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V Herbert

Publications and source records attributed to V Herbert.

At least 19 recordsLinked to original sources
PubMed1992

Iron disorders can mimic anything, so always test for them.

Routinely measuring iron status is necessary because not only are about 6% of Americans in significant negative iron balance, but about 1% have iron overload. Serum ferritin is in equilibrium with body iron stores, and is the only blood test that measures them. Barring inflammation, each one ng (0.0179 pmol) ferritin/ml of serum indicates approximately 10 mg (0.179 mmol) of body iron stores. Very early Stage I positive balance is best recognized by measuring saturation of iron binding capacity. Conversely, serum ferritin best recognizes early (Stage I and II) negative balance. Deviations from normal are: 1. Both stages of iron depletion (i.e. low stores, no dysfunction). Negative iron balance Stage I is reduced iron absorption producing moderately depleted iron stores. Stage II is severely depleted stores, without dysfunction. These stages include over half of all cases of negative iron balance. Treated with iron, they never progress to dysfunction, i.e. to disease. 2. Both stages of iron deficiency. Deficiency is inadequate iron for normal function, i.e. dysfunction, disease. Negative balance Stage III is dysfunction without anemia; Stage IV is with anemia. 3. Positive iron balance: Stage I is a multi-year period without dysfunction. Supplements of iron and/or vitamin C promote progression to dysfunction (disease). Iron removal prevents progression. Stage II is iron overload disease, encompassing years of insidiously progressive damage to tissues and organs from iron overload. Iron removal arrests progression.

Adolescent↗
PubMed1992

Everyone should be tested for iron disorders.

Routinely measuring iron status is necessary because about 6% of Americans have negative iron balance, about 10% have a gene for positive balance, and about 1% have iron overload. Deviations from normal iron status are as follows. (a) Stage I and II negative iron balance, ie, iron depletion: In these stages iron stores are low and there is no dysfunction. In stage I negative iron balance, reduced iron absorption produces moderately depleted iron stores. Stage II negative iron balance is characterized by severely depleted iron stores. More than half of all cases of negative iron balance fall into these two stages. When persons in these stages are treated with iron, they never develop dysfunction or disease. (b) Stage III and IV negative iron balance, ie, iron deficiency: Iron deficiency is characterized by inadequate body iron for normal function, producing dysfunction and disease. In stage III negative iron balance, dysfunction is not accompanied by anemia; anemia develops in stage IV negative iron balance. (c) Stage I and II positive iron balance: Stage I positive balance usually lasts for several years with no dysfunction. Supplements of iron and/or vitamin C promote progression to dysfunction or disease. Iron removal prevents progression to disease. Iron overload disease develops in stage II positive iron balance after years of iron overload has caused progressive damage to tissues and organs. Again, iron removal stops disease progression. There are a variety of indicators of iron status. Serum ferritin is in equilibrium with body iron stores.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1990

Synergy of inhibition of DNA synthesis in human bone marrow by azidothymidine plus deficiency of folate and/or vitamin B12?

The effect of azidothymidine (Zidovudine, AZT) on pyrimidine (thymidine, deoxyuridine, and thymidine triphosphate) incorporation into DNA in folate- and/or vitamin B12-deficient and normal human bone marrow cells was studied to investigate whether such vitamin deficiency affects susceptibility to AZT-induced hematologic toxicity. Bone marrow cells from 12 patients were studied: 5 had folate and/or vitamin B12 deficiency; 7 controls included 5 with anemia related to chronic disease and 2 with iron deficiency. At 0.2 microM AZT (3 hr, 37 degrees C), the approximate pharmacologic serum trough level, pyrimidine incorporation into DNA was suppressed by 12 to 19% in folate- and/or vitamin B12-deficient cells and by 16 to 23% in normal cells. At 2.0 microM AZT (3 hr, 37 degrees C), the approximate pharmacologic serum peak level, this was suppressed by 15 to 40% in folate- and/or vitamin B12-deficient cells and by 32 to 47% in controls. Deoxyuridine incorporation into DNA was inhibited significantly greater than thymidine at 2.0 microM AZT (3 hr, 37 degrees C) in both groups. Inhibition of deoxyuridine incorporation was not reversed with methyltetrahydrofolate or vitamin B12. There tended to be less striking suppression by AZT of deoxyuridine incorporation into DNA in bone marrow cells from vitamin B12-deficient patients, which was made more striking by adding vitamin B12. This suggests that some of what passes for "AZT damage" to bone marrow cells may in fact be coincident deficiency of vitamin B12. AZT inhibition of DNA synthesis in 3 hr bone marrow cultures is relatively consistent in a variety of hematologic disorders. As approximately two-thirds of AIDS patients appear to be in negative balance with respect to folate and/or vitamin B12, the fact that AZT-induced inhibition of pyrimidine incorporation into DNA is occurring in cells which may be megaloblastic, i.e., in a state of impaired DNA synthesis, suggests that these cells may be more susceptible to AZT toxicity. The data also support the notion that AZT inhibition results predominantly from termination of DNA chain elongation. Whether folate or vitamin B12 supplementation may partially overcome apparent "AZT inhibition" of DNA synthesis (hematologic toxicity) and whether the benefit of such therapy exceeds the risk will require further study.

Bone Marrow↗
PubMed1990

Low holotranscobalamin II is the earliest serum marker for subnormal vitamin B12 (cobalamin) absorption in patients with AIDS.

In AIDS, as previously found in pernicious anemia (PA), the earliest serum marker of subnormal vitamin B12 (cobalamin) absorption, and therefore of negative B12 balance, is low serum holotranscobalamin II (holo-TC II; B12-TC II) despite normal total serum B12 level, normal serum homocysteine, and normal classic (oral free radio-B12) Schilling test. This may be accompanied by subtle and insidious damage to hematopoietic, immunologic, neuropsychiatric, nutritional and alimentary systems, confirmed by correction on therapeutic trial with B12 therapy. Our studies suggest such selective B12 deficiency occurs in about half of the HIV-1 infected, in part due to frequent depression of B12 absorption by HIV-1 attack on the gastric mucosa and/or opportunistic infection attack on the small bowel, and in part due to a telescoping of the continuum of the stages of negative B12 balance in relation to damage to B12 delivery by the infective and/or systemic disease process. In AIDS, when total serum B12 is normal despite tissue depletion of B12, if the classic Schilling test does not reveal subnormal food B12 absorption, the food Schilling test does. We hypothesize that DNA-synthesizing cells of the hematopoietic, immunologic, neurologic and other systems which have surface receptors solely for holo-TC II, and which have low B12 stores, rapidly become dysfunctional due to B12 deficiency when holo-TC II is low, while cells (such as liver cells) which also have surface receptors for holohaptocorrin (B12-haptocorrin) remain B12-replete. We believe this to be another example of the concept of selective nutrient deficiency in one cell line but not another.

Absorption↗
PubMed1989

Cleavage of folates during ethanol metabolism. Role of acetaldehyde/xanthine oxidase-generated superoxide.

Although folate deficiency and increased requirements for folate are observed in most alcoholics, the possibility that acetaldehyde generated from ethanol metabolism may increase folate catabolism has not been previously demonstrated. Folate cleavage was studied in vitro during the metabolism of acetaldehyde by xanthine oxidase, measured as the production of p-aminobenzoylglutamate from folate using h.p.l.c. Acetaldehyde/xanthine oxidase generated superoxide, which cleaved folates (5-methyltetrahydrofolate greater than folinic acid greater than folate) and was inhibited by superoxide dismutase. Cleavage was increased by addition of ferritin and inhibited by desferrioxamine (a tight chelator of iron), suggesting the importance of catalytic iron. Superoxide generated from the metabolism of ethanol to acetaldehyde in the presence of xanthine oxidase in vivo may contribute to the severity of folate deficiency in the alcoholic.

Acetaldehyde↗
PubMed1989

In vitro DNA synthesis by megaloblastic bone marrow: effect of folates and cobalamins on thymidine incorporation and de novo thymidylate synthesis.

The de novo pathway of thymidylate synthesis (i.e., methylation of dUMP to dTMP) is directly folate dependent and indirectly vitamin B12 (cobalamins) dependent. In deficiency of these vitamins, this pathway is impaired, and exogenous deoxyuridine (dU) fails to suppress adequately in vitro incorporation of [3H]thymidine (3H-TdR) into DNA via the salvage pathway (i.e., abnormal dU suppression). This abnormality is corrected by the addition of folate compounds (analogues) and/or vitamin B12 depending on the nature of the underlying deficiency. We studied the effects of addition of PteGlu, 5-methyl THF (5-CH3-FH4), 5-formyl-THF (5-CHO-FH4), and hydroxy-cobalamin (OH-cbl) on 3H-TdR incorporation into DNA and thymidine kinase activity (salvage pathway), and on [3H]deoxyuridine (3H-dU) incorporation and dU suppression values (de novo pathway) in cultures of normal and megaloblastic bone marrows. The results showed that 3H-TdR incorporation into DNA and the salvage enzyme, thymidine kinase, activity were greater and 3H-dU incorporation into DNA less in megaloblastic cells as compared with normal cells. The addition of folates significantly reduced 3H-TdR incorporation and thymidine kinase activity and enhanced 3H-dU incorporation in folate and vitamin B12-deficient cells except that 5-CH3-FH4 had no effect on vitamin B12-deficient cells. None of these additives had any significant effect on normal cells. This study also showed that the addition of the deficient vitamin(s) to the "control tubes" in the dU suppression test is inappropriate, as these vitamins may at least partially correct the defect in cellular DNA synthesis caused by the deficiencies of these vitamins and may mask these deficiencies in the results of the in vitro correction of the dU suppression abnormalities in mild cases of megaloblastic anemia.

Adolescent↗