A seventy-eight-year-old woman with fever, cough, joint pains, and hypercalcemia.
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Aged↗
Biomedical subjects
M L Freedman
Publications and source records attributed to M L Freedman.
Red cell distribution width, mean corpuscular volume, and transferrin saturation in the diagnosis of iron deficiency.
The usefulness of the red cell distribution width, mean corpuscular volume, and the transferrin saturation in diagnosing iron deficiency anemia were evaluated in a retrospective study of 247 anemic hospitalized patients, many of whom had chronic liver disease. A red cell distribution width greater than 15% had a sensitivity of 71% and a specificity of 54% for iron deficiency as diagnosed by a low serum ferritin or bone marrow examination. A mean corpuscular volume less than 80 femtoliters had a sensitivity of 53% and a specificity of 84%. Transferrin saturation less than 16% had a sensitivity of 61% and a specificity of 86%. Because the sensitivities and specificities of these tests are less than reported in studies of healthier populations, they cannot be relied on for screening for iron deficiency in sick hospitalized patients.
Anemia, Hypochromic↗
Iron deficiency in the elderly.
Iron deficiency in the elderly almost always results from blood loss. The loss of iron can be viewed as occurring in four stages, which are reflected in the different tests used to diagnose iron deficiency. Tests used to diagnose iron deficiency have certain limitations regarding their ability to detect iron deficiency before the overt anaemia occurs. The tests which diagnose iron deficiency most accurately are low serum ferritin and reduced iron staining of a bone marrow aspirate. Because iron is present in many metabolic processes besides the production of haemoglobin, iron deficiency results in a variety of defects which are manifested at biochemical, tissue, and functional levels. Iron is a component of several enzymes in the respiratory electron transport chain. Adequate haem and iron levels are necessary to control cytoplasmic and mitochondrial protein synthesis. Iron deficiency results in tissue defects, including those affecting the gastrointestinal tract, and defects of mitochondria and lymphocytes. Normal iron levels seem to be necessary for normal work capacity. A deficiency of iron, independent of the anaemia, results in reduced exercise capacity that can be measured in both physiological and economic terms. Elderly patients complaining of increased fatigue should therefore be screened for iron deficiency. There is evidence to suggest that iron deficiency may predispose individuals to certain infections. Other information points to the promotion of certain bacterial and parasitic infections after rapid correction of iron deficiency. Thus elderly patients having iron replacement therapy should be followed closely. A deficiency of iron has been shown to result in certain behavioural and learning abnormalities. Iron deficiency has been shown to result in impaired control of body temperature, resulting in an increase in catecholamine levels. The impairment in heat-generating ability was shown to result from reduced conversion of T4 to T3 in the peripheral tissues.
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Cervical cancer screening in women aged 65 and over.
Pap smear screening is an accepted method of detecting cervical dysplasia or malignancy, and use of this test has been shown to reduce the incidence of invasive squamous cervical cancer in young and middle aged women. Conflicting recommendations exist concerning the screening of women over the age of 65, and little information is available concerning the results of screening in this population. Elderly women are routinely omitted from screening, as it is generally believed that they usually refuse testing. This paper reports a study attempting to evaluate the feasibility of screening in women over the age of 64 attending a large urban outpatient geriatric clinic. It demonstrates that pap smear screening is acceptable to this population, particularly if performed by the usual primary care provider. It also confirms previous reports that women in this age group have had very little screening in the past, and that screening uncovers a large number of abnormalities. Of note is the high rate of false positive smears in this population.
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Low serum B12 levels in a hematologically normal elderly subpopulation.
Serum Vitamin B12 levels were determined on 378 patients ranging in age from 56 to 104 years with a median age of 77 for both males and females. A radiodilution method was employed for these determinations. This screening procedure identified 26 patients with low serum B12 levels. Nineteen of these patients had no other symptoms and were hematologically normal. The B12 binding proteins, transcobalamins (TC) I, II, and III were quantitated employing QUSO and DEAE cellulose batch separations. The total number of TC II binding/affinity sites for B12 were elevated in both the normal and low B12 elderly groups. About 17% of the total serum B12 was carried by TC II in the control group while only 4% of the total was carried on TC II in both the normal and low B12 elderly. This was accompanied by an increase in unsaturation in TC II for these two groups. The findings suggest that an alteration in the TC II-B12 delivery system has occurred in the elderly.
Adult↗
Heme and iron metabolism in aging.
Cells from aged animals show a decrease in heme synthesis, an increase in heme degradation, and a maintenance of heme concentration and heme-containing proteins. This raises the possibility that alternate sources of heme are utilized by the old animal to maintain intracellular heme necessary for initiation of protein synthesis. The mechanisms to balance heme and protein synthesis, and cytoplasmic and mitochondrial protein synthesis remain intact with advanced age. Iron remains available to the healthy organism in abundant amounts throughout the life span. The decrease in cellular iron utilization seen with age might conceivably result from availability of heme independent of heme synthesis, as intracellular heme controls the cellular uptake of iron from transferrin. Heme levels in aged cells seem to be maintained via an alternate heme source. The bone marrow in aged animals appears to function adequately as long as there is no stress. Anemia, therefore, should always be considered as a serious sign in illness and never as a normal concomitant of aging.
Aging↗
Gynecologic malignancies of the elderly.
Gynecologic malignancies account for over 20,000 deaths in the United States each year, and over half of these occur in elderly women. If discovered in their early stages, each of these cancers is curable, but increasing age usually correlates with more advanced stage of disease. Except for ovarian cancer, these diseases can be detected in asymptomatic women by simple screening procedures. Although elderly women may be more difficult to treat because of intercurrent medical illness, when they are treated aggressively, age usually has no independent prognostic significance.
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Benzene modulation of liver cell structure and heme-cytochrome P-450 metabolism.
Rats were treated with subcutaneous benzene, 440 mg/kg, for 3 and 14 days (acute and chronic exposure). Their hepatic cell heme and drug metabolizing enzymes as well as cell morphology by electron microscopy were examined. Electron micrographs of hepatocytes from the benzene-treated rats showed disruption of the mitochondrial membranes and mitochondrial structure. The activity of the rate-limiting enzyme of heme synthesis, delta-aminolevulinic acid synthase was increased 1.5-2-fold in both acutely and chronically exposed animals. In the acutely exposed animals, there was a 50% inhibition of the second enzyme of heme synthesis, delta-aminolevulinic acid dehydratase, while in the chronically exposed there was 70% inhibition. The rate-limiting enzyme of heme degradation, heme oxygenase, was increased more than twofold in both sets of animals. Cytochrome P-450 content was increased 77% in the acutely treated and 35% in the chronic. Associated with this increase in cytochrome P-450 content, there was a twofold increase in both arylhydrocarbon hydroxylase and aminopyrine-N-demethylase activities after acute exposure. During chronic exposure, however, there was a return to normal of the aminopyrine-N-demethylase activity and a decline in arylhydrocarbon hydroxylase induction to 1.25 times control. Results from this study indicate that benzene exposure produces adverse effects on mitochondria and heme metabolism. The precise relationships of these disturbances to benzene toxicity are not clear; however the possible role of heme oxygenase and degree of cytochrome P-450 induction are considered. Finally, the alterations of arylhydrocarbon hydroxylase and aminopyrine-N-demethylase activities point to a potential mechanism of differential toxicity from metabolites of benzene.
5-Aminolevulinate Synthetase↗
Folate and vitamin B12 levels in an urban elderly population with chronic diseases. Assessment of two laboratory folate assays: microbiologic and radioassay.
Folate levels of serum and red blood cells (RBC) and vitamin B12 serum levels were investigated in 326 urban chronically ill elderly ambulatory patients and 41 healthy young control subjects. Two laboratory methods were used for investigating the folate levels, the microbiologic assay (MBA) with Lactobacillus casei and radioassay (RA). Serum and RBC samples of 326 patients were tested by the folate MBA and 270 of the same samples by the RIA methods. In the MBA 6.8% of the patients and 12.2% of controls had low levels of folate RBC (less than 200 ng/mL) and 1.8% of patients and 4.8% of controls had low serum folate levels (less than 5 ng/mL). All of the patients with the low folate levels had normal hematologic findings and no clinical symptoms of folate deficiency. In the RIA method, all of the patients and almost all of the control subjects (except one) had normal folate levels. Ten of the patients (3%) had low levels of serum vitamin B12 (less than 200 pg/mL). They were hematologically normal. They had normal Schilling tests and normal vitamin B12 dietary intake. Their RBC folate levels were normal and even somewhat higher. Forty percent of these patients had macular degeneration of the eyes. The data indicate the superiority of the RA method over the MBA and bring into question the accuracy of previous studies. The data furnish further evidence that a low vitamin B12 level in the elderly is not necessarily a true vitamin B12 deficiency and raise the possibility of an association between low B12 serum levels and macular degeneration of the eyes.
Adult↗
Role of heme and iron metabolism in controlling protein synthesis.
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Anemia, Hypochromic↗
Effect of age on rat liver heme and drug metabolism.
Old (24-months) rats have lower activities of hepatic delta-aminolevulinic synthase and the microsomal cytochrome P-450 monooxygenase activities--aminopyrine N-demethylase and aniline hydroxylase--as compared to young (2-months) animals. In contrast, the activity of the heme degradative enzyme, heme oxygenase, is higher in the old rats. Cytochrome P-450 and microsomal heme contents were maintained in the old. When inducibility and inhibition of these enzymes were studied, the old rats responded to the same degree as the young. These results indicate that the ability of the heme synthetic and degradative enzymes to respond to decreasing cellular heme levels is not significantly altered with age. The observations that there is a lower baseline activity of ALA-synthase and good maintenance of microsomal heme and cytochrome P-450 content, in spite of elevated heme oxygenase activity in the old, suggest that, at least in the senescent rat, hepatic heme utilization and degradation are only loosely coupled to heme production. It appears, therefore, that alternate sources of heme for cytochrome P-450 are available in the old animals. Furthermore, it is suggested that the old rat has a baseline change in ALA-synthase, heme oxygenase, and cytochrome P-450 that may be overcome under the appropriate conditions.
5-Aminolevulinate Synthetase↗
Folic acid deficiency in the elderly.
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Nutritional needs of the elderly: debate and recommendations.
Despite all that has been written, little evidence supports the notion that the American diet for the elderly needs major modifications (table 3). Particularly in counseling and assessing the elderly, physicians must keep in mind that whatever technique older patients used to reach their present age is probably better than what we can recommend. In the last analysis, the most sensible nutritional recommendations we can make are to maintain ideal body weight, reduce animal protein, increase complex carbohydrates and fiber, reduce saturated fats and cholesterol, increase calcium intake, and avoid high doses of supplementary nutrients. If available data are any indication, many community-dwelling elderly persons are now making most of these modifications.
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Clinical disorders of iron metabolism in the elderly.
When iron deficiency occurs in the elderly, it is usually due to bleeding and not to nutritional lack or malabsorption. Iron deficiency early in life may lead to irreversible changes (for example, gastric achlorhydria) that are troublesome in later life. The nonhematologic effects of iron deficiency still need to be studied in the elderly. In particular, the role of iron in brain metabolism would seem important in geriatrics. Although it is important to prevent iron deficiency, indiscriminate use of iron could conceivably lead to iron overload. As with many beneficial compounds, patients must be cautioned against the prolonged ingestion of large amounts of iron salts.
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Effect of cimetidine on delta-aminolevulinic acid synthase and microsomal heme oxygenase in rat liver.
Cimetidine is a well known inhibitor of the heme-containing enzyme cytochrome P-450. We have found that it also inhibits delta-aminolevulinic acid synthase (ALA-S) and microsomal heme oxygenase, the rate-limiting enzymes for heme synthesis and heme degradation respectively. Cytochrome P-450 content was decreased but microsomal heme concentration remained unaltered for a period of 30 min after in vivo cimetidine administration to rats. In vitro incubation of cimetidine with each of the above enzymes revealed no direct effect of cimetidine on ALA-S but about 50% inhibition of heme oxygenase and 20% reduction in cytochrome P-450 content. This suggests that a metabolite of cimetidine inhibits ALA-S activity in vivo, while the drug itself or a metabolite inhibits heme oxygenase both in vivo and in vitro. A rise in ALA-S activity seen after its early inhibition and its return to approximate control values after 60 min suggest a reversible inhibition of ALA-S by a metabolite of cimetidine and may correspond to its clearance from the animal. An elevation in microsomal heme content paralleled the rise in ALA-S activity while microsomal heme oxygenase activity returned to only 65% of control value 60 min after cimetidine treatment. Cytochrome P-450 content did not change after its initial decrease, suggesting that irreversible alteration had occurred.
5-Aminolevulinate Synthetase↗
Salivary and serum IgA levels in a geriatric outpatient population.
In two separate studies, specimens of saliva from 57 individuals over the age of 65 years (mean age, 76.7 years) and 37 persons under the age of 40 years (mean age, 28.8 years) were examined for concentrations of IgA as functions of volume, total protein, and electrolyte conductivity; some were also tested for IgG and IgM content. The results show that older persons have higher concentrations of these solutes in their saliva than do younger controls. This suggests that the ability to secrete IgA into saliva does not diminish significantly with aging.
Adult↗