Biomedical subjects
Publications and source records attributed to J Lacour.
Chiral TRISPHAT anions behave as efficient asymmetric hosts controlling with high efficiency the configuration of a cationic dicobalt(II) triple helicate--de up to 82%.
[structure in text] Aromatic ortho-disulfone derivatives are readily accessible from diiodide precursors by Cu(I)-mediated reactions with sodium sulfinate salts. The sulfone substituents adopt C(2)-symmetric enantiomeric conformations (lambda and delta) as evidenced by X-ray structural analysis and (1)H and (31)P NMR on chiral bis(sulfonyl)veratrol derivatives and hexacoordinated tris(benzenediolato)phosphate anions. Slow dynamic conformational isomerism (DeltaG(++) > or = 19.8 kcal mol(-1)) was detected in solution.
C(2)-Symmetry hexacoordinated phosphorus BINPHAT anion-of configuration controlled by a BINOL ligand-can be prepared readily in a one-pot process and behaves as an efficient NMR chiral shift agent and chiral inducer onto monomethinium dyes (CD, (1)H NMR).
Tetradentate 1,2-bis[4-(4'-methyl-2,2'-bipyridyl)]ethane ligand (3) and Fe(NH4)2(SO4)2.6H2O combine in a 3:2 ratio to form the racemic helicate [Fe2L3]4+ (4), as reported by Elliott et al. We now show that the enantiomeric purity of 4 can be efficiently measured by 1H NMR by the use of the TRISPHAT (1) salt as a chiral shift reagent. Large differences in chemical shifts (deltadeltadelta of up to 0.3 ppm, 20% [D6]DMSO in CD3CN) are observed between the enantiomers of 4 upon addition of [nBu4N][delta-1]. The resolution of 4 by asymmetric extraction was attempted: addition of an organic solution of [cinchonidinium][delta-1] salt (2 equiv) to an aqueous solution of helicate 4-(SO4)2 led, after vigorous stirring, to the extraction of the homochiral diastereomer [P-4][delta-1]4 into the organic layer along with the precipitation of the heterochiral diastereomer [M-4][delta-1]4 at the interface (diastereomeric ratio>49:1 for both processes). An enantioenriched fraction of [P-4][SO4]2 remained in the aqueous layer. To obtain only two fractions of resolved helicate and develop this procedure into an efficient resolution protocol, four equivalents of [cinchonidinium][delta-1] salt were used as the resolving agent. Chemically and diastereomerically pure [P-4][delta-1]4 and [M-4][delta-1]4 helicate salts were then obtained in excellent yields.
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With a median follow-up of 14 years, the combination of polyadenylic-polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.
PURPOSE: To analyze, both by a retrospective and prospective study design, the relationship of maximal oxygen consumption (VO2max) and physical activity (PA) to upper respiratory tract infections (URTI) symptomatology in elderly subjects. METHODS: 61 (33 men and 28 women) healthy and weight-stable active elderly volunteers aged 66-84 yr participated in the study. PA was evaluated by a questionnaire QAPSE (Questionnaire d'Activite Physique Saint-Etienne) and expressed by two QAPSE activity indices: MHDEE (mean habitual daily energy expenditure) and sports activity (daily energy expenditure corresponding to leisure time sports activities). Log books for daily recording of URTI symptomatology were used in prospective design. RESULTS: In a 1-yr retrospective study a significant correlation was found between number of weeks with URTI per year and Sports activity index (r = -0.27, P = 0.037). In a prospective 12-month follow-up, the number of episodes per year and number of days with URTI per year were significantly negatively associated with sports activity index (r = -0.29, P = 0.022 and r = -0.26, P = 0.041, respectively). CONCLUSIONS: In healthy active elderly subjects the symptomatology of URTI over long periods of time is inversly related to energy expenditure utilized during moderately intensive physical exercise.
A 63-year-old man presented suddenly and spontaneously an isolated painless oculomotor palsy of the nerve abducens. As no etiology could be suspected a head MRI was performed. It showed a T1 hypersignal of the intracavernous segment of the internal carotid artery with a double-lumen pattern typical of dissection. The patient was treated with aspirin and recovered from clinical symptoms in 10 weeks. A control MRI was performed 3 months after the onset of symptoms and showed the regression of the images of dissection. There was no ischemic lesion of the brain. This case underlines the diversity of the symptoms of spontaneous dissections of cervicocephalic arteries, especially absence of pain, palsies of cranial nerve that are not always limited to lower cranial nerve, and existence of dissections limited to the intracranial segment of the carotid artery. It suggests the interest of MRI in the diagnosis of isolated oculomotor nerve palsies.
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In a double blind study, patients with operable carcinoma of the colon and the upper rectum, who have undergone a macroscopically complete resection of their tumor, were randomized to receive either (i) polyadenylic-polyuridylic acid (AU), one i.v. injection of 60 mg (in 50 ml of solution) once a week for 6 weeks, or (ii) a placebo (P) one i.v. injection of 50 ml of a saline solution with the same schedule. From January 1983 to December 1986, 288 patients were enrolled: 145 in AU group and 143 in P group. The main clinical and pathological characteristics were equally distributed throughout the two groups. There was a significant difference (P < 0.02) in the overall survival (OS) between the two groups, in favor of the P group. The 5-year OS rate was 68% (SD = 4%) in the AU group versus 81% (SD = 3%) in the P group. Thus, AU as a single adjuvant, appears to be ineffective and therefore has no indication in the treatment of colorectal carcinoma.
In this study, patients with operable breast cancer T2 or T3, treated by mastectomy + axillary dissection and with invaded axillary nodes (N+), were randomized to receive either: 1) postoperative locoregional and pelvic radiotherapy (RX) and Poly(A).Poly(U) (AU), 60 mg IV once a week for 6 weeks, or 2) CMF (cyclophosphamide 100 mg/sqm P.O. on days 1-14, methotrexate 40 mg/sqm IV on day 1 and 8, fluorouracil 600 mg/sqm IV on day 1 and 8; monthly cycle, for 6 months. Between March 1982 and December 1985, 517 patients were enrolled, 257 of whom were treated by RX + AU and 260 with CMF. The main clinical, pathological and prognostic characteristics were equally distributed in the two groups. The present analysis was conducted after a mean follow-up of 69 months (S.D. = 13). There was no significant difference in overall survival (OS) between the two groups (test adjusted by center and menopausal status); the five-year OS rate was 74% in the RXAU group and 77% in the CMF group. Relapse-free survival (RFS) was significantly higher (p = 0.05) in the RXAU group compared to the MCF group; the five-year RFS rates were 57% and 46% in the two groups respectively. This short, well-tolerated combined RXAU treatment appears to be as efficient as CMF and might offer an alternative to chemo- or hormonotherapy, in case of contraindications to these treatments.
The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer.
A randomized trial was conducted at the Institut Gustave-Roussy (IGR) between 1972 and 1980 comparing tumorectomy and breast irradiation with modified radical mastectomy. One hundred and seventy-nine patients with an infiltrating breast carcinoma up to 20 mm in diameter at macroscopic examination were included: 88 had conservative management, and 91 a mastectomy. All patients had a low-axillary dissection with immediate histological examination. For the patients with positive axillary nodes, a complete axillary dissection was undertaken. Overall survival, distant metastasis, contralateral breast cancer and locoregional recurrence rates were not significantly different between the two treatment groups.
A multivariate analysis on 1195 patients with operable breast cancer and histologically positive axillary nodes treated by mastectomy and complete axillary dissection at the Institut Gustave-Roussy between 1958 and 1978 suggests a beneficial effect of treatment of the internal mammary chain (IMC) on the risks of death and distant metastasis for the patients with medial tumors. For these patients, surgical IMC dissection and post-operative irradiation have similar effects on both the risk of death and of distant metastasis. For the patients with lateral tumors, no beneficial effect of the treatment of the IMC on these two risks was observed. Postoperative irradiation to the IMC, axilla, chest wall and supraclavicular nodes significantly decreases the risk of locoregional recurrences independent of the tumor site and surgical management of the lymph nodes.
A randomized trial of polyadenylic-polyuridylic acid (Poly(A).Poly(U) given as an adjuvant in the treatment of operable breast cancer, has included 300 patients of the Institut Gustave-Roussy from September 1972 to December 1979; 145 patients were allocated to conventional treatment alone and 155 to conventional treatment plus Poly(A).Poly(U). Reviews after mean periods of follow-up of 50 and 87 months were previously published. The present review performed after a mean follow-up period of 111 months confirmed a significant increase in the overall survival of patients with invaded nodes treated with Poly(A).Poly(U). The best results were achieved in the subset of patients with up to three affected nodes who showed a significant increase of both overall and relapse-free survival. The benefit seemed to be greater in postmenopausal women (P = 0.07). Present status of other ongoing trials of adjuvant Poly(A).Poly(U) is presented.
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From September 1963 to January 1968, 243 patients with operable breast cancer were included in a randomized trial designed to compare classical radical mastectomy (RM) alone to extended mastectomy (EM), i.e. RM plus internal mammary dissection. One hundred and seventeen patients underwent RM, and 126 EM. After a mean follow-up time of 20 years, no significant differences were observed between the two treatment groups for overall survival, for the relapse-free survival rates, nor for distant metastasis, or locoregional recurrence rates. From a regression model, significant interactions were found between risk of death, EM, and both nodal status and site of the tumour. When compared to RM, EM significantly decreased the risk of death for patients with internal or medial tumour and positive axillary nodes (P = 0.05). No beneficial effect of EM was observed for any of the other patients; on the contrary, EM seemed to increase the risk of death for the patients with external tumour and negative axillary nodes (P = 0.07).