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Biomedical subjects

J D Cook

Publications and source records attributed to J D Cook.

At least 127 records · Page 7Linked to original sources
PubMed1986

Cerebrospinal fluid ferritin levels in screening for meningism.

To evaluate the potential diagnostic value of the ferritin concentration in cerebrospinal fluid (CSF), measurements were performed with an immunoradiometric assay in 23 control patients and in 65 patients with various neurologic disorders. The geometric mean ferritin level of 3.5 micrograms/L in controls was approximately 10% of the level in normal serum with an upper cutoff level of 10 micrograms/L. Only modest elevations in CSF ferritin concentration were observed in patients with viral meningitis and in those with various non-infectious neurologic disorders. On the other hand, marked elevations ranging between 27 and 322 micrograms/L (geometric mean, 90 micrograms/L) were observed in patients with bacterial or fungal meningitis. Results of the study indicate that CSF ferritin levels are a valuable adjunct in the early evaluation of patients presenting with meningism.

Cell Count↗
PubMed1986

A serum ferritin assay for prevalence studies of iron deficiency.

A specialized serum ferritin assay has been developed for the detection of iron deficiency in epidemiologic studies. An enzyme immunoassay (EIA) was employed to eliminate the need for radioisotopes. The problem of low sensitivity inherent with the EIA for serum ferritin was eliminated by the use of monoclonal immunologic reagents. The working range of the assay is 1-100 micrograms/L with a sensitivity of 0.5 micrograms/L. Excellent agreement in serum ferritin levels was observed between the present method and the two-site immunoradiometric assay (IRMA), while the variability at low ferritin concentrations was significantly less with the EIA. Because only 10 microliter of serum is required for each assay, duplicate measurements can be performed on a single capillary tube of blood. When an automatic microtiter plate reader for optical density measurements is used, 80-100 duplicate determinations can be completed by one technologist in a single working day.

Anemia, Hypochromic↗
PubMed1986

The liabilities of iron deficiency.

Iron has been recognized as a potent hematinic since the inception of hematology as a clinical discipline. Even ancient civilizations believed in the beneficial effects of medicinal iron. Nevertheless, the precise functional liabilities of iron lack remain the subject of continuing debate. The consequences of iron deficiency, particularly from a socioeconomic standpoint, are especially important in light of its high global prevalence. A recent review of the literature indicates that approximately 30% of the estimated world population of nearly 4.5 billion are anemic, and at least half of these, 500 to 600 million people, are believed to have iron deficiency anemia.

Adult↗
PubMed1986

Plasma ferritin determination as a diagnostic tool.

Plasma ferritin is a secretory component of intracellular ferritin synthesis. In normal persons its amount reflects the size of iron stores. A decrease to less than 12 mug per liter indicates iron deficiency. Increased iron stores are associated with an increased plasma ferritin level. Various other conditions, however, can increase the plasma ferritin concentration including increased metabolism, inflammation, tissue damage and neoplastic disease. The use of the plasma ferritin determination in diagnosing iron overload depends on excluding these other causes, leaving storage iron as the only explanation for the increased plasma ferritin. It is then necessary to establish the parenchymal nature of the iron overload by showing an elevated transferrin saturation and, if elevated, the more definitive liver biopsy should be done.

Ferritins↗
PubMed1986

Estimates of iron sufficiency in the US population.

Traditionally the iron status of a population is assessed by estimating the prevalence of iron deficiency anemia. This approach is inadequate in countries where the diet is heavily fortified with iron because it conveys no information about the iron-replete segment of the population. In the present study iron status of a US adult population was evaluated using data collected in the second National Health and Nutrition Examination Survey (NHANES II). Body iron was estimated in each of 2,829 individuals from measurements of hemoglobin concentration, serum ferritin, transferrin saturation, and erythrocyte protoporphyrin. When individuals between 18 and 64 years of age were divided on the basis of sex and menstrual status, body iron reserves were normally distributed and averaged 309 mg in women 18 to 44 years, 608 mg in women 45 to 64 years, and 776 mg in men 18 to 64 years. The dispersion of storage iron in these groups was similar, with standard deviations of 346, 372, and 313 mg, respectively. The prevalence of iron deficiency anemia was surprisingly low, ranging from only 0.2% in adult men to 2.6% and 1.9% in pre- and postmenopausal women, respectively. Epidemiologic methods that examine iron status in the entire population assume importance in light of evidence that in certain segments of the US population, iron deficiency anemia is now less common than the homozygous state for hereditary hemochromatosis.

Adult↗
PubMed1985

Myophosphorylase deficiency impairs muscle oxidative metabolism.

We studied oxidative metabolism during bicycle exercise in 4 patients with myophosphorylase deficiency. Maximal oxygen uptake (VO2max) was low (14.0 +/- 1.4 ml X kg-1 X min-1, mean +/- SE) compared with that in normal subjects (37.7 +/- 1.9; n = 12) and patients with myalgia (24.9 +/- 1.8; n = 10). Carbohydrate oxidation, as estimated by the respiratory exchange ratio (R), was low relative to workload (max R, mean +/- SE: McArdle's disease, 0.96 +/- 0.02; normal subjects, 1.13 +/- 0.02; myalgia, 1.09 +/- 0.02). Intravenous glucose administration increased maximal oxygen uptake about 20% in those with McArdle's disease, but both VO2max and R remained lower than in control subjects. These findings suggest that the capacity for dynamic exercise in McArdle's disease is limited by the availability of oxidative substrate, and indicate that blood glucose is unable to substitute fully for muscle glycogen as an oxidative fuel. We also found that exercise cardiac output (Q) was excessive relative to oxygen uptake in affected patients (delta Q/delta VO2, mean +/- SE: McArdle's disease, 11.6 +/- 1.7; normal subjects, 4.8 +/- 0.2; myalgia, 5.6 +/- 0.2). This hyperkinetic circulation in exercise may serve to increase the delivery of blood-borne oxidative substrate to working muscle.

Adolescent↗
PubMed1985

Soy protein products and heme iron absorption in humans.

Dual radioiron tags were used to measure both heme and nonheme iron absorption simultaneously from meat-containing meals in 76 healthy male volunteers. Partial substitution of beef with soy flour reduced the availability of nonheme iron but improved the percentage absorption of heme iron significantly (27 to 59% rise). In contradistinction three other powerful inhibitors of nonheme iron absorption, bran, tea, and desferrioxamine, had no appreciable effect on heme. Ascorbic acid (100 mg and 1000 mg in separate experiments) improved nonheme iron uptake markedly but also failed to alter the assimilation of heme. These studies demonstrate that the deleterious effects on iron nutrition of substituting soy protein for beef are partially offset by improved availability of the remaining heme iron as well as by an increase in the nonheme iron content of the meal.

Adolescent↗
PubMed1985

Muscle fatigue in McArdle's disease studied by 31P-NMR: effect of glucose infusion.

In muscle phosphorylase deficiency (McArdle's disease) there is an abnormally rapid fatigue during strenuous exercise. Increasing substrate availability to working muscle can improve exercise tolerance but the effect on muscle energy metabolism has not been studied. Using phosphorus-31 nuclear magnetic resonance (31P-NMR) we examined forearm muscle ATP, phosphocreatine (PCr), inorganic phosphate (Pi) and pH in a McArdle patient (MP) and two healthy subjects (HS) at rest and during intermittent maximal effort handgrip contractions under control conditions (CC) and during intravenous glucose infusion (GI). Under CC, MP gripped to impending forearm muscle contracture in 130 s with a marked decline in muscle PCr and a dramatic elevation in Pi. During GI, MP exercised easily for greater than 420 s at higher tensions and with attenuated PCr depletion and Pi accumulation. In HS, muscle PCr and Pi changed more modestly and were not affected by GI. In MP and HS, ATP changed little or not at all with exercise. The results suggest that alterations in the levels of muscle PCr and Pi but not ATP are involved in the muscle fatigue in McArdle's disease and the improved exercise performance during glucose infusion.

Adenosine Triphosphate↗
PubMed1984

Iron deficiency.

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Adolescent↗
PubMed1984

Iron absorption from legumes in humans.

Iron bioavailability in a variety of legumes was determined by radioisotopic measurements of iron absorption in human subjects. Soybeans, black beans, lentils, mung beans, and split peas were prepared as soups, labeled by the extrinsic tag method, and served to fasting subjects. Mean percentage absorption was uniformly low, ranging from 0.84 to 1.91%. Differences in absorption between the means were not statistically significant. The results indicate that these five commonly eaten legumes are all poor sources of dietary iron.

Absorption↗
PubMed1984

An evaluation of monoclonal antibodies for serum ferritin measurements.

Serum ferritin measurements have become an important laboratory parameter of iron status in prevalence surveys. Because the use of monoclonal antibodies may reduce variability and facilitate standardization, the present study was undertaken to determine whether their performance is comparable to conventional immunological reagents in an immunoradiometric assay for serum ferritin. When evaluated as the capture antibody for the solid phase, no differences in dose response curves were observed between monoclonal reagent and whole antiserum. When monoclonal reagent was used as the radiolabeled indicator antibody, the dose response curves were also similar to those obtained with affinity-purified polyclonal reagent although between-assay variability was somewhat higher with monoclonal antibody. In measurements of serum ferritin in patients with a wide range of iron status, no consistent differences were observed in the results from assays using monoclonal antibody and those of the conventional reagent. These preliminary studies indicate that the performance of monoclonal antibodies in a conventional ferritin assay is comparable to conventional immunological reagents.

Antibodies, Monoclonal↗
PubMed1984

High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid.

The concentration of lead in blood, serum, cerebrospinal fluid, and urine was measured in patients with neurological disease and in control subjects including cases of plumbism. A plot of blood lead versus serum lead resembles the familiar curves of blood lead versus either free erythrocyte porphyrin or urinary delta-aminolaevulinic acid in that serum lead is constant up to a blood lead concentration of 40 micrograms/dl (2 mumol/l) and rises steeply thereafter. The serum lead concentrations yield renal clearances in the range 5-22 ml/min in agreement with values obtained with radiolead on man and predicted from animal studies. The lead content of cerebrospinal fluid is consistently less than that of serum, averaging 50% of the serum concentration for blood leads of less than 20 micrograms/dl (1 mumol/l) but rising to 80-90% in cases of plumbism. Patients with motor neurone disease could not be distinguished from those with other neurological diseases on the basis of the lead content of their serum or cerebrospinal fluid.

Humans↗
PubMed1984

Metabolic control of cardiac output response to exercise in McArdle's disease.

During dynamic exercise cardiac output (Q) normally increases approximately 5 liters per liter of increase in O2 uptake (Vo2) (i.e., delta Q/delta Vo2 approximately equal to 5), indicative of a tight coupling between systemic O2 transport and utilization. We studied four patients with muscle phosphorylase deficiency (McArdle's disease) in whom Q was normal at rest, but delta Q/delta Vo2 was 14.1 +/- 1.3 during bicycle exercise. Procedures designed to alter the availability of substrates were employed to test the hypothesis that the increased delta Q/delta Vo2 is linked to the abnormal metabolic state of skeletal muscle. Fasting plus prolonged moderate exercise was used to increase the availability of plasma free fatty acid (FFA) and resulted in a normalization of delta Q/delta Vo2 (5.3 +/- 0.4). Hyperglycemia (70% above control levels) partially normalized delta Q/delta Vo2. Nicotinic acid lowered plasma FFA concentration and dramatically increased delta Q/delta Vo2 (4.6 to 13.7) when administered after fasting plus prolonged exercise in one patient. Glucose infusion after nicotinic acid administration markedly lowered delta Q/delta Vo2. The results support the hypothesis and suggest that the metabolic state of skeletal muscle, possibly via activation of muscle afferents, participates in the regulation of systemic O2 transport.

Adolescent↗
PubMed1984

The effect of high ascorbic acid supplementation on body iron stores.

The level of assimilation of dietary iron is believed to have an important influence on iron status. To examine the effect of enhancing the availability of dietary iron on iron balance, 17 adult volunteer subjects were given 2 g of ascorbic acid daily with meals for 16 weeks. Serum ferritin levels before and after the study averaged 46 and 43 micrograms/L, respectively, indicating a negligible effect on iron stores. When vitamin C supplementation was continued for an additional 20 months in five iron-replete and four iron-deficient subjects, serum ferritin determinations again failed to indicate any significant effect of the vitamin C on iron reserves. These findings were not explained by intestinal adaptation to the enhancing effect of the vitamin, because radioisotopic measurements of nonheme iron absorption showed no reduction in the enhancing effect of 1 g of ascorbic acid after four months of megadoses of vitamin C. It is concluded that altering the availability of nonheme dietary iron has little effect on iron status when the diet contains substantial amounts of meat.

Absorption↗