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The results of PRODIGE 7 study demonstrate that the use of HIPEC is not beneficial for patients in the treatment of colorectal carcinomatosis. Nevertheless, a recent study published in NewEnglandJournalofMedicine showed that hyperthermic intraperitoneal chemotherapy (HIPEC) increased overall survival for patients with ovarian peritoneal carcinomatosis. Although, the emergence of targeted therapies (anti-angiogenic agents, PARP-inhibitors, anti-PDL1) results in new standards of treatment in first line or recurrence disease. In this general context, what is the potential interest of HIPEC for the treatment of ovarian carcinoma?, (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Neurolisteriosis is known to affect vulnerable groups, for example neonates or children with immunodeficiency. This is a key point of the current clinical guidelines regarding pediatric meningitis. We report a rare case of neurolisteriosis in an immunocompetent infant, without the typical signs of listeriosis, which led to a delay in administering the appropriate antibiotherapy. This case illustrates the clinical heterogeneity of neurolisteriosis and the relevance of appropriate polymerase chain reaction (PCR) tests when the clinical presentation differs from the current guidelines. This case also reminds us that raw or unpasteurized milk-based food products pose a risk even in immunocompetent infants or children., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: To study prognostic factors of obliteration and risk factors of brain radiation necrosis in order to propose an algorithm for radiosurgery prescription for cerebral arteriovenous malformations (cAVM)., Material and Methods: One hundred and seventy-nine patients were analysed. Radiosurgery delivered 6 or 10 MV X-rays by arc therapy in 84% of cases, or by fixed field in 16% of cases using two different micro-multileaf collimators (micro-MLC). Follow-up consisted of screening radiation necrosis by MRI every 6 months, and assessing local control by arteriography every 2 years. Obliteration was defined as at least 95% reduction of cAVM volume. Cox proportional hazard model was used to evaluate the local control and the appearance of radiation necrosis over time., Results: Local control rate was 82.7% with the mean follow-up of 3.1 years (0.5-11). Significant prognostic factors were: simple nidus (RR=2.8, p<0.0001), number of embolizations before radiosurgery below 4 (RR=2.9, p<0.0001), prescribed dose to the periphery of at least 18 Gy (RR=2, p=0.0002), nidus volume below8cm(3) (RR=1.9, p=0.0002), and number of table positions below six (RR=1.4, p=0.05). Radiation necrosis rate was 11.2% with a mean time to onset of 18 months. Significant predictive factors were: fixed field versus arc therapy (according to MLC RR=9.1, p<0.0001, and RR=15.1, p=0.01), age below 30 years (RR=2.5, p=0.04), depth of cAVM greater than or equal to 7 cm (RR=7.6, p=0.008), and volume of brain tissue covered by the 12 Gy isodose (V12 Gy) of at least 11 cm(3) (RR=7.8, p=0.05)., Conclusion: A radiosurgery prescription algorithm taking into account the prescribed dose to the periphery (> or = 18 Gy) and reduction of V12 Gy was elaborated from these data.

We investigated the inhibition of cell-cycle progression and replication and the induction of the transcriptional response in diploid budding yeast populations exposed to two different doses of gamma-rays resulting in 15 and 85% survival respectively. We studied the kinetics of the cellular response to ionizing treatment during the period required for all of the surviving cells to achieve at least one cell division. The length of these periods increased with the dose. Irradiated populations arrested as large-budded cells containing partially replicated chromosomes. The extent of the S-phase was proportional to the amount of damage and lasted 3 or 7h depending on the irradiation dose. In parallel to the division study, we carried out a kinetic analysis of the expression of 126 selected genes by use of dedicated microarrays. About 26 genes were induced by irradiation and displayed various pattern of expression. Interestingly, 10 repair genes (RAD51, RAD54, CDC8, MSH2, RFA2, RFA3, UBC5, SRS2, SPO12 and TOP1), involved in recombination and DNA synthesis, display similar regulation of expression in the two irradiated populations. Their pattern of expression were confirmed by Northern analysis. At the two doses, the expression of this group of genes closely followed the extended replication period, and their expression resumed when replication restarted. These results suggest that the damage-induced response and DNA synthesis are closely regulated during repair. The analysis of the promoter regions indicates a high occurrence of the three MCB, HAP and UASH regulatory boxes in the promoters of this group of genes. The association of the three boxes could confer an irradiation-replication specific regulation.

Depriving the ovary of exogenous FSH for 1, 2 or 3 d following a bolus injection of FSH was shown to influence the quality of the recovered oocytes. Thus, we compared the developmental competence of oocytes from heifers which had been stimulated for 3 d with FSH (Folltropin-V) and, after an interval of 36, 48 or 60 h, underwent blind transvaginal aspiration. The ovaries of heifers with a palpable or functional corpus luteum were aspirated to remove all large follicles 2 d prior to being injected with either 6 doses of saline (S), 6 doses (20 mg/mL) of FSH (F), or in 6 decreasing doses of FSH (3, 3, 2, 2, 1, 1 mL; Fd). Follicles were counted and classified (medium: 5 to 10 mm, large: >10 mm) with ultrasonography before each aspiration. The oocytes recovered were classified, matured, fertilized, and developed in vitro. On a per animal basis, 1.5, 5.2 and 4.7 large and 1.5, 10.7 and 10.7 medium follicles were counted for S, F and Fd, respectively. A mean of 3.3, 9.1 and 7.7 oocytes was recovered for treatments S, F and Fd, respectively and 58, 94 and 82% were enclosed in a nonexpanded cumulus or a corona layer. Oocyte development rates were based on counts of embryos with 32 or more nuclei at Day 6.5. When oocytes were recovered 36 h after the last injection, an average of 1, 2.7 and 2 embryos per animal was obtained with S, F and Fd, respectively; at 48 h, 0.75, 4.25 and 1 embryo; and at 60 h, 0, 2.5 and 2.7 embryos. Variance analysis was performed, and the protected LSD test indicated that treatment F at 48 h resulted in a significantly higher embryo rate than Fd at 48 h (P<0.05) or S (all times; P<0.05). The reduced effect of the Fd regimen could be due to the decreasing FSH support during follicular growth or to the lower total amount of FSH given. In conclusion, these results indicate an advantage of using moderate (3 d) follicle stimulation followed by a period of FSH starvation to obtain optimal embryo production.

Background: RANTES is a CC-type chemokine protein that acts as a chemoattractant for several kinds of leukocytes, playing an important pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1) into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and inhibits HIV-1 entry into peripheral blood cells. Interaction with chemokine receptors involves a distinct set of residues at the amino terminus of RANTES. This finding was utilized in the development of a chemically modified aminooxypentane derivative of RANTES, AOP-RANTES, that was originally produced from the recombinant protein using semisynthetic methods., Results: AOP-RANTES has been produced by a novel total chemical synthesis that provides efficient, direct access to large amounts of this anti-HIV protein analog. The crystal structure of chemically synthesized AOP-RANTES has been solved and refined at 1.6 A resolution. The protein is a dimer, with the amino-terminal pentane oxime moiety clearly defined., Conclusions: Total chemical synthesis of AOP-RANTES provides a convenient method of producing the multi-milligram quantities of this protein needed to investigate the molecular basis of receptor binding and antiviral activity. This work provides the first truly high-resolution structure of a RANTES protein, although the structure of RANTES was known from previous nuclear magnetic resonance (NMR) determinations.

Ca2+ mobilisation by inositol 1,4,5-trisphosphate (InsP3) is a complex phenomenon which involves positive and negative feedback regulation by cytosolic Ca2+. It has been shown that Ca2+ increased the affinity of [3H]-InsP3 binding to liver membranes and inhibited [3H]-InsP3 binding to cerebellar membranes. We investigated the effects of Ca2+ on the [3H]-InsP3 binding to receptor solubilised and rapidly purified by immunoprecipitation. The InsP3 binding to the purified liver receptor was insensitive to the addition of Ca2+, indicating that Ca2+ did not interact directly with the receptor. The loss of the Ca2+ effect on liver receptor affinity was reproduced by alkaline treatment of liver membranes, which is known to extract the peripheral membrane proteins. This suggests that Ca2+ regulates the liver InsP3 receptor by interacting with a membrane-associated protein. Ca2+ inhibited the binding of [3H]-InsP3 to purified cerebellar receptors as was found with the membrane fraction. The treatment of the purified cerebellar receptor with media of high ionic strength or at alkaline pH did not abolish the effect of Ca2+ on the receptor. This indicates that the inhibitory effect of Ca2+ on [3H]-InsP3 binding to cerebellar membranes occurs either via direct interaction with the receptor or via an integral protein strongly associated with the receptor. In conclusion, the mechanisms of regulation of InsP3-induced Ca2+ release by Ca2+ involve different molecular support in cerebellum and in liver. This may reflect different regulation dependent on the receptor type.

Traditionally the aneurysms of the circle of Willis have been an indication for neurosurgery. New technologies of endovascular treatment with electrically detachable coils resulted in a different therapeutical concept since four years. A series including 140 patients has been treated in our institution from 1 January 1992 to 31 December 1994, 94 of them presenting with a subarachnoid haemorrhage. Out of these 140 patients, 84 were treated with surgery, 51 with the endovascular technique, five with surgery after incomplete or unsuccessful endovascular treatment. Surgery was indicated in patients presenting early after bleeding, devoid of vasospasm, with a favourable Hunt and Hess grading and in aneurysms located in the anterior part of the circle of Willis. Endovascular treatment was indicated in patients admitted with delay, with severe vasospasm, a poor Hunt and Hess grading and in all aneurysms of the vertebrobasilar arterial network. Age was of less importance in comparison to the status of the vessels for selection of the method of treatment. Giant aneurysms are difficult to treat as surgery is faced with the size of the aneurysmal itself and endovascular technique with the width of the aneurysmal neck.

Various therapeutic strategies have been recently proposed to prevent the vasospasm after subarachnoid haemorrhage, and to avoid its clinical consequences. Despite these progresses, mortality and morbidity of delayed ischaemic consequences of vasospasm remain important. Two endovascular treatments have been proposed. The successful use of transluminal angioplasty for vasospasm was first reported by Zubkov in 1984. Transluminal angioplasty is very effective with clinical improvement when the treatment is undertaken without delay after the onset of symptoms. Limitations of this technique are the inaccessibility of distal arteries and the risks (vascular rupture or occlusion). More recently, to overcome these limitations, a selective intraarterial infusion of papaverine has been proposed. These infusions are less risky and can be employed in distal vasospasm. However, clinical results seem to be less favourable and often transient. These two techniques are still used with slightly different indications. According to our experience, it seems reasonable to reserve transluminal angioplasty for symptomatic vasospasm, associated with papaverine or not, and to use papaverine alone in all other cases.

Major improvements have been achieved in endovascular treatment of intracranial aneurysms during the last twenty years. Initial techniques of selective balloon occlusion were progressively replaced by the packing of the aneurysmal pouch with very small and soft metallic devices, named coils, with controlled detachment. In some rare cases, balloon occlusion is still used in order to occlude the parent vessel or to reverse the flow, especially in the vertebro-basilar system. Essential aims for the anaesthesiologist include: complete immobility of the patient throughout the endovascular procedure, systemic anticoagulation in order to avoid any thromboembolic complication during and after treatment, prevention and/or treatment of vasospasm, precise evaluation of fluid balance during the procedure. Our experience is based on 145 aneurysms in 135 patients, treated by endovascular route; 91 (63%) of them were revealed by a subarachnoid haemorrhage (SAH). Their main locations were: the carotid siphon (33.1%), the anterior communicating artery (19.3%), the basilar artery (17.2%) and the middle cerebral artery (17.2%). Thirty-seven of these aneurysms (25.5%) were very small in size with a diameter less than 4 mm. Total or sub-total (more than 90%) occlusion was achieved in 141 aneurysms (90.3%). Thromboembolic complications occurred in eight patients (5.9%), neurological sequelae in one. Other treatment-related complications included the migration of a coil outside the aneurysm in six cases (4.4%) without neurological deficit in one and five ruptures of the aneurysm (3.7%) during the procedure with one lethal issue due to the spontaneous bleeding of a controlateral arterio-venous malformation. Thirteen patients died (9.6%). The cause of the death was related on the initial SAH in 11 of them. The two others were both due to rupture: of a second untreated aneurysm in one case and of an associated arteriovenous malformation in the second one. At present the main indications of endovascular treatment are poor or non indications for neurosurgery. Due to the quality of results, endovascular therapy will be more and more used in case of ruptured or non ruptured aneurysms.

MR Imaging has become the procedure of choice for the exploration of the pituitary region. MR contrast resolution is far better than the finest CT examination, especially concerning the microadenomas and the neurohypophysis. The present paper concerns, at first the major principles of magnetic resonance imaging, its application for the study of the pituitary region including the use of contrast agent (Gadolinium). Lastly, MR anatomy and physiological variations are presented.

The male:female ratio of developing bovine embryos produced and allowed to develop in vitro and in vivo was determined retrospectively from the cytogenetic analysis of 804 embyos. The overall male:female ratio of the 307 (38%) embryos that could be sexed was 162 (52.8%):145 (47.2%) and did not differ (P>0.05) from the expected 1:1 ratio. Among premorula stage embryos produced in vivo (n = 66) and in vitro (n = 30), the ratios were 1.2:1 and 0.76:1, respectively. Among morulae and blastocysts produced in vivo (n = 74), produced and cultured in vitro (n = 106, and produced in vitro and cultured in vivo (n = 31), the ratios were 1.11:1, 1.3:1 and 0.94:1, respectively, none of which differed significantly from 1:1. There was no difference (P>0.05) in the number of cells or mitotic index between male and female morulae and blastocyst, respectively.

Malacoplakia is an uncommon chronic granulomatous inflammation which most frequently involves the urinary bladder of middle-aged women and rarely affects the genital tract. In this paper 10 cases of female genital malacoplakia are reviewed, seven of which have been reported previously in the literature. Genital malacoplakia usually occurs in women 60 years of age or older and most frequently affects the vagina. Vaginal bleeding is a common presenting complaint and the lesion may simulate a malignancy. Four of the 10 patients were receiving corticosteroids at the time of diagnosis. Escherichia coli was cultured from urine or from the lesion itself in half of the cases. The disease appears to be an acquired defect in bactericidal function of histiocytes. Antibiotic therapy and surgical excision are effective, although a recurrence developed in one patient and was successfully re-excised.