18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with known cancer. A cytopathological correlation.

Aim: Pleural effusion is common in cancer patients and to determine its malignant origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic value in staging and follow-up, but its ability to differentiate between malignant and benign effusions is not precisely known. Patients, methods: We examined 50 PET/CT from 47 patients (29 men, 18 women, 60±16 years) with pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3 mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1 oesophageal, 1 melanoma) for FDG uptake in the effusions using SUVmax. This was correlated to cytopathology performed after a median of 21 days (interquartile range -3 to 23), which included pH, relative distribution (macrophages, neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell count. Results: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5 lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman coefficient r = 0.50, p = 0.001), but not with other cytopathological or radiological parameters (ROC area 0.83±0.06). Using a 2.2-mg/l SUV threshold, 12 PET/CT studies were positive and 38 negative with sensitivity, specificity, positive and negative predictive values of 53%, 91%, 75% and 79%, respectively. For NSCLC only (n = 24), ROC area was 0.95±0.04, 7 studies were positive and 17 negative with a sensitivity, specificity, positive and negative predictive values of 83%, 89%, 71 and 94%, respectively. Conclusion: PET/CT may help to differentiate the malignant or benign origin of a pleural effusion with a high specificity in patients with known cancer, in particular NSCLC.

Targeting endoplasmic reticulum signaling pathways in cancer.

The endoplasmic reticulum (ER) orchestrates the production of membrane-bound and secreted proteins. However, its capacity to process the synthesis and folding of protein is limited. Protein overload and the accumulation of misfolded proteins in the ER trigger an adaptive response known as the ER-stress response that is mediated by specific ER-anchored signaling pathways. This response regulates cell functions aimed at restoring cellular homeostasis or at promoting apoptosis of irreparably damaged cells. Activation or deregulation of ER-signaling pathways has been associated with various diseases including cancer. Here we discuss how tumors engage ER-signaling pathways to promote tumorigenesis and how manipulation of this process by anticancer drugs may contribute to cancer treatment.

A new self-expanding aortic stent valve with annular fixation: in vitro haemodynamic assessment.

OBJECTIVE: Balloon-expandable stent valves require flow reduction during implantation (rapid pacing). The present study was designed to compare a self-expanding stent valve with annular fixation versus a balloon-expandable stent valve. METHODS: Implantation of a new self-expanding stent valve with annular fixation (Symetis, Lausanne, Switzerland) was assessed versus balloon-expandable stent valve, in a modified Dynatek Dalta pulse duplicator (sealed port access to the ventricle for transapical route simulation), interfaced with a computer for digital readout, carrying a 25 mm porcine aortic valve. The cardiovascular simulator was programmed to mimic an elderly woman with aortic stenosis: 120/85 mmHg aortic pressure, 60 strokes/min (66.5 ml), 35% systole (2.8 l/min). RESULTS: A total of 450 cardiac cycles was analysed. Stepwise expansion of the self-expanding stent valve with annular fixation (balloon-expandable stent valve) resulted in systolic ventricular increase from 120 to 121 mmHg (126 to 830+/-76 mmHg)*, and left ventricular outflow obstruction with mean transvalvular gradient of 11+/-1.5 mmHg (366+/-202 mmHg)*, systolic aortic pressure dropped distal to the valve from 121 to 64.5+/-2 mmHg (123 to 55+/-30 mmHg) N.S., and output collapsed to 1.9+/-0.06 l/min (0.71+/-0.37 l/min* (before complete obstruction)). No valve migration occurred in either group. (*=p<0.05). CONCLUSIONS: Implantation of this new self-expanding stent valve with annular fixation has little impact on haemodynamics and has the potential for working heart implantation in vivo. Flow reduction (rapid pacing) is not necessary.

Subplate subpopulations in the hypoxic-ischemic neonatal rat brain

Subplate neurons are among the earliest born cells of the neocortex and play a fundamental role in cortical development, in particular in the formation of thalamocortical connections. Subplate abnormalities have been described in several neuropathological disorders including schizophrenia, autism and periventricular eukomalacia (Eastwood and Harrison, Schizophr Res, 79, 2005; McQuillen and Ferriero, Brain Pathol, 15, 2005). We have identified and confirmed a range of specific markers for murine subplate using a microarray based approach and found that different subplate subpopulations are characterized by distinct expression patterns of these genes (Hoerder-Suabedissen et al., Cereb Cortex, 19, 2009). In this current study, we are making use of these markers to investigate neuropathological changes of the subplate after cerebral hypoxia-ischemia (HI) in the neonatal rat. First, we characterized the expression of a number of murine subplate markers in the postnatal rat using immunohistochemistry and in situ hybridization. While several genes (Nurr1, Cplx3, Ctgf and Tmem163) presented very similar expression patterns as in the mouse, others (Ddc, MoxD1 and TRH) were completely absent in the rat cortex. This finding suggests important differences in the subplate populations of these two rodent species. In a neonatal rat model of HI, selective vulnerability of subplate has been suggested using BrdU birthdating methods (McQuillen et al., J Neurosci, 15, 2003). We hypothesized that certain subplate subpopulations could be more susceptible than others and analyzed the above subplate markers in a similar yet slightly milder HI model. Two-day old male rat pups underwent permanent occlusion of the right common carotid artery followed by a period of hypoxia (6% O2, 1.5h or 2h) and were analyzed six days later. Preliminary counts on three subplate subpopulations (Nurr1+, Cplx3+ and Ctgf+ cells, respectively) showed similar reductions in cell numbers for all three groups. In addition, we found that the majority of cases which show changes in the subplate also exhibit lesions in the deep cortical layers VI (identified by FoxP2 expression) and sometimes even layer V (revealed by Er81 immunoreactivity), which questions the selective susceptibility of subplate over other cortical layers under the conditions we used in our model. Supported by MRC, FMO holds a Berrow Scholarship, Lincoln College, Oxford.

Atypical Kawasaki disease with peripheral gangrene and myocardial infarction: therapeutic implications.

We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to gangrene is a rare but serious complication of KD in infants younger than 7 months of age. Treatment has been targeted at reducing arterial inflammation, arteriospasm and thrombosis. We report the first patient with incomplete KD and peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating and antithrombotic agent appeared successful, restoring hand and foot perfusion without significant long-term sequelae. However, PGE1 could have supported development of myocardial infarction by shunting blood away from ischaemic areas distal to a giant coronary artery aneurysm with beginning thrombosis. CONCLUSION. Atypical KD with peripheral gangrene appears to react favourably to treatment with PGE1, but needs careful monitoring to detect early signs of cardiac ischaemia.

Produção de maracujazeiro-amarelo sob diferentes densidades de plantio

O adensamento de plantas em cultivos do maracujazeiro-amarelo é importante por propiciar maior rentabilidade em menor área. O objetivo deste trabalho foi avaliar o efeito de diferentes densidades de plantio na produção, qualidade dos frutos e rentabilidade do maracujazeiro-amarelo. O experimento foi instalado e conduzido em pomar comercial da Fazenda Sant'ana, Município de São Tiago, MG. O delineamento experimental utilizado foi o de blocos casualizados com cinco tratamentos e quatro repetições. Os tratamentos constituíram-se de diferentes espaçamentos na linha de plantio: T1, 1,0 m (3.330 plantas/ha); T2, 1,5 m (2.220 plantas/ha); T3, 2,0 m (1.660 plantas/ha); T4, 3,0 m (1.100 plantas/ha) e T5, 4,0 m (830 plantas/ha). O espaçamento entre linhas foi de 3,0 m em todos os tratamentos. Cada parcela foi constituída de 12 m de comprimento por 3,0 m de largura (36 m²). O plantio foi realizado em outubro de 2001, e a colheita, a partir de abril, estendendo-se até agosto de 2002. A maior produtividade foi estimada em 11,9 t/ha na densidade de 1.841 plantas/ha. O adensamento não altera a qualidade do fruto. A máxima eficiência econômica foi alcançada na densidade de 1.340 plantas/ha, com rentabilidade de R$ 1.321,92/ha.

Peptide-antibody conjugates for tumour therapy: a MHC-class-II-restricted tetanus toxin peptide coupled to an anti-Ig light chain antibody can induce cytotoxic lysis of a human B-cell lymphoma by specific CD4 T cells.

Anti-idiotype antibody therapy of B-cell lymphomas, despite numerous promising experimental and clinical studies, has so far met with limited success. Tailor-made monoclonal anti-idiotype antibodies have been injected into a large series of lymphoma patients, with a few impressive complete tumour remissions but a large majority of negative responses. The results presented here suggest that, by coupling to antilymphoma idiotype antibodies a few molecules of the tetanus toxin universal epitope peptide P2 (830-843), one could markedly increase the efficiency of this therapy. We show that after 2-hr incubation with conjugates consisting of the tetanus toxin peptide P2 coupled by an S-S bridge to monoclonal antibodies directed to the lambda light chain of human immunoglobulin, human B-lymphoma cells can be specifically lysed by a CD4 T-lymphocyte clone specific for the P2 peptide. Antibody without peptide did not induce B-cell killing by the CD4 T-lymphocyte clone. The free cysteine-peptide was also able to induce lysis of the B-lymphoma target by the T-lymphocyte clone, but at a molar concentration 500 to 1000 times higher than that of the coupled peptide. Proliferation assays confirmed that the antibody-peptide conjugate was antigenically active at a much lower concentration than the free peptide. They also showed that antibody-peptide conjugates required an intact processing function of the B cell for peptide presentation, which could be selectively inhibited by leupeptin and chloroquine.(ABSTRACT TRUNCATED AT 250 WORDS)

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia (Spain).

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of 452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Dual-purpose wheat grain and animal production under different grazing periods

The objective of this work was to evaluate the influence of different grazing periods on beef animal production and on wheat forage and grain yield. The experiment was carried out in Pato Branco, PR, Brazil. Six grazing periods were evaluated (0, 21, 42, 63, 84, and 105 days) on dual-purpose wheat cultivar BRS Tarumã. Purunã steers, with average live weight of 162 kg and ten months of age, were kept under continuous grazing using a variable stocking rate, in order to maintain the established sward height of 25 cm. Greater increases in total animal gain (TAG) occurred with longer grazing periods. However, there was little increase after 63 days (490 kg ha-1), and TAG decreased from 552 to 448 kg ha-1 between 84 and 105 days. Grain yield decreased from 2,830 to 610 kg ha-1 when the grazing period increased from 0 to 105 days, but there was little change after 63 days (750 kg ha-1). Cultivar BRS Tarumã shows excellent animal production potential, and the decision on how long wheat pastures should be grazed must be based on relative prices of grain and livestock.

On the convergence of EM-like algorithms for image segmentation using Markov random fields.

Inference of Markov random field images segmentation models is usually performed using iterative methods which adapt the well-known expectation-maximization (EM) algorithm for independent mixture models. However, some of these adaptations are ad hoc and may turn out numerically unstable. In this paper, we review three EM-like variants for Markov random field segmentation and compare their convergence properties both at the theoretical and practical levels. We specifically advocate a numerical scheme involving asynchronous voxel updating, for which general convergence results can be established. Our experiments on brain tissue classification in magnetic resonance images provide evidence that this algorithm may achieve significantly faster convergence than its competitors while yielding at least as good segmentation results.

Unconsciousness and sedation as precipitating factors of diabetic ketoacidosis.

The aim of this study was to identify medico-legal situations characterized by increased vitreous glucose concentrations, potentially lethal blood 3-hydroxybutyrate levels and conditions that could either incapacitate or lead to death on their own. The above was investigated in order to verify whether prolonged states of unconsciousness may play a role in precipitating diabetic ketoacidosis. Six groups of medico-legal situations (corresponding to 206 autopsy cases) were identified. Among these, three cases were characterized by pathologically increased vitreous glucose and blood 3-hydroxybutyrate levels. In one case diabetic ketoacidosis coexisted with underlying features that might have potentially incapacitated or lead to death on their own, whereas in two cases it corresponded with potentially lethal or lethal drug concentrations. The results of this study highlight the usefulness of systematically performing biochemistry in order to identify diabetic ketoacidosis-related deaths, even when autopsy and toxicology results provide apparently conclusive findings.

Adensamento, desbaste e análise econômica na produção do maracujazeiro-amarelo

O objetivo deste trabalho foi avaliar o efeito de diferentes densidades de plantas sobre as características de produção, qualidade de fruto e sobre a rentabilidade econômica do maracujazeiro-amarelo. O experimento foi instalado no município de São Tiago, Minas Gerais. Os tratamentos constituíram-se de diferentes densidades de plantas na linha de plantio: T1=1,0 m (3.330 plantas/ha); T2=2,0 m (1.660 plantas/ha); T3=3,0 m (1.110 plantas/ha); T4= 4,0 m (830 plantas/ha); T5=1,0 m (3.330/1.660 plantas/ha); T6=1,5 m (2.220/1.110 plantas/ha), e T7=2,0 m (1.660/830 plantas/ha). Nos tratamentos T5, T6 e T7, foi feito desbaste de plantas alternadas logo após o término da colheita da primeira safra. A maior produtividade foi estimada em 11,9 t ha-1 na densidade de 1.841 plantas/ha na primeira safra, média de 10,9 t ha-1 na segunda safra e 5,46 t ha-1 na terceira safra. A produtividade total foi menor para o sistema menos adensado (830 plantas/ha), com 25,6 t ha-1 e média de 27,96 t ha-1 para os demais tratamentos. O peso médio de fruto não foi alterado com o adensamento, com exceção da segunda safra, que produziu frutos maiores no plantio adensado. O adensamento não alterou a qualidade do fruto. A média das três safras para as características de qualidade foi: peso médio de fruto (126 g), rendimento de suco (34,9%), sólidos solúveis totais (14,6%) e acidez total titulável (4,9%). A máxima eficiência econômica foi alcançada na densidade de 1.110 plantas/ha.

Aminoethoxivinilglicina no controle do amadurecimento de frutos de caqui cv. Fuyu

Objetivou-se avaliar o efeito de aminoethoxivinilglicina (AVG), aplicado na pós-colheita, no amadurecimento de frutos de caqui (Diospyros kaki L.) cv. Fuyu, armazenados à temperatura de 0 ± 2 ºC. Os frutos foram imersos durante dois minutos em solução de AVG, na concentração de 0; 415; 830 e 1.200 g ha-1 e dissolvidos em água destilada e adição de espalhante adesivo (óleo vegetal) a 0,02% (v/v), secos à temperatura ambiente no barracão e armazenados em câmara fria a 0 ± 2 ºC e 95±2 % UR, e avaliados aos 32 e 52 dias com relação à firmeza, sólidos solúveis, pH da polpa, acidez titulável e injúria por frio. O AVG mostrou-se promissor no uso pós-colheita em caqui, onde os frutos tratados conservaram índices de firmeza linear em função da dose e teores de AT, SS e pH aceitáveis para o 'Fuyu'. Porém os frutos apresentaram translucidez, característica de injúria por frio, indicando a necessidade de novos estudos para se compreender a fisiologia pós-colheita deste fruto.