Assay for Urinary Methylmalonic Acid by High-pressure Liquid Chromatography

An assay for urinary methylmalonic acid by high-pressure liquid chromatography was devised. Methylmalonic acid could be assayed over a range of 5–80 μg by this method, which is one of the most convenient and useful assays for the acid in urine as an index of cobalamin deficiency.     

Autoimmune Haemolytic Anaemia and Mefenamic Acid Therapy

Three patients developed autoimmune haemolytic anaemia while being treated with mefenamic acid. In each case the autoimmune haemolytic anaemia was of the warm antibody γG type, and the antibodies had some rhesus specificity. All three patients recovered when the drug was withdrawn.Attempts to inhibit or enhance the activity of the antibody in vitro were unsuccessful.Direct antihuman globulin tests were made in.the red cells of 36 patients receiving long-term mefenamic acid therapy, but only one was found to be transitorily positive.     

Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer

Background/Aims

Normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, and can therefore be misleading. High levels of Methymalonic Acid (MMA) and Homocysteine (HC) have been identified as better indicators of B-12 deficiency than the actual serum B-12 level itself. We evaluated the prevalence of vitamin B-12 deficiency using appropriate cut-off levels of vitamin B-12, MMA and HC, and determined the relationship between serum levels of vitamin B-12, MMA and HC in cancer.

Methods

This is a cross-sectional study using a consecutive case series of 316 cancer patients first seen at Cancer Treatment Centers of America^® (CTCA) at Midwestern Regional Medical Center between April 2014 and June 2014. All patients were evaluated at baseline for vitamin B-12 (pg/mL), MMA (nmol/L) and HC (μmol/L) levels. In accordance with previously published research, the following cut-offs were used to define vitamin B-12 deficiency: <300 pg/mL for vitamin B-12, >260 nmol/L for MMA and >12 μmol/L for HC. The relationship between B-12, MMA and HC was evaluated using Spearman''s rho correlation coefficient and cross-tabulation analysis. Receiver Operating Characteristic (ROC) curves were estimated using the non-parametric method to further evaluate the diagnostic accuracy of vitamin B-12 using Fedosov quotient as the "gold standard".

Results

Mean age at presentation was 52.5 years. 134 (42.4%) patients were males while 182 (57.6%) were females. Median vitamin B-12, MMA and HC levels were 582.5 pg/mL, 146.5 nmol/L and 8.4 μmol/L respectively. Of 316 patients, 28 (8.9%) were vitamin B-12 deficient based on vitamin B-12 (<300pg/mL), 34 (10.8%) were deficient based on MMA (>260 nmol/L) while 55 (17.4%) were deficient based on HC (>12 μmol/L). Correlation analysis revealed a significant weak negative correlation between vitamin B-12 and MMA (rho = -0.22) as well as B-12 and HC (rho = -0.35). ROC curves suggested MMA to have the best discriminatory power in predicting B-12 deficiency.

Conclusion

Vitamin B-12 is poorly correlated with MMA and HC in cancer. Using serum vitamin B-12 alone to evaluate B-12 status in cancer may fail to identify those with functional deficiency. A thorough clinical assessment is important to identify patients that may have risk factors and/or symptoms suggestive of deficiency. These patients should have additional testing of MMA and HC regardless of their B-12 levels.     

Analysis of Excretion Fraction of Uric Acid

Excretion fraction of uric acid (EF_UA), is one of the most important hallmarks for diagnosis of familial juvenile hyperuricemic nephropathy (FJHN) and hereditary renal hypouricemia. EF_UA was measured in 20 patients with FJHN. However, low excretion fraction (<6%) was found also in healthy FJHN family members and healthy controls (ref. ranges EF_UA: men 6–12%, women 6–20%). Similar finding of low EF_UA was reported recently. Distribution of EF_UA was further studied in 2,416 healthy controls, which were selected from 6,000 samples and divided according to age. In conclusion, finding of low EF_UA in family members is a risk factor for renal damage and indication for purine metabolic investigations with subsequent molecular biology analysis. As EF_UA could be found also in healthy controls—it should be interpreted with care and other features of FJHN (such as hyperuricemia, progressive renal disease in family) should be taken to account.     

Porphobilinogen and Delta-Aminolevulinic Acid Excretion in Multiple Sclerosis

The excretion of delta-aminolevulinic acid and porphobilinogen in the urine of 31 patients with multiple sclerosis did not differ significantly from that of 51 hospitalized control patients or eight patients with poliomyelitis. There was no relationship between exacerbations, remissions or duration of the illness, and levels of delta-aminolevulinic acid or of porphobilinogen. These assays therefore appear to be of no value in the differential diagnosis of multiple sclerosis or in following the severity or stage of this illness. Whereas demyelination does occur in acute porphyria where the levels of delta-aminolevulinic acid and porphobilinogen are elevated, the converse is not true; that is, demyelination is not always associated with an increase in the excretion of porphobilinogen or delta-aminolevulinic acid.     

Ribonucleic Acid Synthesis and Glutamate Excretion in Escherichia coli

Cultures of Escherichia coli excreted glutamate into the medium when protein synthesis was blocked in RC(rel) strains or when it was blocked with chloramphenicol in either RC(str) or RC(rel) strains. Both of these conditions resulted in continued ribonucleic acid (RNA) synthesis in the absence of protein synthesis. Glutamate was also excreted by both RC(str) and RC(rel) strains when RNA synthesis was inhibited by uracil starvation or by treatment with actinomycin D. It is proposed that, in each of these cases, glutamate excretion resulted from an increase in the permeability of the cell membrane.     

Uric Acid Excretion in Isoparorchis hypselobagri (Billet, 1898)

The nature and amount of excretory products of Isoparorchis hypselobagri, a digenetic trematode inhabiting the swim bladder of Wallago attu have been studied. The parasites were kept in PBS media without glucose (control) and with glucose (treated) successfully up to 300 h and different excretory products were estimated at an interval of 12 h. The quantitative estimation of excreted uric acid in I. hypselobagri was revealed less in amount in the flukes which were kept in vitro in the control incubation media than those considered from the treated incubation media. The highest amount of uric acid excreted in control media was 6.72 mg % at 204 h, and in treated condition 16.658 mg % after 216 h of incubation. The lowest amount of uric acid excreted, 0.186 mg % in control media after 252 h of incubation and 2.896 mg % in treated media after 192 h of incubation. The rate of excretion of uric acid in treated condition after every 12 h of incubation is much higher than the control. Significant amount of uric acid have also been recorded in the swim bladder washings of host. It is apparent that the amount of excreted uric acid depends on the number and weight of the parasites harbor. Results suggest that I. hypselobagri is ammonotelic, ureotelic and also uricotelic trematode.