Formate test for bedside diagnosis of methanol poisoning.

Methanol poisoning kills thousands of people every year and remains a diagnostic challenge, especially where the resources are scarce, but also in high-income countries worldwide. We are in the course of developing a bedside strip to detect formate - the toxic metabolite of methanol. We hereby present the first clinical methanol case where formate was detected bedside from a drop of blood: The patient, a 61-year-old male, was admitted with a suspect methanol poisoning and severe metabolic acidosis. The test strip was positive after 3 minutes. Sodium bicarbonate (500 mmol/L), fomepizole, dialysis and folinic acid were given based on the positive test. The diagnosis was some hours later confirmed by GC-MS, showing a methanol concentration of 62 mmol/L (200 mg/dL) and a formate concentration of 19 mmol/L. Implementation of this technology into routine clinical use can potentially offer an opportunity for a step change in the management of methanol poisoning.

Beta-hydroxybutyrate and pyroglutamate can be included in a rapid GC-MS screening method for differential diagnosis of metabolic acidosis.

A rapid gas chromatographic mass spectrometric method for measuring anions associated with acute anion gap metabolic acidosis is described. The method is an extension of a previous method. The method quantifies glycolic acid, beta-hydroxybutyric acid with good linearity and pyroglutamic acid with a reproducible curvature relation between 1 and 20 mmol/L and can help the clinician distinguish effectively between ethylene glycol poisoning, alcoholic and diabetic ketoacidosis and cysteine deficiency so early that it will have clinical consequences.

A novel bedside diagnostic test for methanol poisoning using dry chemistry for formate.

BACKGROUND: The standard diagnostic approach to methanol poisoning is chromatographic measurement of methanol on centrally placed stationary equipment. Methanol poisoning in places where such equipment is unavailable is thus often not diagnosed. Methanol is metabolized to a toxic metabolite, formate; the presence of this compound indicates methanol poisoning. We have developed an enzymatic test for formate and modified it into a portable dry chemistry system that could be used anywhere. METHODS: The method consists of two enzymatic steps: Formation of NADH from NAD by formate dehydrogenase, and subsequent use of NADH as a reductant of a tetrazolium into a formazan dye that can be quantified photometrically or visually. RESULTS: The photometer gave a good correlation of R(2) = 0.9893 in serum and R(2) = 0.9949 in whole blood, showing an instrumental detection limit of less than 1 mM (4.5 mg/dL). The visual readings showed a correlation of R(2) = 0.8966. Users experienced some difficulty in separating the negative control from the low positives. CONCLUSIONS: We have documented the feasibility of an affordable formate strip test for bedside diagnosis of methanol poisoning and for screening of metabolic acidosis of unknown origin. Visual reading is possible, but a reader will improve reliability at lower levels of formate. Future studies are necessary to study the sensitivity and specificity towards other causes of metabolic acidosis and other acids present in human blood.

Dietary intake of menaquinone-4 may determine hepatic and pancreatic menaquinone-4 in chickens.

OBJECTIVE: The aim of this study was to determine the biological effects of natural dietary intake of vitamin K as phylloquinone (K(1)) and menaquinone-4 (MK-4) and a control diet also containing menadione (K(3)) on levels of K(1) and total MK-4 (menaquinone-4) and menaquinone-4-2,3-epoxide (MK-4O)) in liver and pancreas, and on femur bending resistance in a fast-growing animal model. DESIGN: Chickens were fed four wheat-based diets from day 11 to day 22 after hatching. The diets contained different combinations of fat sources: rapeseed oil, animal rendered fat, soybean oil and hydrogenated soybean oil. Concentration of K(1) in the three experimental diets was 120 ng/g whereas MK-4 levels were 23, 52 and 63 ng/g respectively. The control diet contained 157 ng K(1)/g, 75 ng MK-4/g and 2.250 ng K(3)/g. RESULTS: Growth rates and femur strength confirmed adequate supply of nutrients and vitamin K in the test groups. There were no significant differences in femur bending resistance among the test groups, but these were higher than the control. K(1), MK-4 and MK-4O were found in liver. In pancreas, mainly MK-4O was found with small amounts of MK-4, but none had content of K(1). In the test groups the hepatic levels of MK-4 and MK-4O reflected the dietary intake of MK-4. CONCLUSION: The chickens were in good health with good bone resistance without supplements of K(3) in the feed, but at least a natural content of 23 ng MK-4/g feed. Liver and pancreas appears to use MK-4 in different ways.

Dietary vitamin K2 supplement improves bone status after lung and heart transplantation.

BACKGROUND: Osteoporosis is a problem after transplantation. Studies since the last year indicate that vitamin K plays a role in optimal bone health. The aim of this randomized, double blind, prospective longitudinal study was to investigate the effect of a dietary supplement with vitamin K2 (180 microg menakinon-7) on bone mass, the first year after lung and heart transplantation. METHODS: After preoperative baseline investigation of bone mass and bone-related biochemistry, 35 lung and 59 heart recipients were postoperatively randomized to vitamin K2 or placebo and reinvestigated the following year. RESULTS: In all recipients, 1 year after solid organ transplantation, the difference between vitamin K2 and placebo for the lumbar spine (L2-L4) bone mineral density (BMD) was 0.028 (SE 0.014) g/cm(2), P=0.055 and for L2 to L4 bone mineral content was 1.33 (SE 1.91) g/cm(2) (P=0.5). In lung recipients separately, the difference for bone mineral content was 3.39 g (SE 1.65), P=0.048 and in heart recipients 0.45 (SE 0.02) g, P=0.9 after controlling for baseline measures. In a forward stepwise linear regression analysis fitted to model differences in the L2 to L4 BMD, controlled for possible confounding variables (including use of bisphosphonate), and the only significant predictors were organ (B=-0.065 g/cm(2), P<0.001) and vitamin K2 (B=0.034 g/cm(2), P=0.019). Insufficient vitamin D status was common, and the parathyroid hormone was highest in the K2 group indicating a higher need for vitamin D. CONCLUSIONS: One year of vitamin K2 supplement suggest a favorable effect on lumbar spine BMD with different response in lung and heart recipients. Vitamin D status should receive more attention.