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Integration of social and employment policies has been a highly topical issue over past decades in Europe. Faced with the complex task of facilitating the return to employment of jobless people with multiple barriers to work, several countries have developed integrated structures for delivering labour market and social support.'One stop-shops','integrated jobcenters' and 'interagency collaboration'are some of the tools that are being developed in this context (Askim et al, 2011).

Composição corporal e exigências nutricionais de cálcio e fósforo de cordeiros Santa Inês em crescimento

Dois experimentos foram conduzidos com o objetivo de determinar a composição corporal e estimar as exigências de Ca e P, para ganho em peso, de cordeiros Santa Inês em crescimento. Em cada experimento foram usados 18 animais com 25 a 35 kg de peso vivo (PV), no primeiro, e com 15 a 25 kg no segundo experimento. Seis animais foram abatidos no início de cada experimento para avaliar o conteúdo de Ca e P corporal, servindo como animais referência para o método do abate comparativo, seis animais receberam alimentação ad libitum e seis, alimentação restrita. As exigências líquidas de Ca e P para o ganho em peso foram estimadas a partir da derivação de equações de regressão do logaritmo da quantidade desses minerais presentes no corpo vazio, em função do peso do corpo vazio. As exigências líquidas por quilo de ganho de PV para animais com 15, 25 e 35 kg de PV foram, respectivamente: 11,63, 10,52 e 9,82 g de Ca e 5,82, 4,99 e 4,28 g de P.

The glucose transporter 4 FQQI motif is necessary for Akt Substrate of 160-Kilodalton-dependent plasma membrane translocation but not Golgi-localized g-ear-containing Arf-binding protein-dependent entry into the insulin-responsive storage compartment.

Newly synthesized glucose transporter 4 (GLUT4) enters into the insulin-responsive storage compartment in a process that is Golgi-localized γ-ear-containing Arf-binding protein (GGA) dependent, whereas insulin-stimulated translocation is regulated by Akt substrate of 160 kDa (AS160). In the present study, using a variety of GLUT4/GLUT1 chimeras, we have analyzed the specific motifs of GLUT4 that are important for GGA and AS160 regulation of GLUT4 trafficking. Substitution of the amino terminus and the large intracellular loop of GLUT4 into GLUT1 (chimera 1-441) fully recapitulated the basal state retention, insulin-stimulated translocation, and GGA and AS160 sensitivity of wild-type GLUT4 (GLUT4-WT). GLUT4 point mutation (GLUT4-F5A) resulted in loss of GLUT4 intracellular retention in the basal state when coexpressed with both wild-type GGA and AS160. Nevertheless, similar to GLUT4-WT, the insulin-stimulated plasma membrane localization of GLUT4-F5A was significantly inhibited by coexpression of dominant-interfering GGA. In addition, coexpression with a dominant-interfering AS160 (AS160-4P) abolished insulin-stimulated GLUT4-WT but not GLUT4-F5A translocation. GLUT4 endocytosis and intracellular sequestration also required both the amino terminus and large cytoplasmic loop of GLUT4. Furthermore, both the FQQI and the SLL motifs participate in the initial endocytosis from the plasma membrane; however, once internalized, unlike the FQQI motif, the SLL motif is not responsible for intracellular recycling of GLUT4 back to the specialized compartment. Together, we have demonstrated that the FQQI motif within the amino terminus of GLUT4 is essential for GLUT4 endocytosis and AS160-dependent intracellular retention but not for the GGA-dependent sorting of GLUT4 into the insulin-responsive storage compartment.

Déterminants précoces de la mortalité du patient âgé gravement brûlé

Introduction : Avec le vieillissement de la population, le nombre de patients brûlés âgés a augmenté. La prise en charge médicale et chirurgicale globale des brûlés s'est nettement améliorée mais demeure difficile dans cette population vulnérable. Il manque des facteurs prédictifs précoces pour prédire la mortalité de ces patients. Cette étude a pour objectif d'essayer d'en identifier certains. Méthodes : Etude descriptive rétrospective de données collectées prospectivement dans un système informatisé (MetaVision®) sur une période qui s'étend de janvier 2001 à décembre 2010: 53 variables sont colligées et soumises à des analyses univariées en fonction du devenir chez des patients âgés de plus de 50ans. Résultats : 101 patients sur 363 admissions pendant la même période ont été étudiés : ils sont âgés de 66.6 ± 11.9 ans, brûlés sur 21.5 ± 14.9 % surface corporelle (BSA), et 16 sont décédés (15.8%). Vingt variables sont statistiquement significativement associées avec un décès : BSA, % de brûlure chirurgicale, score de BAUX, BAUX modifié, abbreviated burn severity index (ABSI), SAPS II, insuffisance rénale aiguë et chronique, cardiopathie ischémique, pression intra-abdominale élevée (y.c. syndrome du compartiment abdominal), bilan liquidien cumulé à J5 et à J10, sur-réanimation liquidienne, usage de plasma frais congelé, albuminémie, CRP, bicarbonates, créatinine et nutrition entérale. Conclusion : Plusieurs variables cliniques , certains déjà identifiés, mais également plusieurs nouveaux liés à la réponse physiologique du patient. Une étude ont été identifiées comme étant associés à un pronostic défavorable des patients brûlés âgés incluant un nombre plus élevé de patients permettrait de faire des analyses multivariées et de dégager des facteurs prédictifs combinés.

Efeito de densidade de plantas na produtividade de cultivares de pepino para processamento tipo "cornichon"

O objetivo deste trabalho foi avaliar a produtividade de cultivares de pepino para processamento, tipo "cornichon", semeadas em diferentes espaçamentos. O experimento foi desenvolvido em Petrolina, PE, no período de abril a julho de 1999. Foram estudadas as cultivares para processamento Calypso, Eureka, Prêmio, Vlaspik e Vlasset e os espaçamentos entre plantas de 0,20, 0,30 e 0,50 m, em sistema rasteiro. Os tratamentos foram arranjados no esquema fatorial 5x3, em delineamento de blocos ao acaso, com três repetições. A parcela experimental foi composta de quatro linhas de 3,0 m, com espaços entre elas de 1,0 m, duas plantas por cova, e área útil constituída pelas linhas centrais. O incremento do espaçamento entre plantas teve efeitos lineares negativos na produtividade das cultivares Vlaspik, Vlasset e Prêmio. As menores produtividades das cultivares Calypso e Eureka ocorreram sob espaçamento, respectivamente, de 0,50 e 0,46 m. Os maiores valores de massa de matéria fresca dos frutos foram observados nas cultivares Vlasset (6,94 g/fruto) e Eureka (6,82 g/fruto) que não apresentaram diferenças entre si. Observaram-se efeitos lineares positivos do aumento do espaçamento entre plantas no número de frutos por planta em todas as cultivares. As cultivares apresentaram uma variação de 12,18 a 15,10% de frutos tipo 3 (5,0 a 5,5 cm de comprimento), tendo as cultivares Vlaspik (15,10%), Eureka (14,50%) e Calypso (13,60%) apresentado as maiores proporções, sem diferirem entre si.

Short-term clinical outcomes among patients undergoing transcatheter aortic valve implantation in Switzerland: the Swiss TAVI registry.

AIMS: To evaluate short-term clinical outcomes following transcatheter aortic valve implantation (TAVI) using CE-mark approved devices in Switzerland. METHODS AND RESULTS: The Swiss TAVI registry is a national, prospective, multicentre, monitored cohort study evaluating clinical outcomes in consecutive patients undergoing TAVI at cardiovascular centres in Switzerland. From February 2011 to March 2013, a total of 697 patients underwent TAVI for native aortic valve stenosis (98.1%), degenerative aortic bioprosthesis (1.6%) or severe aortic regurgitation (0.3%). Patients were elderly (82.4±6 years), 52% were females, and the majority highly symptomatic (73.1% NYHA III/IV). Patients with severe aortic stenosis (mean gradient 44.8±17 mmHg, aortic valve area 0.7±0.3 cm²) were either deemed inoperable or at high risk for conventional surgery (STS 8.2%±7). The transfemoral access was the most frequently used (79.1%), followed by transapical (18.1%), direct aortic (1.7%) and subclavian access (1.1%). At 30 days, rates of all-cause mortality, cerebrovascular events and myocardial infarction were 4.8%, 3.3% and 0.4%, respectively. The most frequently observed adverse events were access-related complications (11.8%), permanent pacemaker implantation (20.5%) and bleeding complications (16.6%). The Swiss TAVI registry is registered at ClinicalTrials.gov (NCT01368250). CONCLUSIONS: The Swiss TAVI registry is a national cohort study evaluating consecutive TAVI procedures in Switzerland. This first outcome report provides favourable short-term clinical outcomes in unselected TAVI patients.

G Protein-Coupled Receptor heterodimerization in the brain

G protein-coupled receptors (GPCRs) play critical roles in cellular processes and signaling and have been shown to form heteromers with diverge biochemical and/or pharmacological activities that are different from those of the corresponding monomers or homomers. However, despite extensive experimental results supporting the formation of GPCR heteromers in heterologous systems, the existence of such receptor heterocomplexes in the brain remains largely unknown, mostly because of the lack of appropriate methodology. Herein, we describe the in situ proximity ligation assay procedure underlining its high selectivity and sensitivity to image GPCR heteromers with confocal microscopy in brain sections. We describe here how the assay is performed and discuss advantages and disadvantages of this method compared with other available techniques.

Regulation of frizzled receptor activity at the plasma membrane : an interplay of the receptor, the trimeric G protein Go, and RGS protein and a scaffolding protein Kermit

G-protein-signaling pathways convey extracellular signals inside the cells and regulate distinct physiological responses. This type of signaling pathways consists of three major components: G-protein-coupled receptors (GPCRs), heterotrimeric G proteins (G-proteins) and downstream effectors. Upon ligand binding, GPCRs activate heterotrimeric G proteins to initiate the signaling cascade. Dysfunction of GPCR signaling correlates with numerous diseases such as diabetes, nervous and immune system deficiency, and cancer. As the signaling switcher, G-proteins (Gs, Gq/11, G12/13, and Gi/o) have been an appealing topic of research for decades. A heterotrimeric G-protein is composed of three subunits, the guanine nucleotide associated a-subunit, ß and y subunits. In general, the duration of signaling is determined by the lifetime of activated (GTP bound) Ga subunits. Identification of novel communication partners of Ga subunits appears to be an attractive way to understand the machinery of GPCR signaling. In our lab, we mainly focus on Gao, which is abundantly expressed in the nervous system. Here we present two novel interacting partners of Drosophila Gao: Dhit and Kermit, identified through yeast two-hybrid screening and genetic screening respectively. Dhit is characterized by a small size with a conserved RGS domain and an N-terminal cysteine rich motif. The RGS domain possesses the GAP (GTPase activating protein) activity towards G proteins. However, we found that Dhit exerts not only the GAP activity but also the GDI (guanine nucleotide dissociation inhibitor) activity towards Gao. The unexpected GDI activity is preserved in GAIP/RGS19 - a mammalian homologue of Dhit. Further experiments confirmed the GDI activity of Dhit and GAIP/RGS19 in Drosophila and mammalian cell models. Therefore, we propose that Dhit and its mammalian homologues modulate GPCR signaling by a double suppression of Ga subunits - suppression of their nucleotide exchange with GTP and acceleration of their hydrolysis of GTP. Kermit/GEPC was first identified as a binding partner of GAIP/RGS19 in a yeast two- hybrid screen. Instead of interacting with the Drosophila homologue of GAIP/RGS19 (Dhit), Kermit binds to Gao in vivo and in vitro. The functional consequence of Kermit/Gao interaction is the regulation of localization of Vang (one of the planar cell polarity core components) at the apical membrane. Overall, my work elaborated the action of Gao with its two interaction partners in Gao- mediated signaling pathway. Conceivably, the understanding of GPCR signaling including Gao and its regulators or effectors will ultimately shed light on future pharmaceutical research. - Les voies de signalisation médiées par les protéines G transmettent des signaux extracellulaires à l'intérieur des cellules pour réguler des réponses physiologiques distinctes. Cette voie de signalisation consiste en trois composants majeurs : les récepteurs couplés aux protéines G (GPCRs), les protéines G hétérotrimériques (G-proteins) et les effecteurs en aval. Suite à la liaison du ligand, les GPCRs activent les protéines G hétérotrimériques qui initient la cascade de signalisation. Des dysfonctions dans la signalisation médiée par les GPCRs sont corrélées avec de nombreuses maladies comme le diabète, des déficiences immunes et nerveuses, ainsi que le cancer. Puisque la voie de signalisation s'active et se désactive, les protéines G (Gs, Gq/11, G12/13 et Gi/o) ont été un sujet de recherche attrayant pendant des décennies. Une protéine G hétérotrimérique est composée de trois sous-unités, la sous-unité a associée au nucléotide guanine, ainsi que les sous-unités ß et y. En général, la durée du signal est déterminée par le temps de demi-vie des sous-unités Ga activées (Ga liées au GTP). Identifier de nouveaux partenaires de communication des sous-unités Ga se révèle être un moyen attractif de comprendre la machinerie de la signalisation par les GPCRs. Dans notre laboratoire nous nous sommes concentrés principalement sur Gao qui est exprimée de manière abondante dans le système nerveux. Nous présentons ici deux nouveaux partenaires qui interagissent avec Gao chez la drosophile: Dhit et Kermit, qui ont été identifiés respectivement par la méthode du yeast two-hybrid et par criblage génétique. Dhit est caractérisé par une petite taille, avec un domaine RGS conservé et un motif N- terminal riche en cystéines. Le domaine RGS contient une activité GAP (GTPase activating protein) pour les protéines G. Toutefois, nous avons découvert que Dhit exerce non seulement une activité GAP mais aussi une activité GDI (guanine nucleotide dissociation inhibitor) à l'égard de Gao. Cette activité GDI inattendue est préservée dans RGS19 - un homologue de Dhit chez les mammifères. Des expériences supplémentaires ont confirmé l'activité GDI de Dhit et de RGS19 chez Drosophila melanogaster et les modèles cellulaires mammifères. Par conséquent, nous proposons que Dhit et ses homologues mammifères modulent la signalisation GPCR par une double suppression des sous-unités Ga - suppression de leur nucléotide d'échange avec le GTP et une accélération dans leur hydrolyse du GTP. Kermit/GIPC a été premièrement identifié comme un partenaire de liaison de RGS19 dans le criblage par yeast two-hybrid. Au lieu d'interagir avec l'homologue chez la drosophile de RGS19 (Dhit), Kermit se lie à Gao in vivo et in vitro. La conséquence fonctionnelle de l'interaction Kermit/Gao est la régulation de la localisation de Vang, un des composants essentiel de la polarité planaire cellulaire, à la membrane apicale. Globalement, mon travail a démontré l'action de Gao avec ses deux partenaires d'interaction dans la voie de signalisation médiée par Gao. La compréhension de la signalisation par les GPCRs incluant Gao et ses régulateurs ou effecteurs aboutira à mettre en lumière de futurs axes dans la recherche pharmacologique.

Risk factor profile and management of cerebrovascular patients in the REACH Registry.

BACKGROUND: Cerebrovascular disease (CVD) is a global public health problem. CVD patients are at high risk of recurrent stroke and other atherothrombotic events. Prevalence of risk factors, comorbidities, utilization of secondary prevention therapies and adherence to guidelines all influence the recurrent event rate. We assessed these factors in 18,992 CVD patients within a worldwide registry of stable outpatients. METHODS: The Reduction of Atherothrombosis for Continued Health Registry recruited >68,000 outpatients (44 countries). The subjects were mainly recruited by general practitioners (44%) and internists (29%) if they had symptomatic CVD, coronary artery disease, peripheral arterial disease (PAD) and/or >or=3 atherothrombotic risk factors. RESULTS: The 18,992 CVD patients suffered a stroke (53.7%), transient ischemic attack (TIA) (27.7%) or both (18.5%); 40% had symptomatic atherothrombotic disease in >or=1 additional vascular beds: 36% coronary artery disease; 10% PAD and 6% both. The prevalence of risk factors at baseline was higher in the TIA subgroup than in the stroke group: treated hypertension (83.5/82.0%; p = 0.02), body mass index >or=30 (26.7/20.8%; p < 0.0001), hypercholesterolemia (65.1/52.1%; p < 0.0001), atrial fibrillation (14.7/11.9%; p < 0.0001) and carotid artery disease (42.3/29.7%; p < 0.0001). CVD patients received antiplatelet agents (81.7%), oral anticoagulants (17.3%), lipid-lowering agents (61.2%) and antihypertensives (87.9%), but guideline treatment targets were frequently not achieved (54.5% had elevated blood pressure at baseline, while 4.5% had untreated diabetes). CONCLUSIONS: A high percentage of CVD patients have additional atherothrombotic disease manifestations. The risk profile puts CVD patients, especially the TIA subgroup, at high risk for future atherothrombotic events. Undertreatment is common worldwide and adherence to guidelines needs to be enforced.

Early EEG correlates of neuronal injury after brain anoxia.

OBJECTIVES: EEG and serum neuron-specific enolase (NSE) are used for outcome prognostication in patients with postanoxic coma; however, it is unclear if EEG abnormalities reflect transient neuronal dysfunction or neuronal death. To assess this question, EEG abnormalities were correlated with NSE. Moreover, NSE cutoff values and hypothermic EEG features related with poor outcome were explored.¦METHODS: In a prospective cohort of 61 adults treated with therapeutic hypothermia (TH) after cardiac arrest (CA), multichannel EEG recorded during TH was assessed for background reactivity and continuity, presence of epileptiform transients, and correlated with serum NSE collected at 24-48 hours after CA. Demographic, clinical, and functional outcome data (at 3 months) were collected and integrated in the analyses.¦RESULTS: In-hospital mortality was 41%, and 82% of survivors had good neurologic outcome at 3 months. Serum NSE and EEG findings were strongly correlated (Spearman rho = 0.45; p < 0.001). Median NSE peak values were higher in patients with unreactive EEG background (p < 0.001) and discontinuous patterns (p = 0.001). While all subjects with nonreactive EEG died, 5 survivors (3 with good outcome) had NSE levels >33 μg/L.¦CONCLUSION: The correlation between EEG during TH and serum NSE levels supports the hypothesis that early EEG alterations reflect permanent neuronal damage. Furthermore, this study confirms that absent EEG background reactivity and presence of epileptiform transients are robust predictors of poor outcome after CA, and that survival with good neurologic recovery is possible despite serum NSE levels> 33 μg/L. This underscores the importance of multimodal assessments in this setting.

Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial.

OBJECTIVE: To assess the survival benefit and safety profile of low-dose (850 mg/kg) and high-dose (1350 mg/kg) phospholipid emulsion vs. placebo administered as a continuous 3-day infusion in patients with confirmed or suspected Gram-negative severe sepsis. Preclinical and ex vivo studies show that lipoproteins bind and neutralize endotoxin, and experimental animal studies demonstrate protection from septic death when lipoproteins are administered. Endotoxin neutralization correlates with the amount of phospholipid in the lipoprotein particles. DESIGN: A three-arm, randomized, blinded, placebo-controlled trial. SETTING: Conducted at 235 centers worldwide between September 2004 and April 2006. PATIENTS: A total of 1379 patients participated in the study, 598 patients received low-dose phospholipid emulsion, and 599 patients received placebo. The high-dose phospholipid emulsion arm was stopped, on the recommendation of the Independent Data Monitoring Committee, due to an increase in life-threatening serious adverse events at the fourth interim analysis and included 182 patients. MEASUREMENTS AND MAIN RESULTS: A 28-day all-cause mortality and new-onset organ failure. There was no significant treatment benefit for low- or high-dose phospholipid emulsion vs. placebo for 28-day all-cause mortality, with rates of 25.8% (p = .329), 31.3% (p = .879), and 26.9%, respectively. The rate of new-onset organ failure was not statistically different among groups at 26.3%, 31.3%, 20.4% with low- and high-dose phospholipid emulsion, and placebo, respectively (one-sided p = .992, low vs. placebo; p = .999, high vs. placebo). Of the subjects treated, 45% had microbiologically confirmed Gram-negative infections. Maximal changes in mean hemoglobin levels were reached on day 10 (-1.04 g/dL) and day 5 (-1.36 g/dL) with low- and high-dose phospholipid emulsion, respectively, and on day 14 (-0.82 g/dL) with placebo. CONCLUSIONS: Treatment with phospholipid emulsion did not reduce 28-day all-cause mortality, or reduce the onset of new organ failure in patients with suspected or confirmed Gram-negative severe sepsis.

Subclinical Thyroid Dysfunction and the Risk of Heart Failure in Older Persons at High Cardiovascular Risk.

Context: Subclinical thyroid dysfunction is common in older people. However, its clinical importance is uncertain. Objective: Our objective was to determine the extent to which subclinical hyperthyroidism and hypothyroidism influence the risk of heart failure and cardiovascular diseases in older people. Setting and Design: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) is an prospective cohort study. Patients: Patients included men and women aged 70-82 yr (n = 5316) with known cardiovascular risk factors or previous cardiovascular disease. Main Outcome Measures: Incidence rate of heart failure hospitalization, atrial fibrillation, and cardiovascular events and mortality according to baseline thyroid status were evaluated. Euthyroid participants (TSH =0.45-4.5 mIU/liter) were compared with those with subclinical hyperthyroidism (TSH <0.45 mIU/liter) and those with subclinical hypothyroidism (TSH ≥4.5 mIU/liter, both with normal free T(4)). Results: Subclinical hyperthyroidism was present in 71 participants and subclinical hypothyroidism in 199 participants. Over 3.2 yr follow-up, the rate of heart failure was higher for subclinical hyperthyroidism compared with euthyroidism [age- and sex-adjusted hazard ratio (HR) = 2.93, 95% confidence interval (CI) = 1.37-6.24, P = 0.005; multivariate-adjusted HR = 3.27, 95% CI = 1.52-7.02, P = 0.002). Subclinical hypothyroidism (only at threshold >10 mIU/liter) was associated with heart failure (age- and sex-adjusted HR = 3.01, 95% CI = 1.12-8.11, P = 0.029; multivariate HR = 2.28, 95% CI = 0.84-6.23). There were no strong evidence of an association between subclinical thyroid dysfunction and cardiovascular events or mortality, except in those with TSH below 0.1 or over 10 mIU/liter and not taking pravastatin. Conclusion: Older people at high cardiovascular risk with low or very high TSH along with normal free T(4) appear at increased risk of incident heart failure.

Haemodialysis acutely reduces the plasma levels of ADMA without reversing impaired NO-dependent vasodilation.

End-stage renal disease patients have endothelial dysfunction and high plasma levels of ADMA (asymmetric omega-NG,NG-dimethylarginine), an endogenous inhibitor of NOS (NO synthase). The actual link between these abnormalities is controversial. Therefore, in the present study, we investigated whether HD (haemodialysis) has an acute impact on NO-dependent vasodilation and plasma ADMA in these patients. A total of 24 patients undergoing maintenance HD (HD group) and 24 age- and gender-matched healthy controls (Control group) were enrolled. The increase in forearm SkBF (skin blood flow) caused by local heating to 41 degrees C (SkBF41), known to depend on endothelial NO production, was determined with laser Doppler imaging. SkBF41 was expressed as a percentage of the vasodilatory reserve obtained from the maximal SkBF induced by local heating to 43 degrees C (independent of NO). In HD patients, SkBF41 was assessed on two successive HD sessions, once immediately before and once immediately after HD. Plasma ADMA was assayed simultaneously with MS/MS (tandem MS). In the Control group, SkBF41 was determined twice, on two different days, and plasma ADMA was assayed once. In HD patients, SkBF41 was identical before (82.2+/-13.1%) and after (82.7+/-12.4%) HD, but was lower than in controls (day 1, 89.6+/-6.1; day 2, 89.2+/-6.9%; P<0.01 compared with the HD group). In contrast, plasma ADMA was higher before (0.98+/-0.17 micromol/l) than after (0.58+/-0.10 micromol/l; P<0.01) HD. ADMA levels after HD did not differ from those obtained in controls (0.56+/-0.11 micromol/l). These findings show that HD patients have impaired NO-dependent vasodilation in forearm skin, an abnormality not acutely reversed by HD and not explained by ADMA accumulation.

Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis.

Advanced soft-tissue sarcomas are usually resistant to cytotoxic agents such as doxorubicin and ifosfamide. Antitumor activity has been observed for gemcitabine and docetaxel combination. We conducted a retrospective study on 133 patients (58 males/75 females) with unresectable or metastatic soft-tissue sarcoma. The median age at diagnosis was 51.7 (18-82), with 76 patients with leiomoyosarcoma and 57 patients with other histological subtypes. The initial localizations were limb (44), uterine (32), retroperitoneal (23) and organs or bone (34). Patients received 900 mg/m2 of gemcitabine (days 1 and 8) over 90 min plus 100 mg/m2 of docetaxel (day 8), intravenously every 21 days. Gemcitabine/docetaxel combination was well tolerated with an overall response of 18.4% and with no clear statistical difference between leiomyosarcomas and other histological subtypes (24.2% versus 10.4% (p=0.06)). No difference was found between uterine soft-tissue sarcomas versus others. The median overall survival was 12.1 months (1-28). Better overall survival was correlated with leiomyosarcoma (p=0.01) and with the quality of the response, even for patients with stable disease (p<10(-4)). No statistical difference was found for the initial localization. Response to treatment and overall survival were better for patients in World Health Organization (WHO) performance status classification (PS) 0 at baseline versus patients in WHO PS-1, 2 or 3 (p=0.023 and p<10(-4), respectively). Gemcitabine/docetaxel combination was tolerable and demonstrated better response and survival for leiomyosarcoma, especially for patients in WHO PS-0 at baseline. For the other histological subtypes, the response was not encouraging, but the survival for patients in response or stable suggests further investigation.

Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal.

In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO load (r = 0.82) and between net lipogenesis and the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.