Nevertheless, because of its simplicity, low cost and rapidity in reflecting changes in the metabolic control of diabetes, F should be considered a valuable test to assess glycemic control in diabetic patients.
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We shall describe a simple technique to prepare concentrated sera that will have a near normal osmolality. A pool of sera is first frozen for 72 h at -20 degrees C and then allowed to thaw at 6 degrees C for 16 h. Care is taken to avoid any shaking of the bottle. The surface serum is then cautiously aspirated with a pipette. The left-over serum is mixed and filtered. To decrease the osmolality of this concentrated serum, we treated it with 200 mg of resin (Rexyn AG 501, H-OH) per 5 mL serum and then filtered it to eliminate the resin. We studied the effects of the height of the liquid column, the freezing temperature, the volume of serum decanted, the resin concentration and the duration of the extraction step. We also evaluated the stability of this concentrated serum at 6 degrees C, -20 degrees C and -70 degrees C. We also verified whether readjustment of the pH of the concentrated resin-treated serum would have improved its stability at -20 degrees C.
We have investigated the effect of 20 drugs on the accuracy of results obtained from seven instruments now widely used in clinical biochemistry laboratories: Abbott VP, aca II, Cobas Bio, Ektachem 400, Hitachi 705, KDA and SMAC. Eleven to 18 constituents were analysed on each instrument. Our results lead us to the following conclusions: (1) only rarely does drug interference with a method lead to a clinically significant change in a measured value; (2) the magnitude of the change may relate linearly or non-linearly to the drug concentration but is usually independent of the target analyte concentration; (3) interference with a chemical reaction on one instrument does not always mean that the same reaction will be altered in the same way on other instruments; (4) no interferences were found for drugs with therapeutic levels in the low micro-molar range; (5) in most cases the interference could not be predicted from the chemical nature of drug.
It is well known that some cephalosporins interfere with the Jaffé reaction for creatinine measurement. This interference varies according to the thirteen instruments and eighteen methodologies studied. Our study has shown that: the proportion of picric acid, NaOH and serum have only a slight effect on the interference; the addition of a buffer to the NaOH solution increases the interference due to cephalothin and cephaloridine, but lessens that due to cefoxitin; dialysis decreases the interference; in kinetic methods, the choice of times at which readings are made influences the magnitude of the interference; a higher incubation temperature increases the effect of cefoxitin and decreases the effects of cephalothin and cephaloridine; pre-incubation with NaOH decreases the interference due to cefoxitin, but has no significant effect on the interference due to cephalothin or to cephaloridine.
Acute necrosis of R3230AC mammary tumor or thyroid carcinoma subcutaneously implanted in F344 rats was achieved by injection of a strongly hypertonic hexose and serotonin solution at 37 degrees C into and around the tumors. Changes in gross metabolism, hematology, and blood chemistry were then followed over a 9-day period, and they were most marked during or at the end of the first 24 hours. Food intake of the rats was sharply reduced, whereas drinking and diuresis were increased. Marked hemodilution and increased serum concentrations of aspartate aminotransferase, potassium, and uric acid were observed, as well as stable serum concentrations of sodium and chloride. Glucose overload, as opposed to fructose overload, led to secondary hypoglycemia. From day 2 food consumption returned to normal and increased thereafter. Water intake and urine output remained high. After an initial loss, body weight caught up with that of control rats. Hematocrit recovered partially, whereas blood chemistry progressively returned to about normal values.
The seasonal variations of eighteen parameters of a biochemical profile were studied under standardized conditions. More than 2,600 blood samples from a homogeneous group of women aged 30 to 39 years were processed on a well controlled instrument over a four-year period. Monthly means were first calculated and then seasonal means for two delimitations of seasons and for different combinations of years. Even though many statistically significant differences were found between seasons, only in the case of two parameters, uric acid and triglycerides, was the percentage of difference between the highest and the lowest seasonal means greater than the inter-assay CV of the methods. For these two parameters the results of other age groups of women and men were also computed. Uric acid was higher in summer compared to fall by 5% in the case of women aged 30-39 and by 7% in the case of men aged 30-39, the method inter-assay CV being 4.5%. Triglycerides were 6% higher during spring compared to fall for women aged 30-39, but surprisingly, 22% higher in winter compared to fall in the case of men aged 30-39. For younger groups of men the difference is much smaller and for men aged 20 to 25 years the difference is not significant. In general, we have been unable to confirm the variations previously reported by many authors.
Reference values for two well defined populations, four day old newborns and post-partum women, are given for 19 parameters measured on a SMAC system. These values are respectively compared to those established previously for children from one to three year old and those of women aged 20-39. The values for the new borns are higher for eight parameters and lower for nine others. The values for post-partum women are higher for seven parameters and lower for six others. These two groups have therefore distinct reference values for most of the parameters studied.
1. We have studied the in vitro effect of 39 drugs on 17 biochemical parameters determined by a SMAC System. Only two drugs were found to interfere: ascorbic and theophyline. 2. The ascorbic acid lowers the glucose and the bilirubine values; it increases the creatinine and the uric acid concentration. At concentration smaller than 5 mg/dl of this drug, these effects are negligible. 3. We have found a new drug interference: theophylline inhibits the alkaline phosphatase and LDH activities. This effect is not negligible on alkaline phosphatase for therapeutic levels of this drug; the action on LDH can be ignored at normal therapeutic range. 4. For a given drug, we have found different interference with biochemical parameters determined with various commercial lyophlised control sera or a liquid pool of sera. This indicates that the type of sera used in drug interference studies must be described.
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Explore the source record for details and available documents.
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