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Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

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

Selective interactions of cytochromes P-450 with the hydroxymethyl derivatives of 7,12-dimethylbenz[a]anthracene.

Competition between a hydroxylated metabolite and the parent polycyclic aromatic hydrocarbon (PAH) for metabolism at cytochromes P-450 may result in the generation of hydroxylated dihydrodiol epoxides. The effectiveness of the competition between 7-hydroxymethyl-12-methylbenz[a]anthracene (7HOMMBA) or 12-hydroxymethyl-7-methylbenz[a]anthracene (12HOMMBA) and 7,12-dimethylbenz[a]anthracene (DMBA) is highly dependent on the form(s) of cytochrome P-450 in the microsomes. The inhibitory effects of exogenously added 7HOMMBA or 12HOMMBA on DMBA metabolism were 30- to 50-fold greater in 3-methylcholanthrene (MC)-induced rat liver microsomes (Ki = 0.4 microM) compared to either uninduced or phenobarbital (PB)-induced liver microsomes (Ki = 14 and 11 microM, respectively). Similarly, product inhibition of total DMBA metabolism by metabolites generated in situ was significant only in MC-induced liver microsomes (Ki' = 2.5 microM). Metabolism of 7HOMMBA in these microsomes was strongly restricted by an unusual substrate inhibition derived from the inhibitory binding of a second molecule of 7HOMMBA. This same phenomenon was observed with reconstituted cytochrome P-450c but not with PB-induced or uninduced microsomes. Complex formation by binding of DMBA, 7HOMMBA, and 12HOMMBA to purified P-450c reconstituted in phospholipid micelles was determined by optical spectroscopy and fluorescence quenching. Binding affinities of both the 7HOMMBA and 12HOMMBA (Kd = 95 and 110 nM, respectively), were 2.5-fold higher compared to that of DMBA (Kd = 265 nM). These results provide a first demonstration that hydroxylation of a PAH can lead to preferential metabolism through an increased affinity for cytochrome P-450.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Diagnosis and quantitation of pulmonary arteriovenous malformations by factor analysis.

The diagnosis of a pulmonary arteriovenous malformation (AVM) was made by performing a computer-assisted first-pass cardiopulmonary imaging procedure using Tc-99m pertechnetate and processing the image information using factor analysis. This analytical technique is capable of separating partially overlapping structures by automatically extracting factors with different temporal behavior (time-activity curves) which correspond to functional areas without anatomic constraint. This procedure was accomplished successfully despite the presence of four-chamber enlargement, mitral stenosis and regurgitation, tricuspid regurgitation, chronic obstructive pulmonary disease and pulmonary hypertension. The magnitude of the right-to-left shunt resulting from the AVM was quantitated using both the factor analysis data and an independent Tc-99m MAA computer-assisted imaging procedure. Both methods gave comparable values.

Arteriovenous Malformations↗
PubMed1986

[Arteriographic data in chronic ischemia of the hand. Study of 62 cases].

The arteriograms of sixty-two patients with chronic ischemia of the hand and fingers were reviewed. Twelve patients were considered to have Raynaud's disease. Thoracic outlet syndrome caused ischemic symptoms in thirteen patients. Arteriosclerosis obliterans affected twenty-two patients. The signs of arteriosclerosis are described including irregular constrictions, multiple occlusions and the corkscrew pattern of the collateral arteries. The differential diagnosis includes thromboangiitis obliterans and collagen vasculitis.

Adolescent↗
PubMed1985

Early and delayed clinical cardiotoxicity of doxorubicin.

Five hundred thirty-four evaluable patients with breast cancer were treated with a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide. The total planned dose of doxorubicin was 300 mg/m2 in patients with Stage II or III disease, and 450 mg/m2 in patients with isolated recurrences. The median time interval from start of adjuvant therapy to time of analysis was 68 months. Two percent had congestive heart failure associated with doxorubicin. Fifteen patients showed myocardial dysfunction attributed to either additional treatment with potentially cardiotoxic drugs for recurrent disease or other causes. The incidence of congestive heart failure was 1% in patients treated with up to 300 mg/m2, and 4% in patients who received 450 mg/m2 of doxorubicin. The median time interval from the end of doxorubicin to development of congestive heart failure was 1 month (range, 0-33 months). None of the 326 patients who have been followed 3 or more years (162 followed 5 or more years) since completion of doxorubicin therapy have developed congestive heart failure which was considered to be related from that therapy.

Adult↗
PubMed1983

Structure-activity relationships in the interactions of alkoxymethylenedioxybenzene derivatives with rat hepatic microsomal mixed-function oxidases in vivo.

Following in vivo administration to rats of equimolar amounts of a series of 4-n-alkoxymethylenedioxybenzene (AMDB) derivatives, hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activities, total cytochrome P-450 levels, and AMDB metabolite-cytochrome P-450 spectral complex (455 nm) formation were well correlated in parabolic relationships with pi, the hydrophobic constant of the n-alkoxy substituent. Each of these parameters increased progressively over control values with increasing carbon chain length of the alkoxy substituent, passed through an optimal value in compounds containing five or six carbon atoms, and subsequently decreased with the higher homologues. AHH activity was highly correlated in linear relationships with total (complexed plus uncomplexed) cytochrome P-450 content and intensity of the 455-nm spectral complex. Aminopyrine N-demethylase activities in microsomes from AMDB-treated rats were not well correlated with cytochrome P-450 levels or spectral complex formation. AMDB metabolite-ferricytochrome P-450 complexes varied considerably in their relative ease of displacement following treatment with 2-n-heptylbenzimidazole, those derived from the n-butoxy to n-hexoxy derivatives being particularly stable toward the displacer. The results are discussed in relation to the possible mechanisms involved in the interactions of methylenedioxyphenyl compounds with cytochrome P-450 and drug oxidation.

Animals↗
PubMed1977

[The present state of hypotension (author's transl)].

The study was made of the recent literature on controlled hypotension and its place in modern anaesthetic practice. The effects of the different techniques and drugs are outlined in this paper. The results of investigation revealed that the circulation of heart, brain, liver, and kidneys is able to tolerate a wide range of deviation of blood pressure. Hypotension induced by high doses of halothane alone, which used to be considered as an adequate measure, has recently been shown to cause such serious side-effects that it can no longer be recommended. Halothane lowers blood pressure almost exclusively by means of a reduction of the contractility of the heart muscle. Ganglionic blocking agents alone should not be used either because of their depressing effect on the heart; moreover their hypotensive effects are hard to control. The sole exception is trimetaphan but it produces other severe side-effects such as liberation of histamine. On the other hand ganglionic blocking agents combined with halothane can be recommended. The combined administration of these drugs allow an easy control of hypotension and the side effects are minimal. Only sodium-nitroprusside meets all the requirements of a hypotensive drug. It operates selectively in a peripheral vasoplegic manner without effecting the cerebral centres. Regarding the heart, no side-effect is known apart from tachycardia; cardiac output is not altered. The metabolism of sodium-nitroprusside requires precaution in dosage, as degradation takes place via the toxic compounds of cyanide. Therefore liver disease and disturbances in vitamin B12 utilisation are regarded as contraindications for the use of nitroprusside. That is also the reason why a maximum allowable dose of 10-15 gamma/kg body weight and minute should not be exceeded. Prophylactic administration of vitamin B 12a (hydroxocobalamin) should be considered in every case when nitroprusside is used.

Cardiac Output↗
PubMedDate not supplied

The breast self-examination practices of high risk women: implications for patient education.

The breast self-examination (BSE) behavior of 142 women referred to a large cancer center with malignant or benign breast disease was investigated. The women were interviewed about their BSE practices and variables that may have influenced their BSE behavior. Those reporting prior BSE practice were asked to demonstrate their breast examination to a trained nurse, who rated their performance against a set of standard criteria. Although it might be assumed that these women have had more opportunity to become educated about BSE, results showed the ratings of the women's performances were uniformly poor. Less than half reported having formal instruction by a medical professional. This is of particular consequence considering that those women taught by a doctor or nurse performed significantly more BSE steps than did those taught in other ways. Women who were encouraged to do BSE by friends or relatives also performed significantly more steps. Based on the study findings, specific recommendations are made, which can be applied to the improvement of BSE educational programs.

Attitude to Health↗