All-optical nuclear quantum sensing using nitrogen-vacancy centers in diamond.

Solid state spins have demonstrated significant potential in quantum sensing with applications including fundamental science, medical diagnostics and navigation. The quantum sensing schemes showing best performance under ambient conditions all utilize microwave or radio-frequency driving, which poses a significant limitation for miniaturization, energy efficiency, and non-invasiveness of quantum sensors. We overcome this limitation by demonstrating a purely optical approach to coherent quantum sensing. Our scheme involves the 15N nuclear spin of the Nitrogen-Vacancy (NV) center in diamond as a sensing resource, and exploits NV spin dynamics in oblique magnetic fields near the NV's excited state level anti-crossing to optically pump the nuclear spin into a quantum superposition state. We demonstrate all-optical free-induction decay measurements-the key protocol for low-frequency quantum sensing-both on single spins and spin ensembles. Our results pave the way for highly compact quantum sensors to be employed for magnetometry or gyroscopy applications in challenging environments.

Human hypertension caused by mutations in WNK kinases.

Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.

[Sexual dysfunction after curietherapy and external radiotherapy of the prostate for localized prostate cancer]. / Dysfonctions sexuelles après curiethérapie et radiothérapie externe de la prostate pour cancer de la prostate localisé.

OBJECTIVES: Knowing the importance of sexuality items in the choice by the patient of the modality of treatment of localized prostate cancer, we aimed at reviewing and updating the effects of prostate radiotherapy and brachytherapy on sexual functions. METHOD: A PubMed search was done using the keywords: prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, ejaculation and orgasm. RESULTS: After both radiotherapy and brachytherapy, sexual troubles occur progressively, the onset of occurrence of erectile dysfunction being 12-18 months after both treatments. Even though the pathophysiological pathways by which radiotherapy and brachytherapy result in erectile dysfunction have not yet been fully clarified, arterial damage and exposure of neurovascular bundle to high levels of radiation seem to be two main causes of erectile dysfunction after radiotherapy and brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of erectile dysfunction. Another important factor following radiotherapy is the treatment modality. Not many data about ejaculation and orgasm after radiation treatments have been published yet. Recent data show that most of the population treated by brachytherapy conserves ejaculation and orgasm after treatment, even if a majority describe reduction of volume and deterioration of orgasm. Patients need to be correctly informed on the possible sequela of radiotherapy and brachytherapy on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for erectile dysfunction.

Mimicking Electromagnetic Wave Coupling in Tokamak Plasma with Fishnet Metamaterials.

This paper reports a fishnet hyperbolic metamaterial that mimics the electromagnetic properties of magnetically confined plasma. These electromagnetic properties are strongly anisotropic and different from any conventional material, therefore cannot be mimicked by bulk materials. The structure is made of a stack of thin copper grids spaced by Rohacell foam. We numerically and experimentally show that this kind of structuration matches well the properties of a homogeneous plasma. This solution breaks a long-lasting bottleneck and will accelerate the development of high-frequency heating systems to be used in nuclear fusion.

[Partial delegation to radiation therapists of the control by cone beam CT of prostate positioning]. / Délégation partielle du contrôle quotidien de position de la prostate par tomographie conique aux manipulateurs en électroradiologie médicale.

PURPOSE: Intensity modulated radiotherapy for prostate cancer involves daily monitoring of the positioning of the prostate, possible with cone beam CT (CBCT). It allows increased accuracy compared to readjustments but induces an increase in the time dedicated to these medical checks. The aim of the study was to evaluate the possibility of delegation of this task to the radiation therapists by comparing their readjustments to the doctors. PATIENTS AND METHODS: Five consecutive patients treated with radiation for prostate cancer (76Gy) were analysed. All had a daily CBCT for position control. The movements of the prostate relative to the bony part, the positional variations of the prostate measured by the radiation therapists and the doctors and medical time required to analyse imagery (filling of the rectum and bladder and perform a recalibration) were measured. RESULTS: One hundred seventy-six CBCT were analysed or 980 steps in the three axes. The movements of the prostate relative to bony part were respectively at least 5mm in 19%, 7% and 3% in the anterior-posterior, upper-lower and right-left axes. Changes readjustments between radiation therapists and doctors were in 95% of cases at the most 4mm in the anterior-posterior and upper-lower axis, and 3mm in the left-right axis. The time for medical use of the CBCT averaged 8min 40 [4 to 22min]. CONCLUSION: The daily readjustment on the prostate using CBCT may be delegated to radiation therapists with acceptable concordance of less than 4mm for 95% of measurements. An initial and ongoing training will ensure treatment safety.

Cerebroprotective effect of angiotensin IV in experimental ischemic stroke in the rat mediated by AT(4) receptors.

Recent studies have reported potential roles of angiotensins in an adaptative physiological mechanism of protection against cerebral ischemia-induced neurological damages. In the present study, we examined the protective role of angiotensin IV (AngIV) in a rat model of embolic stroke induced by intracarotid injection of calibrated microspheres (50 microm). Internal carotid infusions of increasing doses of AngIV (0.01, 0.1 and 1 nmol/0.1 mL saline) dose dependently decreased mortality, neurological deficit and cerebral infarct size at 24 hours. With the highest dose of AngIV, mortality was reduced from 55 % in saline infused controls to 10 % (p=0.003), neurological deficit was reduced from 3.8 +/- 0.3 to 1.4 +/- 0.3 , (p<0.0001) and cerebral infarct size at 24 hours was decreased from 432 +/- 26 mm(3) to 185 +/- 19, (p=0.0001). The AT(4) antagonist divalinal-AngIV (10(-9) mol/0.1 mL), or pretreatment with L-NAME (10(-7) mol/0.1 mL), both completely abolished the protective effect of AngIV (1 nmol). The AT(2) antagonist PD123319 (10(-7) mol/0.1 mL) partially prevented the protective effect of AngIV on the neurological score. Sequential cerebral arteriographies revealed that AngIV induced a redistribution of blood flow to the ischemic areas within minutes. These results suggest that pharmacological doses of AngIV are protective against acute cerebral ischemia by triggering an AT(4)-mediated, NO-dependent intracerebral hemodynamic mechanism.

[Salvage concomitant chemoradiation therapy for non-metastatic inflammatory breast cancer after chemotherapy failure]. / Chimioradiothérapie concomitante des cancers du sein inflammatoire, non métastatiques, non répondeurs à une chimiothérapie première.

PURPOSE: To evaluate the surgical possibility following concomitant chemoradiotherapy for inflammatory breast cancer, after unsucessful neoadjuvant chemotherapy. PATIENTS AND METHODS: The data from ten patients with inflammatory breast cancer treated between 1996 and 2010 by concomitant chemoradiotherapy after unsucessful neoadjuvant chemotherapy were analysed. All patients had an invasive carcinoma. All patients received a neoadjuvant chemotherapy, including anthracyclin, six patients received taxan and one received trastuzumab. Radiotherapy was delivered to the breast and regional lymph nodes in all patients at a dose of 50Gy; a boost of 20Gy was delivered to one patient. Concomitant chemotherapy was based on weekly cisplatin for six patients, on cisplatin and 5-fluorouracil the first and last weeks of radiotherapy for four patients. RESULTS: The median follow-up for all patients was 44 months. Mastectomy was performed in nine patients. Two- and 5-year overall survival rates were respectively 70 % and 60 %. Median local recurrence delay was 5 months; six patients died (all from cancer), seven developped metastasis. Grade 1 and 2 epithelite was respectively observed in six and two patients, grade 2 renal toxicity in three patients, grade 2 neutropenia in one patient. CONCLUSION: Concomitant chemoradiotherapy for inflammatory breast cancer after unsucessful neoadjuvant chemotherapy may control the disease in some patients and lead to mastectomy. These results have to be confirmed through a multicentric study with more patients.

Treatment results, survival and prognostic factors in 109 inflammatory breast cancers: univariate and multivariate analysis.

Between 1978 and 1987, 109 patients without metastatic disease were treated by induction chemotherapy for inflammatory breast cancer (IBC) or "neglected" locally advanced breast cancer (LABC): 62 patients had a clinical history of rapidly growing tumours (doubling time < or = 4 months) and inflammatory signs; conversely, the 47 neglected patients had local inflammation with a longer history of LABC. 103 patients were fully evaluable. All patients received the same induction chemotherapy with doxorubicin, vincristine, cyclophosphamide and 5-fluorouracil. After six cycles, locoregional treatment was by radiotherapy if a complete or nearly complete response had been obtained, and total mastectomy, with pre or postoperative radiotherapy, in other cases. The chemotherapy after local treatment comprised of six cycles for LABC and 12 cycles for IBC (six without doxorubicin). With a median follow-up of 120 months, the median overall survival (OS) time was 70 months as against 45 months for disease-free survival (DFS). No difference was observed for OS and DFS between LABC and IBC. The regional recurrence rate was 24% (15% for radiotherapy alone). 20 factors of potential prognostic significance were evaluated by univariate and multivariate analysis. For DFS and OS, univariate analysis suggested a worse prognostic significance for "peau d'orange" appearance of the skin, clinical evidence of node involvement and poor response to chemotherapy after three cycles, on mammographic criteria. The cumulative dose of doxorubicin after three cycles seemed to have a significant effect on OS (P < 0.03) but was too closely correlated with age to draw definite conclusions. In the multivariate analysis, "peau d'orange", menopausal status and clinical node involvement predicted DFS. "Peau d'orange" and clinical node involvement also predicted OS. Our results indicate that IBC and LABC do not behave differently when treated with our procedure.

Neoadjuvant chemotherapy in 126 operable breast cancers.

126 patients with non-inflammatory operable breast cancer, who otherwise would have undergone modified radical mastectomy (MRM), were treated by induction chemotherapy. Before treatment, every patient had a local and general assessment, and pathological or cytological evidence of malignancy. Patients received, every 3 weeks, the same treatment with doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil (AVCF); methotrexate was added in 80 cases (AVCFM). Tumour shrinkage greater than 50% was documented in 105 (83%) of the 126 women. A higher objective response rate was obtained in aneuploid or high S phase tumours, especially in the patients treated with methotrexate. After chemotherapy, 41 patients were then treated by radiotherapy alone after complete or sub-complete response; 64 had a residual tumour that could be treated by conservative surgery and radiotherapy. Only 19 had MRM and radiotherapy. Histopathological complete remission was documented in 1 case; isolated residual tumour cells were found in 5 patients. Thus primary chemotherapy enhanced the possibility of breast conservation in up to 83% of the cases in a series in which most would have been otherwise subjected to a MRM because of tumour size.

Sequential combination of 5-fluorouracil, cis-platinum and irradiation. 1. Advanced head and neck cancers.

Based on the synergistic action of 5-fluorouracil (5-FUra), cis-dichlorodiamminoplatinum(II) (cis-DDP) and gamma-rays, which was suggested in experiments on murine tumours, a sequential treatment combining irradiation and chemotherapy for human solid tumours known to be resistant to conventional treatments has been developed. A pilot study was carried out on 30 patients with recurring head and neck cancers previously treated by radiotherapy and surgery. The good tolerance and the initial results justified applying this protocol to previously untreated cases. The second study involved 40 patients with stage III and IV tumours. After 3 cycles of combined radio- and chemotherapy followed by a conventional radiotherapy, 78% were good responders (51% in complete remission). Oropharynx and oral cavity, without base of tongue, have a 51% actuarial survival at 3 years when they achieved an early complete remission.

Protection against ischemia: a physiological function of the renin-angiotensin system.

The renin-angiotensin system (RAS) is involved in a complex mechanism that serves to preserve the blood supply to organs so that they can maintain cellular function. Angiotensin II exerts this effect, independently of the blood pressure generated, through two time-related events: a fast opening of the reserve collateral circulation and a much slower response of new vessel formation or angiogenesis. This effect is observed in rats with ligation of the abdominal aorta and in gerbils with abrupt or progressive unilateral carotid artery ligation. Inhibition of the angiotensin-converting enzyme (ACE) or the angiotensin II receptor represses this effect, and it appears that it is mediated through a non-AT1 receptor site of angiotensin II. Many tumors, both benign and malignant, express renin and angiotensin. It seems that the stimulating action of angiotensin II on angiogenesis could also be involved in preserving the blood supply to tumor cells. Administration of converting enzyme inhibitors increases survival and decreases tumor size in tumor-bearing rats. These observations support the hypothesis that the RAS, directly or indirectly, is involved in situations in which the restoration of blood supply is critical for the viability of cells and that it is present not only in normal but also in pathological conditions such as tumors. In view of the ubiquitous presence of renins and angiotensins, it is also likely to be involved in other conditions, such as inflammation, arthritis, diabetic retinopathy, and retrolental fibroplasia, among others in which angiogenesis is prominent. In addition, angiotensin II could be involved, through the counterbalance of the AT1 and AT2 receptors, in the rarefaction of blood vessels as an etiologic component of essential hypertension.

Pancreatitis related to severe acute hypertriglyceridemia during pregnancy: treatment with lipoprotein apheresis.

We report a clinical observation of acute pancreatitis due to severe hypertriglyceridemia in a pregnant woman. In order to decrease the serum triglyceride level rapidly, two lipaphereses were undertaken using the double-filtration technique. This lipoprotein apheresis technique is briefly described and the efficacy in reducing rapidly hypertriglyceridemia is outlined. Like in 3 previously published reports, the patient had a rapid recovery, confirming that lipoprotein apheresis should be an adequate and a well-tolerated treatment in such a condition.

Use of alkaline calcium salts as phosphate binder in uremic patients.

In order to prevent aluminum toxicity induced by the association of aluminum phosphate binder with 1 alpha(OH) vitamin D3 derivatives and the use of deferoxamine with its own hazards to diagnose and treat this toxicity, we have shown in 1982 that it was possible to replace the iatrogenic association of aluminum phosphate binder with 1 alpha OH vitamin D derivatives by oral calcium carbonate taken with the meals in order to bind phosphate and correct the negative calcium balance. This led to the disappearance of the crippling aluminic osteomalacia and adynamic bone diseases in our center. The effectiveness of CaCO3 without 1 alpha(OH)D3 derivatives in the control of hyperparathyroidism in dialysis patients has been proven by the appearance in four patients of our dialysis population of an histological idiopathic adynamic bone disease associated with relative hypoparathyroidism, and by the finding that more than 50% of our dialysis population treated by this sole treatment have plasma concentration of intact PTH below twice the upper limit of normal (that is, the threshold above which only significant histological osteitis fibrosa is observed). Besides the compliance problem, the limit of CaCO3 is the occurrence of hypercalcemia which occurs in about 8% of the measurements. Since calcium acetate binds twice as much phosphate for the same dose of elemental calcium as CaCO3, its use has been recommended. However, clinical experience has shown that in spite of the fact that half the dose of calcium element given as acetate does actually control predialysis plasma phosphate as well as CaCO3, the incidence of hypercalcemia is not decreased, probably because calcium availability at the alkaline pH of the intestine is much greater with Ca acetate. When hypercalcemia is frequent (and not explained by autonomized hyperparathyroidism, adynamic bone disease, overtreatment with vitamin D, granulomatosis or neoplasia) it is necessary either to decrease the dose of calcium and complete the necessary binding of phosphate by adding small doses of Mg(OH)2 or Mg carbonate, provided the dialysate Mg is decreased to 0.2 to 0.35 mmol/liter to prevent hypermagnesemia or to decrease the dialysate calcium (DCa) concentration. The decrease of DCa can be made either just when hypercalcemia occurs or on a systemic basis according to the amount of CaCO3 used and to the necessity of associating 1 alpha(OH) vitamin D3 derivatives.(ABSTRACT TRUNCATED AT 400 WORDS)

The dependency of calcium set point on basal plasma calcium in dialysis patients: a better explanation for the discrepancies regarding its link with PTH secretion than methodological differences.

BACKGROUND: The increase of calcium (Ca) set point in uremic hyperparathyroid patients and its decrease with calcitriol therapy are controversial. Besides methodological differences regarding the experimental protocol for obtaining the sigmoidal curve, mainly differences in definitions of maximal PTH (peak or steady value) and of calcium set point itself have been proposed for the discrepant conclusions. However, two other explanations are possible: the various aluminum load of the patients and the dependency of Ca set point upon the basal plasma ionized calcium (PCa). PATIENTS AND METHODS: Therefore the Ca set point was measured in 2 groups of patients on maintenance dialysis never exposed to aluminum, one of 7 patients with normosecretion of PTH (NPT) and the other of 8 patients with hyperparathyroidism (HPT) before and after 3 intravenous administration of 4 microg of alfacalcidol in a week. The sigmoidal curve was established during a zero Ca dialysis, without Ca replacement for the first 90 minutes and with intravenous infusion of 41 mmoles of Ca during the 150 last minutes. The curvilinear decrease of PCa induced a peak of PTH followed by a decrease while PCa was still decreasing up to the 90th minute. Therefore PTHmax was taken both at the peak and at its lower value observed at the 90th minute (steady PTHmax). Experimental determinations of the Ca set point were made using both definitions of Brown and Felsenfeld and both PTHmax values. In basal conditions, while using any of the values given by the same calculation methodology, Ca set point was not different in NPT and HPT patients. After alfacalcidol, no change in plasma PTH nor in Ca set point was observed in HPT patients. In contrast, in NPT patients alfacalcidol induced a significant decrease of plasma PTH concentrations in association with an increase in basal PCa and in Ca set point, whatever the definitions of the latter and of PTHmax. Calcitriol induced changes in Ca set point and basal PCa were correlated. CONCLUSIONS: 1) In normocalcemic dialysis patients never exposed to aluminium hyperparathyroidism is not explained by an increased Ca set point 2) Calcitriol suppressive effect on PTH secretion is neither explained by a decrease in Ca set point. 3) Ca set point as measured in vivo does not reflect an intrinsic characteristic of the parathyroid glands since it varies with basal PCa. Better than methodological differences, this dependency may explain the discrepant conclusions between the various clinical investigations.

Risk factors of renal failure progression two years prior to dialysis.

AIM: The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intakes, blood lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated. PATIENTS AND METHODS: The link between these parameters and the decrease of creatinine clearance, deltaCcr (according to Cockroft) was assessed in uni- and multivariate analysis in a population of 49 patients (26 women; age 60+/-15 years, weight 79+/-15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for 2 years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at, respectively, 0.82 g/kg/day and 6.5 g/day. RESULTS: The 2-year deltaCcr was 14+/-14 ml/min. It was not different in men and women. This decrease in Ccr was neither significantly different in gomerular disease (17+/-8, n = 14), diabetic nephropathy (12+/-6, n = 7), nephroangiosclerosis (15+/-8, n = 5), interstitial nephritis (12+/-10, n = 14), and PKD (11 +/-12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): deltaCcr = 15+/-14 vs 7+/-7 ml/min (p < 0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of deltaCcr with the initial and 2-year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobine and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the 2-year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and 2-year averaged value), diastolic BP (only for the 2-year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of 2 risk factors of progression (protidemia > or = 66 g/l, DBP > or = 90 mmHg, hemoglobinemia > 11 g/dl, proteinuria > or = 3 g/d, CT > 5 mmol/l) had a significantly greater decrease of Ccr than those with the 3 other combinations at the exception of the association of low protidemia with DBP. CONCLUSION: Diastolic hypertension and low protidemia are the 2 most important factors predicting progression of renal failure. A predictive synergy was furthermore pointed out between low protidemia or diastolic hypertension with proteinuria and cholesterol. On the contrary anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.

Adjuvant chemotherapy with doxorubicin-containing regimen for 326 stage II breast cancers: 15-year results.

Between 1975 and 1986, 326 patients with stage II breast cancer were treated with an adjuvant combination of doxorubicin, vincristine, cyclophosphamide, and 5-fluorouracil (AVCF) following regional therapy (232 modified radical mastectomy, 94 lumpectomies, 304 irradiations). The AVCF regimen consisted of 4-week cycles of doxorubicin (30 mg/m2 day 1, modified radical mastectomy), vincristine (1 mg/m2 day 2), 5-fluorouracil 400 (mg/m2), and cyclophosphamide (300 mg/m2) days 3-6. Two hundred twenty-four patients (pts) had six cycles and 102 pts 12 cycles; 90 pts also received 30 mg daily tamoxifen for 1 year after chemotherapy. As of March 1994, the median follow-up was 130 months (range 86-221). One hundred eighteen pts developed recurrences (7 local, 19 controlateral, 92 metastatic) and 104 died. Estimated disease-free survival (DFS) was 5 years, 76 +/- 5%; 10 years, 64 +/- 5%; 15 years, 54 +/- 9%. Overall survival (OS) was 5 years, 85 +/- 4%; 10 years, 70 +/- 5%; 15 years, 58 +/- 10%. Survival was affected by the number of involved lymph nodes (258 pts were N+), menopausal status (OS at 15 years: 53% for MP+ and 65% for MP-) and Scarff-Bloom-Richardson grading, but not by hormonal receptors, number of courses, or associated hormonotherapy. Minimal cardiac toxicity was induced by doxorubicin either during or subsequent to treatment completion.

Primary chemotherapy in breast cancer: correlation between tumor response and patient outcome.

This study focused on the correlation between tumor response and patient outcome in 329 breast cancers treated with primary chemotherapy. There were 141 stage IIIB tumors, including 109 inflammatory carcinomas. Other malignancies (34 IIIA, 99 IIB, 55 IIA) were operable but considered to be too large (> 3 cm) for conservative surgery and received primary chemotherapy to avoid mastectomy. All received the AVCF regimen, comprising 4-week cycles of doxorubicin (30 mg/m2) day 1, vincristine (1 mg/m2) day 1, 5-fluorouracil (5-FU; 400 mg/m2) days 2 through 5, cyclophosphamide (300 mg/m2) days 2 through 5. In 189 cases, methotrexate (15 mg/m2) was added at day 2 and day 3. Patients received 6 cycles, then underwent locoregional treatment (surgery, radiotherapy, or both) according to tumor regression. The response rate was assessed by clinical, mammographic, and echographic examinations: a 50% rate of objective responses were noted, of which 15% were complete responses (tumor shrinkage allowed breast conservation in 68% of patients who had stages II or IIIA). For the whole population studied, median follow-up was 111 months (range, 60- 196). One hundred fifty-seven patients had disease relapse (48 local, 14 contralateral, 95 distant). Kaplan-Meier estimates showed an increased 10-year overall survival for patients in complete response, as compared with noncomplete response: 70% versus 50% (p < 0.03). Complete response to neoadjuvant chemotherapy seems a good prognostic factor.

Non-AT(1)-receptor-mediated protective effect of angiotensin against acute ischaemic stroke in the gerbil.

Previous studies have shown that angiotensin II (Ang II), by mediating rapid recruitment of collateral circulation, has a protective effect in the setting of acute ischaemia. In an experimental model of acute cerebral ischaemia in the gerbil, Fernandez et al. have reported that the mechanism of the protective effect of Ang 11 is blood pressure (BP)-independent, and that the AT1-receptor antagonist, losartan, but not the ACE inhibitor (ACE-I),enalapril, decreases mortality following unilateral carotid artery ligation. The aim of this study was to examine there producibility of the respective effects of losartan and enalapril, and to verify that these differential effects are drug class-related. Acute cerebral ischaemia was induced in anaesthetised gerbils bv unilateral carotid ligation. The effect of pretreatment with two different ACE-I(enalapril and lisinopril), and two different AT1-receptor antagonists (losartan and candesartan), administered orally or intravenously, on mortality were compared. Kaplan-Meier survival curves at day three were analysed bv a log-rank test. Pretreatment with both enalapril and lisinopril significantly decreased survival at day three compared with controls, while the AT1-receptor antagonists losartan and candesartan, despite similarly lowering BP, did not increase mortality. Coadministration of losartan and enalapril increased mortality to the same extent as enalapril alone. This study confirms that Ang II contributes to protective mechanisms against acute cerebral ischaemia through non AT1-receptor-mediated, BP-independent effects.

[First-line chemotherapy in operable breast neoplasms: results of 3 protocols]. / Chimiothérapie première dans les cancers du sein opérables supérieurs à 3 cm: résultats de 3 protocoles.

In order to avoid modified radical mastectomy, a neoadjuvant approach was adopted in our institute for operable bulky breast cancers. From January, 1982, to December, 1995, 288 patients received primary chemotherapy with 3 different regimens (all doses mg/m2): (1) AVCF/AVCFM, 167 patients (adriamycin 30, vincristine 1 d1, cyclophosphamide 300, fluorouracil 400 d2-d5 and methotrexate 20 d2 and d4, every 28 days); (2) NEM, 78 patients (vinorelbine 25, epirubicin 35, methotrexate 20 d1 and d8, every 28 days); and (3) TNCF, 43 patients (THP-adria 20, d1-d3, vinorelbine 25 d1 and d4, cyclophosphamide 300, fluorouracil 400 d1-d4, every 21 days). Evaluation of the response comprised 3 methods: clinical (C), echographic (E), mammographic (M). The overall objective response rate (C: 63/90/93; E: 49/61/85; M: 53/65/83%) is higher with regimens (2) and (3). The complete response rate was increased 2-fold with TNCF but the hematologic toxicity was very superior with this combination. Patients were all operated for (2) and (3), only several for (1), and the breast conservation rate (68/83/79%) was quite similar in the 3 regimens. The pathological complete response rate reached 23% with TNCF. However the impact on patient survival has to be confirmed.

[Standards, Options and Recommendations for the surgical management of carcinoma of the endometrium]. / Standards, Options et Recommandations pour la prise en charge chirurgicale des patientes atteintes de cancer de l'endomètre.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.