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Biomedical subjects

A Lacroix

Publications and source records attributed to A Lacroix.

At least 19 recordsLinked to original sources

Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing's syndrome.

BACKGROUND: Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known. METHODS: We studied a 48-year-old woman with Cushing's syndrome, nodular adrenal hyperplasia, and undetectable plasma corticotropin concentrations in whom food stimulated cortisol secretion. RESULTS: Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone. The cortisol concentrations increased in response to oral glucose (4-fold increase) and a lipid-rich meal (4.8-fold increase) or a protein-rich meal (2.6-fold increase), but not intravenous glucose. The infusion of somatostatin blunted the plasma cortisol response to oral glucose. Intravenous infusion of gastric inhibitory polypeptide (GIP) for one hour increased the plasma cortisol concentration in the patient but not in four normal subjects. Fasting plasma GIP concentrations in the patient were similar to those in the normal subjects; feeding the patient test meals induced increases in plasma GIP concentrations that paralleled those in plasma cortisol concentrations. Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin. In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producting or aldosterone-producing adenomas responded to corticotropin but not to GIP. CONCLUSIONS: Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder.

Adrenal Glands

[Teaching the patient to comply with his treatment. A training course for physicians].

A teaching programme on verbal doctor-patient interaction is presented, an often neglected topic. Based on taped recordings of their own consultations the participants discussed in seminars of some ten hours the problems that arose during the conversation with patients. Difficulties were noted with listening to the patient, to the understanding of his real needs, to the use of adequate language and the evaluation of the patients' perception. A guideline lists all points to be considered in a conversation about a prescription of medication. The review of ones own conversations is an extremely efficacious stimulus for education pointing out deviations from the prescription scheme to the doctor concerned that he has himself elaborated.

Communication

[The dialogue of prescribing. Gaps and possibilities for improvement with a brief interactive seminar].

The recordings of 24 medical consultations at an outpatient clinic show that residents can explain quite well the rationale and modalities of treatment. While being founded on secure knowledge in the biomedical domain fewer bases were encountered regarding the affective side of doctor-patient interactions. In this respect residents often neglect important elements for a prescription during consultation such as reiterations of complaints, mention of the diagnosis, explanation of the patients' role for control of therapy and repetition of specific points of the conversation in order to check the patients' understanding. Control tests three months after a special training seminar revealed that important progress was realized in all deficient domains.

Communication

[Swiss educational experience with a prescription dialogue in ambulatory medicine].

Teaching seminars on the topic of medical prescriptions were organized in Switzerland with the cooperation of 34 independent practitioners and residents from outpatient clinics in Basel, Geneva, Neuchâtel and Berne. Taped recordings from 230 consultations revealed strong points (biomedical aspects) and weaknesses (insufficient appraisal of the affective side and the participation of patients) in such conversations. These observations permit to compare the five groups of doctors participating in this study.

Ambulatory Care

[Better listening, better information, better teaching. Lessons of our incompetence].

Short excerpts of conversations held during medical consultations permit analysis of a whole range of poorly adapted attitudes and thus demonstrate the possibility for improvement of affective contact, confidence and efficacy. It is recommended to: listen more attentively, avoid interruptions, excuses, simplifications, interpretations and premature information and to learn to repeat the flow of thoughts of the patient; inform more adequately without usage of medical terminology, abstain from confused explications, frequent change of subject, imprecision and attitudes forcing the patient into an inferior role; improve teaching of the patient by proposing distinct goals and by inviting him to find solutions to his problems by learning from errors, this without patronising and under consideration of the attitude of the patient towards his disease.

Attention

Effect of dietary restriction on hepatic vitamin A content in aging rats.

The size and number of fat-storing cells (FSC), considered to be the main liver storage site of vitamin A, as well as hepatic vitamin A content, were studied in aging female Sprague-Dawley rats subjected soon after weaning to dietary restriction (R), that is, 60% of food consumed by their ad libitum-fed controls (A). In A or R rats, the FSC index (number of cells per 1000 hepatocytes) and volume density (% of hepatic volume) were increased significantly at 24-27 months compared with the younger age groups. The lipocyte index and volume density were also found to be significantly higher, after the first year, in R rats when compared to corresponding age-matched A controls. An increase in total vitamin A content was also noted with age in both groups. R rats exhibited higher retinol, retinyl ester, and total retinoid content than their corresponding controls, but the differences were statistically significant only at 12-14 and 24-27 months. These results indicate that, during aging, dietary restriction markedly increases vitamin A content in liver tissue, a change that may be relevant to the beneficial effect of this dietary manipulation on liver function.

Aging

Biochemical characteristics of cytosolic and particulate forms of protein tyrosine kinases from N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma.

Protein tyrosine kinase (PTK) activities in methyl nitrosourea (MNU)-induced rat mammary carcinoma has been investigated by using poly (glu: tyr; 4:1) as an exogenous substrate. The PTK activity of the mammary carcinoma was almost equally distributed between the particulate and soluble (cytosolic) fractions at 110,000 X g. The activity of the particulate enzyme was stimulated by non-ionic detergent Triton X-100 by about 2-fold whereas the detergent had no effect on the cytosolic form. More than 60% of the particulate enzyme could be solubilized by 5% Triton X-100. Although, both particulate and cytosolic PTKs catalyzed the phosphorylation of several tyrosine containing synthetic substrates to various degrees, poly (glu: tyr; 4:1) was the best substrate (apparent Km. 0.7 mg/ml). Both forms of enzymes utilized ATP as the phosphoryl group donor, with an apparent Km of 40 microM. Among various divalent cations tested, Co2+, Mn2+ and Mg2+ were able to fulfill the divalent cation requirement of both forms of the PTKs. All these cations exerted biphasic effects on the kinase activities, however, Mg2+ was the most potent cation. Agents such as epidermal growth factor, insulin and platelet derived growth factor which stimulate their respective receptor-PTK activities were without effect on PTK activities of mammary carcinoma. On the other hand, though heparin and quercetin inhibited both enzyme activities in a concentration dependent manner, the particulate form was more sensitive to inhibition than the cytosolic form. These data indicate that MNU-induced rat mammary carcinoma expresses both particulate and cytosolic forms of PTKs and that there are significant differences in the properties of the two forms of PTKs. Differential effects of some agents on mammary carcinoma PTKs suggest that these enzymes may be acutely regulated in vivo and could play an important role in mammary carcinogenesis.

Animals

Family aggregation of cancer of the prostate in Quebec: the tip of the iceberg.

Cancer of the prostate is one of the most common cancers among males in North America. Although some causative factors have been suggested by several surveys, the etiology of this common cancer is poorly understood. In a case-control study of prostatic cancer in Greater Montreal, 21 of 140 patients with prostatic cancer (15.0%) gave a positive family history of the same cancer, as compared with two cases among 101 (2.0%) population-based controls. This indicates about an eightfold difference in occurrence of cancer of the prostate among first-degree family members of the case group with an odds ratio (OR) of 8.7 and 95% CI, 2.00-38.17. In this report we present the pedigrees of three families (two cases and one control) with four pathologically confirmed cases of cancer of the prostate in each family. This data suggest that a familial predisposition to prostatic cancer may become apparent in later decades of life. In these family aggregations, in addition to the genetic factors, environmental factors may also play an important role in the etiology of the same cancer among family members.

Aged

Effects of retinoic acid on the concentrations of radioactive metabolites of retinol in tissues of rats maintained on a retinol-deficient diet.

The effects of feeding retinoic acid for 2 and 6 days on the metabolism of labeled retinol in tissues of rats maintained on a vitamin A deficient diet was studied. The metabolites of retinol were analyzed by high performance liquid chromatography. Feeding retinoic acid for 2 days significantly reduced the blood retinol and retinyl ester levels without affecting the vitamin A content of the liver. In intestine and testis the content of labeled retinoic acid was decreased significantly by dietary retinoic acid. Addition of retinoic acid to the diet for 6 days resulted, in addition to decreased blood retinol and retinyl ester values, in an increase in the retinyl ester values in the liver. The accumulation of retinyl ester in the retinoic acid fed rat liver was accompanied by an absence of labeled retinoic acid. Kidney tissue was found to contain the highest levels of labeled retinoic acid, retinol, and retinyl esters; dietary retinoic acid did not alter the concentrations of these retinoids in the kidney during the experimental period. Since kidney retained more vitamin A when the liver vitamin A was low and also dietary retinoic acid did not affect the concentrations of radioactive retinoic acid in the kidney, it is suggested that the kidney may play a major role in the production of retinoic acid from retinol in the body.

Animals

Inhibition of growth of established N-methyl-N-nitrosourea-induced mammary cancer in rats by retinoic acid and ovariectomy.

Retinoids are effective in the prevention of N-methyl-N-nitrosourea-induced mammary carcinoma; retinoids and hormonal therapy exert synergy in cancer prevention. In this study, we examined the effects of the dietary supplementation with all-trans retinoic acid (RA) alone or in combination with ovariectomy on the growth of established N-methyl-N- nitrosourea-induced mammary carcinomas in rats. In the first experiment, animals (n = 13) were entered in each of the following treatment groups when their tumors reached 2 cm in diameter: 1, control diet; 2, RA 300 mg/kg diet; 3, ovariectomy (OVX); 4, RA 300 mg/kg diet plus OVX. Animals were sacrificed after 28 days of therapy. In the RA-supplemented animals, tumor progression was less than in the control group without signs of toxicity as assessed by total and individual tumor surface area and weight, and animal weight. OVX produced tumor regression that was not enhanced by the addition of RA. In a second experiment, RA 65- and 130-mg/kg diets were dissolved in corn oil with antioxidants prior to mixing to the diet to improve biodisponibility. This resulted in overall stabilization of tumor growth by RA addition to the diet at either of the 2 doses utilized; the addition of RA 65 mg/kg diet did not modify tumor regression induced by OVX. In conclusion, the dietary supplementation with RA decreased the progression or stabilized the growth of the majority of tumors and only rarely (6%) induced tumor regression; no additive or synergistic effects were found with the combination of RA and ovariectomy.

Animals

Metabolism of retinol and retinoic acid in N-methyl-N-nitrosourea-induced mammary carcinomas in rats.

This study was conducted to examine the in vivo uptake and metabolism of natural retinoids by N-methyl-N-nitrosourea-induced mammary carcinomas. In this study, endogenous retinol and retinyl esters were present in normal mammary epithelial cells, but were undetectable in N-methyl-N-nitrosourea-induced mammary carcinomas in rats as determined by high-pressure liquid chromatography. No differences were found in plasma levels of retinol, in liver retinyl esters, or total content of vitamin A between tumor-bearing and control animals. Administered labeled retinol was taken up and esterified by normal mammary epithelial cells. Tumor-bearing rats were given injections i.p. of either [3H]retinol or [3H]retinoic acid. Radioactivity increased progressively with time in liver and other tissues except in breast tumor, where the uptake fluctuated over the 8 days after the injection of [3H]retinol; in mammary tumors practically no metabolism of [3H]retinol occurred, while in other tissues extensive esterification was detectable. In contrast, in animals given injections of [3H]retinoic acid, the uptake and metabolism of the label in the breast tumors paralleled with those found in other tissues. Neither the activity of acyl coenzyme A:retinol acyl transferase nor the activity of retinyl ester hydrolase was altered in the mammary tumor compared to the normal mammary gland. On the other hand, a significant decrease in the retinal oxidase activity was found in tumor tissue compared to normal mammary tissue. Since no esterification of [3H]retinol occurred in vivo despite the presence of acyl coenzyme A:retinol acyl transferase activity, it is possible that a specific defect in the cellular uptake of retinol may exist in N-methyl-N-nitrosourea-induced mammary carcinomas.

Acyltransferases

Daily and seasonal variations in plasma LH and testosterone concentrations in the adult male hedgehog (Erinaceus europaeus).

A double-antibody heterologous radioimmunoassay (RIA) was developed to measure plasma LH values in hedgehogs. This RIA system used anti-rat LH serum and rabbit LH (AFP-559B) for radioiodination and as standard. The accuracy of the method was evaluated and indicated the ability to detect various relative concentrations of LH in plasma. The minimum detectable dose was 0.2 ng/ml. The intra- and inter-assay coefficients of variation were 4.2 and 7.9% respectively. Biological tests, e.g. effect of castration, effect of castration + testosterone implant and GnRH administration, confirmed that this method was suitable to determine subsequent changes in pituitary gonadotrophic activity in the hedgehog. LH concentrations were determined in blood samples obtained during 1 year: (a) each month, at 4-h intervals during 24 h, from different groups of unanaesthetized animals fitted with a catheter and (b) twice a month, under a light anaesthesia, from the same group of 6 animals. During the year: (1) the range of LH change was narrow (minimum values congruent to 0.25 ng/ml and maximum values congruent to 2.00 ng/ml); (2) the 24-h LH patterns did not exhibit any daily rhythm; (3) a clear annual rhythm was observed with the highest values from February to April and the lowest values in October and November. LH decreased rapidly at the end of summer and increased progressively from December to February, during hibernation. In these experiments, it was not possible to determine the characteristics of LH release patterns in the hedgehog but individual profiles indicated clearly the episodic secretion of LH, particularly during the highest pituitary activity period. During the year, a close relationship between the seasonal cycles of plasma LH and testosterone was observed.

Animals

Properties of retinal-oxidizing enzyme activity in rat kidney.

An enzyme activity which converts retinal to retinoic acid was found in the cytosol of rat kidney. The oxidation of retinal was pH-, temperature-, time- and protein-dependent. Under the assay conditions employed, the oxidase activity had an apparent Km of 125 microM toward all-trans retinal. n-Propylgallate, butylated hydroxytoluene and quinacrine inhibited the reaction. The inhibition caused by quinacrine can be partly reversed by FAD. p-Hydroxymercuribenzoate, a sulfhydryl cross-linking agent, was a potent inhibitor. 4'-(9-Acridinylamino)methanesulfon-anisidide, an inhibitor of aldehyde oxidase, inhibited the reaction by 77% at a concentration of 3 mM. All-trans retinal reversed the inhibition caused by acetaldehyde and 2-aminobenzaldehyde. Retinol inhibited the reaction, but retinoic acid did not. The specific activity of the enzyme was increased by vitamin A deficiency. These data indicate that retinal-oxidizing enzyme activity found in the kidney is a sulfhydryl flavoprotein and its activity is dependent on the vitamin A levels of the tissues.

Animals