Search PubMed⌕ Search

Biomedical subjects

M Lepage

Publications and source records attributed to M Lepage.

At least 37 records · Page 2Linked to original sources

Hippocampal PET activations of memory encoding and retrieval: the HIPER model.

A meta-analysis of experimentally induced changes in blood flow ("activations") in positron emission tomography (PET) studies of memory has revealed an orderly functional anatomic pattern: Activations in the hippocampal region associated with episodic memory encoding are located primarily in the rostral portions of the region, whereas activations associated with episodic memory retrieval are located primarily in the caudal portions. These findings are based on an analysis of a sample of 54 "hippocampal encoding and retrieval" activations that were culled from an overall database consisting of 52 published PET studies of memory. We refer to this general pattern of rostrocaudal gradient of encoding and retrieval PET activations as the HIPER (Hippocampal Encoding/Retrieval) model. The model suggests a division of memory-related labor between the rostral and caudal portions of the hippocampal formation. Because functional anatomic pattern of encoding and retrieval activation that defines the HIPER model was unprecedented and unexpected, it is difficult to relate the model to what is already known or thought about functional neuroanatomy of episodic memory in the hippocampal regions. The model is interesting primarily because its exploration may yield fresh insights into the neural basis of human memory.

Brain Mapping↗

Frontal lesions increase post-target interference in rapid stimulus streams.

We examined the effects of frontal lesions on the attentional processes surrounding the discrimination of target stimuli by comparing patients with frontal excisions, patients with temporal excisions and controls on target-letter identification in rapid visual streams. Subjects were asked to look at streams of 18-26 letters presented centrally at rates of 6, 8, or 10 letters/sec and to name the two white target letters (T1 and T2) embedded among black letters in each stream. The two target letters were separated by either 0, 2,4, or 6 black letters. Normals and temporals correctly reported T1 at all rates, they showed the expected T2 identification errors peaking 300 msec after T1 at high rate and little T2 interference at lower rates. However, frontals showed T2 interference at the two lower rates and were unable to identify T1 at high rate. The effects observed suggest that an inertia of target discrimination processes contributes to the frontal attention deficits.

Adult↗

Inter-response interference contributes to the sequencing deficit in frontal lobe lesions.

In this study we investigated the contribution of inter-response interference to the sequencing deficit in frontal lobe lesions. We examined inter-response interference in choice sequences through the reduction in inter-response interval produced by stimulus preview when compared with sequences performed without preview. If frontal lobe lesions result in a stronger inter-response interference, the facilitative effect of preview on inter-response interval should be attenuated. We compared nine patients with a frontal excision with nine patients with a temporal excision and nine controls in a task requiring rapid keypress responses to each of five letters in a sequence. In the no-preview condition, the five letters were presented one at a time, immediately following the previous response. In the preview condition, the five letters were presented simultaneously before the response sequence. Patients with a frontal lesion showed slower response times than the other groups. In normal subjects and patients with a temporal lesion, stimulus preview produced the expected reduction of inter-response time and the slowing of sequence initiation. In frontal lesions, however, preview did not reduce inter-response time and exacerbated the slowing of sequence initiation. The results indicate that patients with a frontal lobe lesion show increased interference between adjacent responses as well as a sequence initiation problem.

Adult↗

Controlled release low dose medroxyprogesterone acetate (MPA) inhibits the development of mammary tumors induced by dimethyl-benz(a) anthracene in the rat.

Medroxyprogesterone acetate (MPA) is well recognized to have beneficial effects for the treatment of advanced breast cancer which are comparable to those achieved with other forms of endocrine therapy. Using mammary tumors induced in the rat by dimethylbenz(a)anthracene (DMBA) as a model, we have studied the possibility that low dose MPA could prevent the development of these tumors. Single subcutaneous injection of Depo-Provera (crystalline suspension of MPA) or MPA encapsulated in biodegradable microspheres of 50:50 poly[DL-lactide-co-glycolide] was given 7 days before oral DMBA. While 63% of intact animals developed palpable mammary tumors within 85 days after DMBA administration, tumor incidence decreased to 28% and 23% in animals who had received 30 mg and 100 mg of Depo-Provera, respectively. The same amounts of MPA delivered in microspheres caused a further decrease in tumor incidence to respective values of 7% and 6%. Average tumor area, on the other hand, decreased from 4.89 cm2 in intact rats to about 0.75 (0.57-0.88) cm2 and approximately 0.20 (0.14-0.22) cm2 in the Depo-Provera and microsphere-treated groups, respectively. Using the 50:50 formulation of poly[DL-lactide-co-glycolide] designed to release MPA at a constant rate for a 4-month period, the serum MPA concentration at 3 months was measured at 4.99 +/- 0.43 ng/ml. Such data suggest that administration of a low dose controlled-release formulation of MPA in 50:50 poly[DL-lactide-co-glycolide] microspheres could well be an efficient and well tolerated approach for the prevention of breast cancer in women.

9,10-Dimethyl-1,2-benzanthracene↗

[Treatment of and survival after epidermoid cancer of the esophagus in the department of Finistère between 1984 and 1988 (716 cases)].

The incidence of esophageal cancer in the French county of Finistère is among the highest in France (26.7/10(5) for males). The authors analyzed the survival rates for squamous cell carcinomas from data of the Finistère tumor registry in order to describe different prognostic groups of patients using the multivariate Cox model. From 1984 to 1988, 716 patients with esophageal squamous cell carcinomas were registered in an overall population of 828,000 residents: 675 males and 41 females. Survival was calculated using the actuarial method. Six hundred and seventy five patients died before the point date (31 Dec 1989). Only one patient was lost to follow-up. The actuarial survival rates of all patients were 89 +/- 1% at 3 months, 68 +/- 2% at 6 months, 37 +/- 2% at one year, 12 +/- 1% at 3 years and 6 +/- 1% at 5 years; median survival was 9.1 +/- 0.4 months. Survival was significantly related to cancer size, tumor extension and surgical contraindications. In the Cox model, age, cancer size, surgical contraindications, year of diagnosis were independent prognostic predictors. There was a significant increase in survival rates after 1986: median survival was 8.1 +/- 0.4 months between 1984 and 1986 and 10.1 +/- 0.5 months between 1987 and 1988. Patients treated by curative resection had higher actuarial survival rates (median survival 22.5 +/- 4.1 months) than patients who underwent palliative resection (median survival 11.3 +/- 1.2 months). In patients with cancer managed surgically, the prognostic predictors were tumor size, curative vs palliative surgical resection and association with chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate.

Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12-dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co-glycolide] microspheres in the same DMBA-induced tumor model. The present data show that single subcutaneous injection of a 4-month controlled-release formulation of biodegradable 50:50 poly[DL-lactide-co-glycolide] microspheres containing 10 mg of MPA giving serum levels of 3.14 +/- 0.32 ng/ml (8.12 +/- 0.83 nM) MPA causes a maximal or near-maximal 60% inhibition of tumor growth measured 56 days later. Such data suggest that controlled-release formulations giving constant and low blood levels of MPA could be used for the treatment of breast cancer in women. Such a low concentration of MPA should avoid the side effects observed with the high doses of the compound.

9,10-Dimethyl-1,2-benzanthracene↗

Localization of plutonium retention in the small intestine of the neonatal rat, guinea pig, baboon and macaca after Pu-citrate ingestion.

The retention of Pu-citrate in the gastrointestinal wall was compared at similar post ingestion times after ingestion at 2 days of age by rats and guinea pigs and at 1 to 34 days by neonatal primates. The small intestine was the main site of the Pu retention in all species. In rats and primates, most of the Pu was retained in the distal ileum, whereas in guinea pigs it was more homogeneously distributed. In the rats, Pu was retained in the epithelial cells on villi, but in the guinea pigs and primates it was confined to the macrophages under the epithelial cells in the lacteal region.

Animals↗

In vitro studies of fatty acid metabolism in vitamin B6 deficient rats.

The oxidation of [1-14C]palmitate, [1-14C]linoleate, and [1-14C]arachidonate as well as their incorporation into lipids was investigated in vitamin B6 deficient rats using liver slices and isolated mitochondria. In experiments on fatty acid oxidation in liver slices, we observed a decrease in the production of 14CO2 from radioactive palmitate and linoleate, but not from arachidonate. In the case of mitochondria, we detected no difference between the deficient rats and the controls with linoleats; however, there was an increase in the oxidation of palmitate in the deficient rats as compared to the controls. Experiments on the incorporation of radioactivity into lipids showed an increase in radioactivity from [1-14C]palmitate and [1-14C]linoleate in the triglyceride, phospholipid and cholesterol fractions of deficient rats. In the case of [1-14C]arachidonate, no difference was observed between the two groups of rats. These experiments showed that major changes occurred in metabolism of palmitate and linoleate and strongly suggested that the decrease in the arachidonate content previously observed in rat tissues could not be explained by alteration in the metabolism of this fatty acid.

Animals↗

[Value of extra-intracranial anastomosis: based on a series of 65 cases].

The authors describe the results obtained in a series of 65 patients following extra-intracranial cortical anastomosis. The best indications for this procedure are transitory ischemic accidents which cannot be approached by the direct cervical route. Cases of prolonged or definitive vascular accidents and more especially localized lesions also gave valuable results but these depend upon the condition of the cerebral parenchyma which must be carefully evaluated.

Brain Ischemia↗

A comparison of fatty acid patterns of arterial plasma, pericardial fluid and cardiac lymph in dog.

The fatty acid composition of cardiac lymph and pericardial fluid in anesthetized open-chest dogs, was analysed and compared with that of arterial plasma. The fatty acid content of triglyceride (TG) and total fatty acid fractions of pericardial fluid and cardiac lymph was significantly lower than that of plasma. On the other hand, free fatty acid (FFA) concentrations of pericardial fluid, cardiac lymph and plasma were not significantly different. The FFA fraction of cardiac lymph contained relatively more stearic acid and less oleic acid whereas, in plasma, the FFA fraction contains less myristic acid. The data are consistent with the hypothesis that endothelial permeability is a limiting factor for the transvascular exchanges of large molecules such as TG and that the FFA distribution in intersititial spaces may have been modified by the contribution of fatty acids from endogenous cardiac reserves or from the hydrolysis of plasma TG.

Animals↗

[Effect of pyridoxine deficiency on fatty acid metabolism in the rat].

We have studied the effect of pyridoxine deficiency on rat liver fatty acid synthetase using acetyl-1-14C-CoA. We have observed no significant difference in the synthetase activity between the deficient and ad libitum control rats. From in vivo experiments with palmitate-1-14C, linoleate-1-14C or arachidonate-1-14C, we noted an increase in the oxidation of all fatty acids in the deficient animals. Studies with the same tracers on their incorporation rate into liver triglycerides and phospholipids showed an increase in the rate of incorporation of palmitate and linoleate within lipids of deficient rats, but no significant difference was seen with arachidonate.

Acetyl Coenzyme A↗

Study of the natural antihistamine-like substance in bile in mammals.

A natural antihistamine substance (NAS) present in bile has been investigated. It was found that the antihistamine activity was not due to proteins, lipids, pigments, or amino acids. On ion exchange chromatography and thin-layer chromatography, this activity was associated with bile acids. Many bile acids could, in varying degrees, inhibit this histamine induced guinea pig ileum contraction, desoxycholic acid being the most potent. However NAS activity could be separated from bile acids and their conjugates using a different solvent system. Furthermore, NAS showed a higher antihistamine activity than bile acids. This substance seems to be responsible for 15-20% of the activity of whole bile. The substance has not yet been identified.

Animals↗

Effects of pyridoxine deficiency on the composition of plasma and liver fatty acids in rats fed low and high fat diets.

A study was made of the effect of pyridoxine deficiency on the fatty acids of liver and plasma in rats fed diets containing 1, 10, or 20% fat. Both ad libitum-fed and pair-fed control rats were used. In pyridoxine deficiency, arachidonic acid decreased with a concomitant increase in linoleic acid. Incubation of liver slices with [1-14C]acetate showed no significant alteration of fatty acid synthesis in pyridoxine-deficient rats fed 1 or 10% fat when compared with the ad libitum-fed control rats, but revealed a marked increase in cholesterogenesis compared with either control group. Incubations with [1-14C]linoleate resulted in no differences in the synthesis of arachidonate between the experimental and the ad libitum-fed control rats. Incubations with [5,6,8,9,11,12,14,15-3H]arachidonate showed decreased incorporation of this fatty acid in total liver lipids in pyridoxine-deficient rats compared with ad libitum fed control rats. We concluded that the diminution in arachidonate observed in liver lipids of pyridoxine-deficient rats does not result from a lower conversion of linoleate into arachidonate, but possibly from an increased degradation of this fatty acid.

Animals↗