Somatostatin analogues for the prevention of pancreatic fistula after open pancreatoduodenectomy: A nationwide analysis.

BACKGROUND: Somatostatin analogues (SA) are currently used to prevent postoperative pancreatic fistula (POPF) development. However, its use is controversial. This study investigated the effect of different SA protocols on the incidence of POPF after pancreatoduodenectomy in a nationwide population. METHODS: All patients undergoing elective open pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2014-2017). Patients were divided into six groups: no SA, octreotide, lanreotide, pasireotide, octreotide only in high-risk (HR) patients and lanreotide only in HR patients. Primary endpoint was POPF grade B/C. The updated alternative Fistula Risk Score was used to compare POPF rates across various risk scenarios. RESULTS: 1992 patients were included. Overall POPF rate was 13.1%. Lanreotide (10.0%), octreotide-HR (9.4%) and no protocol (12.7%) POPF rates were lower compared to the other protocols (varying from 15.1 to 19.1%, p = 0.001) in crude analysis. Sub-analysis in patients with HR of POPF showed a significantly lower rate of POPF when treated with lanreotide (10.0%) compared to no protocol, octreotide and pasireotide protocol (21.6-26.9%, p = 0.006). Octreotide-HR and lanreotide-HR protocol POPF rates were comparable to lanreotide protocol, however not significantly different from the other protocols. Multivariable regression analysis demonstrated lanreotide protocol to be positively associated with a low odds-ratio (OR) for POPF (OR 0.387, 95% CI 0.180-0.834, p = 0.015). In-hospital mortality rates were not affected. CONCLUSION: Use of lanreotide in all patients undergoing pancreatoduodenectomy has a potential protective effect on POPF development. Protocols for HR patients only might be favorable too. However, future studies are warranted to confirm these findings.

Hemithyroidectomy versus total thyroidectomy for well differentiated T1-2 N0 thyroid cancer: systematic review and meta-analysis.

BACKGROUND: Evidence for limiting the extent of surgery in patients with low-risk thyroid cancer is lacking. METHODS: A systematic search was performed according to the PRISMA and MOOSE guidelines to assess the effect of total thyroidectomy (TT) with or without radioactive iodine (RAI) treatment versus hemithyroidectomy (HT) on recurrence and overall mortality in patients with differentiated (papillary or follicular) T1-2 N0 thyroid cancer. PubMed, Embase and Cochrane databases were searched, and two authors independently assessed the articles. RESULTS: A total of ten eligible articles were identified. All were observational cohort series, representing a total of 23 134 patients, of which 17 699 were available for meta-analysis. Six studies included patients who had TT followed by RAI treatment. The pooled recurrence rate after TT ± RAI and HT was 2·3 and 2·8 per cent respectively (odds ratio (OR) 1·12, 95 per cent c.i. 0·82 to 1·53; P = 0·48). The pooled 20-year overall survival rate after TT ± RAI was 96·8 per cent, compared with 97·4 per cent for HT (OR 1·30, 0·71 to 2·37; P = 0·40). Overall, higher complication rates were found in the TT ± RAI group. CONCLUSION: Recurrence rates after HT for treatment of well differentiated T1-2 N0 thyroid cancer were similar to those after TT ± RAI, with a lower incidence of treatment-related complications.

ANTECEDENTES: No hay evidencia para limitar la extensión de la cirugía en pacientes con cáncer de tiroides de bajo riesgo. MÉTODOS: Se realizó una búsqueda sistemática siguiendo las recomendaciones PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) y MOOSE (Meta-analysis of Observational Studies in Epidemiology) para evaluar el efecto de la tiroidectomía total (TT) +/− yodo radioactivo (radioactive iodine treatment, RAI) versus hemitiroidectomía (HT) en la recidiva y en la mortalidad global en el cáncer de tiroides diferenciado (papilar/folicular) T1-T2N0. Se realizaron búsquedas en las bases de datos PubMed, Embase y Cochrane, y dos autores evaluaron los artículos de forma independiente. RESULTADOS: Se identificaron un total de 10 artículos de interés. Todos ellos eran estudios de cohortes observacionales, con un total de 23.134 pacientes, de los cuales 17.699 se incluyeron en el metaanálisis. En seis estudios, los pacientes fueron tratados mediante TT seguida de RAI. Las tasas agrupadas de recidiva tras TT +/− RAI y HT fueron 2,3% and 2,8%, respectivamente (razón de oportunidades, odds ratio, OR = 1,12, i.c. del 95% 0,82-1,54, P = 0.48). La supervivencia global a 20 años de TT +/− RAI fue del 96,8% en comparación con el 97,4% para la HT (OR = 1,30, i.c. del 95% 0,71-2,37, P = 0,40). Globalmente, se observaron más complicaciones en el grupo de TT +/− RAI. CONCLUSIÓN: Esta revisión sistemática con metaanálisis demuestra tasas de recidiva similares tras una HT para el tratamiento del cáncer de tiroides T1-2N0 bien diferenciado en comparación con TT +/− RAI, con una menor incidencia de complicaciones relacionadas con el tratamiento.

Unilateral temporary diaphragmatic paralysis secondary to bronchial artery embolization in a girl with cystic fibrosis and massive hemoptysis: a case report.

BACKGROUND: Massive hemoptysis is a serious complication in Cystic Fibrosis (CF), occurring commonly in older patients. Bronchial artery embolization (BAE) can be performed to stop the bleeding. BAE is generally safe and effective, but can sometimes lead to serious complications. We report the first case of temporary unilateral diaphragmatic paralysis associated to lung consolidation following BAE in a pediatric CF female patient. This complication worsened the lung function of the patient who underwent lung transplantation after 9 months. CASE PRESENTATION: A 14 years old female CF patient followed by the CF center of Florence presented low-grade fever, cough increase and recurrent episodes of major hemorrhages such as to carry out a BAE. Within 24 h the patient started to complain of severe thoracic pain in the right hemithorax, increased dyspnea and fever. A computed tomographic angiography and a dynamic fluoroscopic evaluation revealed the right diaphragmatic paralysis, not present before the procedure. After 4 days the clinical condition and radiological imaging had improved with restored mobility of the right hemidiaphragm. Nine months later, she required mechanical ventilation, and subsequently the initiation of extracorporeal membrane oxygenation (ECMO) for a pulmonary exacerbation with septic shock. Lung transplantation in ECMO was performed with success. CONCLUSION: Clinicians should be aware of the possibility of phrenic nerve injury with BAE in pediatric CF patients.

Orexin A in swine corpus luteum.

Orexin A (OXA) is a hypothalamic neuropeptide which acts on 2 known G-protein-coupled receptors. It has been demonstrated that OXA is a central molecular link between food intake and reproduction. More recently, its peripheral role has been investigated, and we demonstrated its involvement in regulating ovarian follicle function. The present study was undertaken to explore a potential physiological role of orexin system in swine corpus luteum, a transient ovarian endocrine organ. Our aim was, first, to analyze the localization and eventual colocalization of OXA and its 2 receptors within the different cell types composing the corpus luteum structure. Second, we wanted to explore the effects of OXA on isolated luteal cells, and finally to verify a potential involvement of OXA in angiogenesis, a crucial event in corpus luteum development. Our data demonstrate the local expression of OXA and its receptors in swine corpus luteum. Luteal cell functions were affected by treatment with OXA. In particular, progesterone production was inhibited (P < 0.05) and nonenzymatic scavenging activity was increased (P < 0.05). Moreover, OXA inhibited (P < 0.05) new vessel growth. Our results suggest that OXA could act locally to play a role in corpus luteum demise.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.

BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.

Orexin system in swine ovarian follicles.

Successful reproduction is strictly linked to metabolic cues. The orexins are a family of hypothalamic neurohormones, well known for their key role in the control of food intake and the involvement in several aspects of the reproductive process. The biological actions of both orexins are carried out through binding to the related Orexin 1 (OX1R) and Orexin 2 (OX2R) G-protein-coupled receptors. The purpose of this study was to investigate the presence of orexin system components in the porcine ovaries, to contribute to expand the knowledge about their pleiotropic role. First, we investigated the localization of orexin A (OXA) and its receptors by immunochemistry in different ovarian districts. Thereafter, we evaluated the expression of the prepro-orexin (PPO) gene and OXA effects on granulosa cell functions. Immunohistochemical study revealed the presence of orexinergic system components in porcine ovarian follicles. Moreover, our data show the expression of PPO messenger RNA in swine ovarian follicles >5 mm. In addition, OXA influences proliferation (P < 0.05), steroidogenic activity (P < 0.05), and redox status of granulosa cells (P < 0.05). Therefore, we hypothesize that OXA could exert a local physiological role in swine ovarian follicles even if further studies are required to deeply define the function of this pleiotropic system.

Effect of the supplementation with a blend containing short and medium chain fatty acid monoglycerides in milk replacer on rumen papillae development in weaning calves.

Feeding of neonates with artificial milk formulas is a popular trend toward early weaning of newborn dairy calves. These milk replacers (MR) should accelerate the rumen development, determining early solid feed intake and leading to better performances in cattle. Previous research demonstrated that sodium butyrate supplementation in MR can affect both small intestine and rumen development. Also acetate and propionate showed similar properties, while only a few studies indicate some potential benefit of monoglycerides on gut functions. The present study is aimed to determine the effect of the supplementation of a blend containing short and medium chain fatty acids monoglycerides (SMCFA) in milk replacer on rumen papillae development and growth performances in weaning calves. Twenty bull calves (about 2 weeks old, weighing around 43kg) were randomly allocated into two groups: control (C) and treated (T). Besides MR and starter diet, the latter offered at libitum, T calves received 0.2% SMCFA in MR. Animals were slaughtered after 56 days from the beginning of the trial. No difference was found between groups either in growth performances or in mean number of papillae/cm(2) of mucosa, total surface of papillae (mm(2))/cm(2) of mucosa or papillary size. In both groups, the morphology of the rumen epithelium was typical of parakeratosis. The cells of the stratum spinosum were directly transformed into swollen, ovoid, still nucleated keratinocytes, particularly at the papillary tip, probably as a result of unphysiological osmolarities caused by high concentrate intake. Degenerated squamous horn cells covered the "balloon like" cells forming several layers, particularly in the places of the rumen mucosa more protected from an abrasive action of solid feed. This was more evident in C animals. The squamous cells covering the papillary tip showed cytoplasmic protrusion, representing remains of the attachment sites of desmosomes, which increased the total absorptive surface and were more numerous and higher in T compared to C animals. It might be hypothesized that SMCFA supplementation in MR could better regulate epithelial cell proliferation and probably have an "emollient effect" leading to an easier "peeling" that might increase efficiency for nutrient transport across the epithelium.

Unmet needs and depression among carers of people newly diagnosed with cancer.

AIMS: The aims of this analysis were to examine levels of unmet needs and depression among carers of people newly diagnosed with cancer and to identify groups who may be at higher risk, by examining relationships with demographic characteristics. METHODS: One hundred and fifty dyads of people newly diagnosed with cancer and their carers, aged 18 years and older, were recruited from four Australian hospitals. People with cancer receiving adjuvant cancer treatment with curative intent, were eligible to participate. Carers completed the Supportive Care Needs Survey-Partners & Caregivers (SCNS-P&C45), and both carers and patients completed the Centre of Epidemiologic-Depression Scale (CES-D). RESULTS: Overall, 57% of carers reported at least one, 37% at least three, 31% at least five, and 15% at least 10 unmet needs; the most commonly endorsed unmet needs were in the domains of information and health care service needs. Thirty percent of carers and 36% of patients were at risk of clinical depression. A weak to moderate positive relationship was observed between unmet needs and carer depression (r=0.30, p<0.001). Carer levels of unmet needs were significantly associated with carer age, hospital type, treatment type, cancer type, living situation, relationship status (in both uni- and multi-factor analysis); person with cancer age and carer level of education (in unifactor analysis only); but not with carer gender or patient gender (in both uni- and multi-factor analyses). CONCLUSION: Findings highlight the importance of developing tailored programmes to systematically assist carers who are supporting patients through the early stages of cancer treatment.

Localization of peripheral autonomic neurons innervating the boar urinary bladder trigone and neurochemical features of the sympathetic component.

The urinary bladder trigone (UBT) is a limited area through which the majority of vessels and nerve fibers penetrate into the urinary bladder and where nerve fibers and intramural neurons are more concentrated. We localized the extramural post-ganglionic autonomic neurons supplying the porcine UBT by means of retrograde tracing (Fast Blue, FB). Moreover, we investigated the phenotype of sympathetic trunk ganglion (STG) and caudal mesenteric ganglion (CMG) neurons positive to FB (FB+) by coupling retrograde tracing and double-labeling immunofluorescence methods. A mean number of 1845.1±259.3 FB+ neurons were localized bilaterally in the L1-S3 STG, which appeared as small pericarya (465.6±82.7 µm2) mainly localized along an edge of the ganglion. A large number (4287.5±1450.6) of small (476.1±103.9 µm2) FB+ neurons were localized mainly along a border of both CMG. The largest number (4793.3±1990.8) of FB+ neurons was observed in the pelvic plexus (PP), where labeled neurons were often clustered within different microganglia and had smaller soma cross-sectional area (374.9±85.4 µm2). STG and CMG FB+ neurons were immunoreactive (IR) for tyrosine hydroxylase (TH) (66±10.1% and 52.7±8.2%, respectively), dopamine beta-hydroxylase (DßH) (62±6.2% and 52±6.2%, respectively), neuropeptide Y (NPY) (59±8.2% and 65.8±7.3%, respectively), calcitonin-gene-related peptide (CGRP) (24.1±3.3% and 22.1±3.3%, respectively), substance P (SP) (21.6±2.4% and 37.7±7.5%, respectively), vasoactive intestinal polypeptide (VIP) (18.9±2.3% and 35.4±4.4%, respectively), neuronal nitric oxide synthase (nNOS) (15.3±2% and 32.9±7.7%, respectively), vesicular acetylcholine transporter (VAChT) (15±2% and 34.7±4.5%, respectively), leu-enkephalin (LENK) (14.3±7.1% and 25.9±8.9%, respectively), and somatostatin (SOM) (12.4±3% and 31.8±7.3%, respectively). UBT-projecting neurons were also surrounded by VAChT-, CGRP-, LENK-, and nNOS-IR fibers. The possible role of these neurons and fibers in the neural pathways of the UBT is discussed.

Neurochemical features of boar lumbosacral dorsal root ganglion neurons and characterization of sensory neurons innervating the urinary bladder trigone.

Porcine lumbosacral dorsal root ganglion (DRG) neurons were neurochemically characterized by using six neuronal markers: calcitonin gene-related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), neurofilament 200kDa (NF200), transient receptor potential vanilloid 1 (TRPV1), and isolectin B4 (IB4) from Griffonia simplicifolia. In addition, the phenotype and cross-sectional area of DRG neurons innervating the urinary bladder trigone (UBT) were evaluated by coupling retrograde tracer technique and immunohistochemistry. Lumbar and sacral DRG neuronal subpopulations were immunoreactive (IR) for CGRP (30 ± 3% and 29 ± 3%, respectively), SP (26 ± 8% and 27 ± 12%, respectively), nNOS (21 ± 4% and 26 ± 7%, respectively), NF200 (75 ± 14% and 81 ± 7%, respectively), and TRPV1 (48 ± 13% and 43 ± 6%, respectively), and labeled for IB4 (56 ± 6% and 43 ± 10%, respectively). UBT sensory neurons, which were distributed from L2 to Ca1 DRG, had a segmental localization, showing their highest density in L4-L5 and S2-S4 DRG. Lumbar and sacral UBT sensory neurons expressed similar percentages of NF200 immunoreactivity (64 ± 33% and 58 ± 12%, respectively) but showed a significantly different immunoreactivity for CGRP, SP, nNOS, and TRPV1 (56 ± 9%, 39 ± 15%, 17 ± 13%, 62 ± 10% vs. 16 ± 6%, 16 ± 11%, 6 ± 1%, 45 ± 24%, respectively). Lumbar and sacral UBT sensory neurons also showed different IB4 labeling (67 ± 19% and 48 ± 16, respectively). Taken together, these data indicate that the lumbar and sacral pathways probably play different roles in sensory transmission from the UBT. The findings related to cell size also reinforced this hypothesis, because lumbar UBT sensory neurons were significantly larger than sacral ones (1,112 ± 624 µm(2) vs. 716 ± 421 µm(2) ).

Experimental study on the location of neurons associated with the first sacral sympathetic trunk ganglion of the pig.

The neurons associated with the left first sacral sympathetic trunk ganglion (STG S1), an autonomic ganglion particularly concerned in the innervation of the smooth and striated musculature associated with pelvic organs, were identified in the pig, using the non-trans-synaptic fluorescent retrograde neuronal tracer Fast Blue. The labelled neurons were located mostly ipsilaterally, in the intermediolateral nucleus of the spinal cord segments T10-L5, in the sympathetic trunk ganglia L3-Co1, in the caudal mesenteric ganglia, in the pelvic ganglia, and in the spinal ganglia T13-S4. Our results could indicate the existence of visceral neuronal circuits concerning the ganglia of the sympathetic trunk and the caudal mesenteric, pelvic and spinal ganglia with or without the intervention of the central nervous system, whose identification and preservation during surgical treatments could be helpful in reducing the risk of subsequent urinary and sexual disfunctions.

A prospective analysis of pain experience, beliefs and attitudes, and pain management of a cohort of Danish surgical patients.

BACKGROUND: Adequacy of pain management is a process indicator of health care quality with consequences for patient outcomes and satisfaction. The reported incidence of moderate to severe postoperative pain worldwide is between 20% and 80%. OBJECTIVES: The purpose was to assess the quality of pain management in a cohort of Danish postoperative patients by examining their pain experience, beliefs about pain and pain treatment, and relationships between pain intensity, its effect on function, and pharmacological pain management. METHODS: The American Pain Society's Patient Outcome Questionnaire was administered to a consecutive cohort of Danish patients who had undergone gastrointestinal, gynaecological, orthopaedic or urological surgery within 24 and 72 h of surgery. RESULTS: Findings indicated uncontrolled pain in 45.5% of patients. These patients reported moderate to severe intensity average pain in the previous 24 h, however, 88.4% of the cohort overall stated they were satisfied or very satisfied with pain treatment. Patients who experienced severe pain only received 50% of available strong opioids, 73.3% of available weak opioids, 100% of available non-steroidal antiinflammatory drugs (NSAIDS) and paracetamol. Further, analgesics prescribed to be administered at fixed intervals were administered 99% of the time; in contrast, all Pro Re Nata (PRN) orders irrespective of analgesic categories, were administered only 25% of the time. CONCLUSIONS: A number of patients experienced significant pain postoperatively. Although multi-modal analgesics were available, analgesic administration practices did not consistently reflect management responsive to patient needs. Despite this, patients were largely satisfied with the care received suggesting the need for further research to understand how patients perceive the efficacy of pain management.

Descriptive analysis of emergency department oxygen use in acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Inconsistencies in oxygen therapy recommendations in acute exacerbation of chronic obstructive pulmonary disease (COPD) may result in variability in emergency department (ED) oxygen management of patients with COPD. The aim of this study was to describe oxygen management in the first 4 h of ED care for patients with exacerbation of COPD. METHODS: A retrospective medical record audit was conducted at four public and one private ED in Melbourne, Australia. Participants were 273 adult ED patients with COPD presenting with a primary complaint of shortness of breath from July 2006 to July 2007. Outcome measures were physiological data, including oxygen saturation (SpO(2)), oxygen delivery devices and flow rates on ED arrival, 1 and 4 h. RESULTS: Oxygen was used in 82.0% of patients. Patients who required oxygen had higher incidence of ambulance transport (P < 0.001), triage category 2 (P = 0.006), home oxygen use (P < 0.001), and increased work of breathing on ED arrival (P < 0.001), and higher median respiratory rate (P < 0.001) and heart rate (P = 0.001). SpO(2) > 90% occurred in the majority of patients (87.5%; 96.4%; 95.6%); however, a considerable number of patients with SpO(2) < 90% were not given oxygen (61.8%; 30%; 45.5%). CONCLUSIONS: A number of patients with documented hypoxaemia were not given oxygen and there may be variables other than oxygen saturation that may influence oxygen use. Future research should focus on increasing the evidence-based supporting oxygen use and better understanding of clinicians' oxygen decision-making in patients with COPD.

Emergency department management of exacerbation of chronic obstructive pulmonary disease: audit of compliance with evidence-based guidelines.

BACKGROUND: Emergency departments (ED) play a key role in management of exacerbation of chronic obstructive airways disease (COPD). Current guidelines for management of exacerbation of COPD showed highest levels of evidence (Level A and B) were related to use of medications and non-invasive positive pressure ventilation (NIPPV). AIMS: The aim of this study was to examine compliance with high level evidence for management of exacerbation of COPD during the first 4 h of ED care. METHODS: A retrospective medical record audit was conducted at four public and one private ED in Melbourne, Australia. Participants were adult patients with COPD presenting to the ED with a primary complaint of shortness of breath from July 2006 to July 2007. Outcome measures were compliance with evidence-based recommendations regarding use of bronchodilators, methylxanthines, steroids and NIPPV. RESULTS: Of 273 patients in this study, 72.4% received short-acting beta-agonist bronchodilators, 37.8% received an inhaled short-acting anticholinergic medication and 56.6% received systemic steroid therapy. NIPPV was used in 21 patients, 15 of whom had documentation of acidosis and/or hypercapnia). CONCLUSIONS: There was variation in the use of high level evidence for the ED management of exacerbation of COPD. The highest rate of compliance was non-use of methylxanthines and the greatest deficit was poor compliance with evidence related to NIPPV. There was also scope for improvement in the use of bronchodilators and systemic steroids.

[Prognostic and predictive factors for gliomas in adults]. / Facteurs pronostiques et prédictifs de réponse des gliomes cérébraux de l'adulte.

Malignant gliomas are the most prevalent type of primary brain tumor in adults. They are classified into astrocytomes, oligodendrogliomes and oligo-astrocytomes on the presumed cell of origin. They are then classified according to their degree of malignancy into low-grade gliomas (I and II) and high-grade gliomas (III an IV) according to WHO classification. Conventional therapy includes surgery, radiotherapy and chemotherapy and is mostly palliative. Because patients with a same histologic diagnosis have variable outcomes, there is a need to develop better prognostic markers to predict tumor behaviour and response to therapy. For patients with low-grade gliomas, several clinical parameters affect prognosis and therapeutic options: histological type, tumor measurements, young age, performance status. Prognostic scores have been established based on a combination of these different clinical factors. For high-grade tumors, prognostic and predictive molecular markers have been identified. The combined loss of 1p and 19q is strongly correlated with the oligodendroglial phenotype and is associated with both chemotherapeutic response and prolonged overall survival in anaplastic (grade III) oligodendrogliomas treated with PCV chemotherapy and probably with temozolomide. Many glioblastomas have dysregulated epidermal growth factor receptor and among them, the co-expression of the mutant receptor subtype EGFRvIII. The clinical significance of these EGFR alterations is still debated. Nevertheless, co-expression of EGFRvIII and PTEN seem to be predictive factor of response to EGFR inhibitors currently tested in glioblastomas. In addition, the MGMT-methylation status is an independent predictor for glioblastoma patients treated with an alkylating agent: the epigenetic inactivation of the DNA repair gene MGMT is associated with a better response to chemotherapy and a better outcome. This status may have important implications for the design of future trials.

[Hypofractionated breast radiotherapy in 13 fractions, perfect tolerance or delayed early reaction? Prospective study of Curie Institute]. / La radiothérapie mammaire hypofractionnée en 13 séances, parfaite tolérance ou réaction cutanée décalée ? Etude prospective de l'institut Curie.

PURPOSE: To assess the skin toxicity of this scheme and the time to its appearance. PATIENTS AND METHODS: Eighty-one prospectively recorded patients (pts), treated in Radiotherapy Department for Breast Cancer (BC) with radiotherapy (RT) to the whole breast at the dose of 42.9Gy per 13 fractions (F) per 5 weeks have been studied. Skin reactions were monitored weekly using the National Cancer Institute-Common Toxicity Criteria scoring system, version 3. All risk factors as tobacco smoking, diabetes, obesity were also recorded. RESULTS: All 81 pts, aged from 40 to 83 years (median: 70 years) received whole breast RT 42.9Gy per 13 F without lymph node irradiation after breast conserving surgery. There were no pts with concurrent chemo- and/or hormonal therapy. Seventeen patients (21%) have been treated using decubitus dorsal (DD) technique and 64 (79%) using the previously described isocentric decubitus lateral (IDL) technique. During the RT, only 34 pts (42%) experienced grade I skin reactions and 47 pts (58%) were without. At the last day of the breast irradiation, there were 66 (81%) grade I (N=59) and II (N=7) skin reactions and 15 pts (19%) without. The early skin tolerance of this scheme was considered to be excellent. But in the 2 weeks after the RT, 20 pts (25%) asked for new clinics with their radiation oncologist as a matter of urgency due to worsening of their skin condition. All of them have been seen by their physician and/or the nurse. Of them, nine presented grade I and 11 presented grade II skin reactions, with necessity of special skin care. The analysis of these results was realized and delayed clinics were organized for all pts treated with this scheme 10-14 days after the end of the radiation treatment. CONCLUSIONS: The breast RT 42.9Gy/13 F have been previously described as an efficacious and well tolerated scheme. This prospective homogeneous group of patients showed that delayed early skin reactions could appear in some cases. Therefore complementary clinics are needed to detect and treat these reactions.

Double labelling immunohistochemical characterization of autonomic sympathetic neurons innervating the sow retractor clitoridis muscle.

Retrograde neuronal tracing and immunohistochemical methods were used to define the neurochemical content of sympathetic neurons projecting to the sow retractor clitoridis muscle (RCM). Differently from the other smooth muscles of genital organs, the RCM is an isolated muscle that is tonically contracted in the rest phase and relaxed in the active phase. This peculiarity makes it an interesting experimental model. The fluorescent tracer fast blue was injected into the RCM of three 50 kg subjects. After a one-week survival period, the ipsilateral paravertebral ganglion S1, that in a preliminary study showed the greatest number of cells projecting to the muscle, was collected from each animal. The co-existence of tyrosine hydroxylase with choline acetyltransferase, neuronal nitric oxide synthase, calcitonin gene-related peptide, leu-enkephalin, neuropeptide Y, substance P and vasoactive intestinal polypeptide was studied under a fluorescent microscope on cryostat sections. Tyrosine hydroxylase was present in about 58% of the neurons projecting to the muscle and was found to be co-localized with each of the other tested substances. Within fast blue-labelled cells negative to the adrenergic marker, small populations of neurons singularly containing each of the other enzymatic markers or peptides were also observed. The present study documents the complexity of the neurochemical interactions that regulate the activity of the smooth myocytes of the RCM and their vascular components.

Rotational spectrum of cyanoacetylene solvated with helium atoms.

The high resolution microwave spectra of He(N)-HCCCN clusters were studied in the size ranges of 1-18 and 25-31. In the absence of an accompanying infrared study, rotational excitation energies were computed by the reptation quantum Monte Carlo method and used to facilitate the search and assignment of R(0) transitions from N > 6, as well as R(1) transitions with N > 1. The assignments in the range of 25-31 are accurate to +/-2 cluster size units, with an essentially certain relative ordering. The rotational transition frequencies decrease with N = 1-6 and then show oscillatory behavior for larger cluster sizes, which is now recognized to be a manifestation of the onset and microscopic evolution of superfluidity. For cluster sizes beyond completion of the first solvation shell the rotational frequencies increase significantly above the large-droplet limit. This behavior, common to other linear molecules whose interaction with He features a strong nearly equatorial minimum, is analyzed using path integral Monte Carlo simulations. The He density in the incipient second solvation shell is shown to open a new channel for long permutation cycles, thus increasing the decoupling of the quantum solvent from the rotation of the dopant molecule.