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Biomedical subjects

C Myers

Publications and source records attributed to C Myers.

At least 91 records · Page 5Linked to original sources

Declining adrenal androgens: an association with bone loss in aging women.

Bone loss in aging women is a major contributing factor to the onset of osteoporosis. To determine whether a decline in adrenal androgen output might be important in the loss of bone with age, we studied a highly selected group of 14 women, average age 70, and measured adrenal androgens in relationship to trabecular bone density. Dehydroepiandrosterone sulfate (DHEAS) levels were used as a marker of adrenal sex steroid output while quantitative, computerized tomography was used to determine trabecular bone density. Our results showed that both bone density (r = -0.69, P less than 0.01) and DHEAS levels (r = -0.68, P less than 0.01) declined with age, and that DHEAS was positively correlated with bone density (r = 0.66, P = 0.01). These data emphasize the association of declining adrenal sex steroid production with declining bone density during the process of aging.

Adrenal Cortex↗

Anthracyclines.

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Animals↗

Assessment of the risk of vertebral fracture in menopausal women.

The decision to institute prophylaxis in women with menopausal osteopenia is hampered by the absence of quantitative criteria for appraising the risk of fracture in the individual. We have developed standards for assessing the risk of fracture by relating the prevalence of atraumatic vertebral compression fractures to bone density in sixty-five menopausal women, forty-nine to ninety-two years old. To define the upper limit of the spectrum of bone density, we also studied thirty-one young women, seventeen to twenty-two years old. The density of trabecular bone in a vertebral body was determined by quantitative computed tomography and expressed in terms of milligrams per milliliter of dipotassium hydrogen phosphate. Twenty-five of the menopausal women exhibited at least one fracture (range, one to six fractures), and forty had no fracture. The bone density ranged from -9 to sixty-nine milligrams per milliliter in those with fractures and from twelve to 122 milligrams per milliliter in those without a fracture. The densities in the young women averaged 173 milligrams per milliliter and ranged from ninety-five to 248 milligrams per milliliter. The percentage of subjects with fractures increased as the bone density decreased. It was zero per cent in women with a density of seventy milligrams per milliliter or more, 38 per cent in women with a density between fifty and less than seventy milligrams per milliliter, 71 per cent in those with a density between thirty and less than fifty milligrams per milliliter, and 82 per cent in women with a density of less than thirty milligrams per milliliter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Role of iron in adriamycin biochemistry.

Adriamycin forms a chelate with Fe(III) that exhibits complex redox chemistry. The drug ligand is able to directly reduce the bound Fe(III) with the concomitant production of a one-electron oxidized drug radical. This Fe(II) can reduce oxygen to hydrogen peroxide and cleave the peroxide to yield the hydroxyl radical. In addition, the drug X Fe complex can catalyze the transfer of electrons from reduced glutathione to molecular oxygen to yield superoxide, hydrogen peroxide, and hydroxyl radicals. The adriamycin X Fe complex binds to DNA to form a ternary drug X Fe X DNA complex, which is also able to catalyze the thiol-dependent reduction of oxygen and the formation of hydroxyl radical from hydrogen peroxide. As a consequence of this chemistry, the adriamycin X Fe complex can cleave DNA on the addition of glutathione or hydrogen peroxide. Although less well defined, the adriamycin X Fe complex can bind to cell membranes and cause oxidative destruction of these membranes in the presence of thiols or hydrogen peroxide.

Cell Membrane↗

Thiol-dependent DNA damage produced by anthracycline-iron complexes. The structure-activity relationships and molecular mechanisms.

Doxorubicin (Adriamycin) and daunomycin analogs have been examined for their ability to chelate iron and catalyze the oxidative cleavage of DNA. The results show that the C-11-hydroxyl group is essential for iron binding and DNA damage. Thus, the iron complexes of doxorubicin, daunomycin, carminomycin, and 4-demethoxydaunomycin are potent redox catalysts capable of reducing molecular oxygen in the presence of physiologic concentrations of glutathione. They are also effective catalysts of hydroxyl radical formation from hydrogen peroxide. With the exception of daunomycin, generation of hydroxyl radical from hydrogen peroxide is stimulated by greater than 200% by DNA addition. Analogs that lack the C-11-hydroxyl group are relatively inefficient at oxygen reduction, hydroxyl radical formation, and DNA cleavage. The potencies of the anthracycline analogs tested in the H2O2-dependent DNA cleavage reaction correlated well with their relative cardiac toxicities.

Animals↗

Oxidative destruction of DNA by the adriamycin-iron complex.

The 2:1 adriamycin-Fe(III) complex is able to bind to DNA and to catalyze its oxidative destruction. The binding of the drug-metal complex to DNA is indicated by characteristic spectral changes which are different from those seen with adriamycin intercalation and by the propensity of the drug-metal complex to precipitate DNA. Furthermore, intercalated adriamycin appears not to be available for iron binding. The resulting ternary complex is quite stable: it is not disrupted by incubation in the presence of EDTA and can be isolated by using Sephadex G-50 column chromatography. Disruption of the ternary complex requires vigorous conditions (extraction with phenol at 60 degrees C). The adriamycin-iron complex in free solution has the capacity to catalyze the reduction of oxygen by thiols. The DNA-bound drug-metal complex preserves this capacity over a wide range of complex/DNA ratios. As a consequence of this thiol-dependent oxygen reduction, DNA is cleaved. This thiol-dependent DNA cleavage has been shown to require hydrogen peroxide as an intermediate product. These results have led us to propose that the thiol-dependent DNA cleavage reaction has two stages involving (1) reduction of oxygen leading to hydrogen peroxide and then (2) peroxide-dependent DNA cleavage. An unusual property of this reaction is that the cleavage is not random but gives rise to a defined 2300 base pair fragment.

Chemical Phenomena↗

Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors.

Previously, 5-bromodeoxyuridine (BrdUrd) has been shown to be an effective radiosensitizing agent in rapidly dividing cells. As part of a Phase I/II study to evaluate BrdUrd as a radiosensitizer in gliomas, the pharmacology was studied in eight patients. BrdUrd was infused using an i.v. route as a 12-hr constant infusion each day for as long as 14 days. BrdUrd steady-state arterial levels are described for three different infusional rates: 1.6 mumol/sq m/min (350 mg/sq m/12 hr) produced a steady-state arterial level of 0.7 microM; 3.2 mumol/sq m/min (700 mg/sq m/12 hr) resulted in 2.1 microM; 5.9 mumol/sq m/min (650 mg/sq m/6 hr) showed a level of 3.9 microM. Because of myelosuppression, the highest tolerable dose for this intermittent long-term infusional therapy with BrdUrd appears to be 700 mg/sq m/12 hr. Contrary to the nonlinear pharmacokinetics of thymidine, 5-fluorouracil, and 5-fluorodeoxyuridine described previously, BrdUrd shows linear behavior in the range studied. BrdUrd still has promise as a radiosensitizer for gliomas in humans, but an alternative means of safe delivery into the carotid artery is needed. Because of an estimated 11- to 16-fold-higher local concentration, use of the intraarterial route could deliver optimum levels of BrdUrd to the tumor with minimal systemic toxicity.

Brain Neoplasms↗

Salt restriction in hypertensive patients. Comparison of advice, education, and group management.

The purpose of this study was to identify the best of three methods of treating hypertensive outpatients in order to minimize dietary sodium levels and thereby decrease the need for antihypertensive drugs. Forty-eight outpatients with hypertension were randomly assigned to three treatment programs: (1) advice; (2) an intensive educational program; and (3) small-group management plus feedback. This last program had a problem-solving format in which patients shared ideas and provided mutual support for dietary change. Only these group management patients were told the results of their sodium determinations. In a one-year study, group management plus the feedback to patients of information on the sodium content of their urine was more effective in decreasing dietary sodium intake than advice or an intensive educational effort.

Adult↗

Katacalcin: a new plasma calcium-lowering hormone.

A second potent plasma calcium-lowering peptide, katacalcin (PDN-21), flanks calcitonin within the human calcitonin precursor. Plasma katacalcin was present in 57 healthy volunteers. Concentrations were higher in males than in females and approximately equimolar with calcitonin. Plasma katacalcin doubled within 5 min of calcium infusion. Plasma katacalcin was markedly raised in 20 patients with medullary carcinoma of the thyroid. Measurement of plasma katacalcin concentrations may prove useful in the diagnosis and follow-up of this condition. Katacalcin, like calcitonin, may be involved in both plasma calcium regulation and skeletal maintenance and thus may prove useful in the treatment of bone disease.

Adolescent↗

Alcohol-related advertisements in a college newspaper.

The college newspaper is a powerful socializing force on the university campus. Within the general context of a university-based Alcohol Abuse Prevention Project, the present investigation examined alcohol related advertising in a college newspaper at one southern university. Ads were categorized into those: (1) promoting the responsible use of alcohol, (2) promoting the irresponsible use of alcohol, and (3) having a neutral content. Results indicated that a great deal of alcohol-related advertising was presented in this publication, and the majority of advertising did not promote responsible use of the beverage. The potential role of the community-oriented professional as an intervention strategist is discussed.

Advertising↗