Fil. tohtori Matti Klinge 24/5 1968

Kirje 24.5.1968

Shorter time to diagnosis and improved stage at presentation in Swiss patients with retinoblastoma treated from 1963 to 2004

Rapport de synthèse : Le rétinoblastome est la tumeur de l'oeil la plus fréquente chez l'enfant. Un diagnostic précoce est important pour sauver le globe oculaire et la survie du patient. Le but de notre étude est de déterminer l'évolution de l'intervalle diagnostique, c'est-à-dire le délai entre les premiers symptômes et la date du diagnostic officiel du rétinoblastome, sur une période de 40 ans en Suisse. Matériel et méthode : Il s'agit d'une étude rétrospective faite sur 139 patients suisses traités pour rétinoblastome durant trois différentes périodes : (1) 1963-1983 ; (2) 1984-1993 ; et (3) 1994-2004. On compare certaines caractéristiques : le sexe du patient, la latéralité de la maladie, les premiers symptômes, leurs observateurs, l'intervalle diagnostique, l'âge au diagnostic, le stade de la maladie, l'histoire familiale. Résultats : 37 patients (26.6%) ont été traités dans la première période ; 44 (31.7%) dans la période 2 et 58 (41.7%) dans la période 3. L'intervalle diagnostique diminue de façon significative de 6.97 mois dans la période 1 à 3.58 dans la période 2 à 2.25 dans la période 3 pour le total des malades. Ceci reste significatif pour les rétinoblastomes unilatéraux. De plus, dans ce même groupe, on observe une diminution significative des stades avancés de la maladie, groupe E selon Murphree (61.5% dans la période 1 ; 46.7% dans la période 2 et 22.2 % dans la période 3). Lorsque la maladie est bilatérale, les mêmes observations se font de façon un peu moins marquée. Il n'y a aucun patient diagnostiqué au stade E de la maladie en présence d'une anamnèse familiale positive. Leucocorie (48.2%) et strabisme (20.1 %) sont les symptômes les plus fréquents durant les 3 périodes. Les seuls facteurs qui influencent significativement le risque d'avoir un stade E de la maladie sont la durée de l'intervalle diagnostic et la période de diagnostic. Conclusion : On constate un progrès dans le diagnostic du rétinoblastome en Suisse, surtout lors de maladie unilatérale. De même, des améliorations sont notées dans la maladie bilatérale mais de façon non significative. Il est donc important de mieux enseigner aux médecins à reconnaître les symptômes oculaires de la maladie et à référer les patients plus tôt aux spécialistes. Abstract : OBECTIVES : Retinoblastoma is the most frequent intraocular malignancy in children. Early diagnosis is essential for globe salvage and patient survival. The aim of our study was to determine how time to diagnosis of retinoblastoma has evolved over a 40-year period in Switzerland. METHOD AND PATIENTS : A retrospective study of 139 Swiss patients with retinoblastoma was performed comparing 3 periods: (1) 1963-1983; (2) 1984-1993; and (3) 1994-2004. Factors taken into account were gender, laterality of retínoblastoma, age at first symptoms, type and first observer of symptoms, time to diagnosis, age at diagnosis, disease stage, and family history. RESULTS : Thirty-seven patients (26.6%) were treated in period 1, 44 (31.7%) in period 2, and S8 (41.7%) in period 3.Overall, the diagnostic interval decreased in a significant way from 6.97 months in period 1 to 3.58 in period 2 and to 2.25 in period 3. When looking separately at unilateral and bilateral disease, the decrease oí the diagnostic interval remained statistically significant in unilateral retinoblastoma; there was also a significant reduction in the number of patients with advanced group E disease (Murphree classification) (61.5% in period 1, 46.7% in period 2, 22.2% in period 3). In bilateral disease, the same observations were made to a lesser extent. However, there were no cases with group E disease in 10 patients with positive family history. Leukornria (48.2%) and strabismus (20.1 %) were the 2 most frequent symptoms throughout the 3 periods. The only factors that statistically influenced the chances of having a diagnosis of group E disease were the diagnostic interval and period of diagnosis. Conclusion : Progress has been made in the diagnosis of retinoblastoma in Switzerland, notably in unilateral disease. Improvement to a lesser extent has also been observed in bilateral cases but without statistical significance. Greater effort is needed to teach physians-in-training to recognize the importance of ocular symptoms and refer patients earlier.

Pseudomonas fluorescens CHA0 produces enantio-pyochelin, the optical antipode of the Pseudomonas aeruginosa siderophore pyochelin.

The siderophore pyochelin is made by a thiotemplate mechanism from salicylate and two molecules of cysteine. In Pseudomonas aeruginosa, the first cysteine residue is converted to its D-isoform during thiazoline ring formation whereas the second cysteine remains in its L-configuration, thus determining the stereochemistry of the two interconvertible pyochelin diastereoisomers as 4'R, 2''R, 4''R (pyochelin I) and 4'R, 2''S, 4''R (pyochelin II). Pseudomonas fluorescens CHA0 was found to make a different stereoisomeric mixture, which promoted growth under iron limitation in strain CHA0 and induced the expression of its biosynthetic genes, but was not recognized as a siderophore and signaling molecule by P. aeruginosa. Reciprocally, pyochelin promoted growth and induced pyochelin gene expression in P. aeruginosa, but was not functional in P. fluorescens. The structure of the CHA0 siderophore was determined by mass spectrometry, thin-layer chromatography, NMR, polarimetry, and chiral HPLC as enantio-pyochelin, the optical antipode of the P. aeruginosa siderophore pyochelin. Enantio-pyochelin was chemically synthesized and confirmed to be active in CHA0. Its potential biosynthetic pathway in CHA0 is discussed.

Agregação de Latossolo Vermelho distrófico típico relacionada com o manejo na região dos cerrados no estado de Minas Gerais

As conseqüências diretas do manejo inadequado do solo são a erosão, a redução da produtividade e a perda de sua sustentabilidade. Os indicadores da qualidade da estrutura do solo são importantes ferramentas para avaliar a sustentabilidade dos sistemas de manejo. Este estudo objetivou avaliar a agregação de um Latossolo Vermelho distrófico típico sob diferentes sistemas de manejo na região dos cerrados em Sete Lagoas (MG). Dentre os sistemas de manejo estudados, a semeadura direta foi o que apresentou a maior percentagem de agregados na classe > 2 mm, menores nas classes < 2 mm e < 1 mm e maior diâmetro médio geométrico dos agregados na camada superficial (0-5 cm). A matéria orgânica apresentou correlação significativa (P < 0,01) e positiva com o índice de floculação (r = 0,89), diâmetro médio geométrico (r = 0,97), classe de agregados > 2 mm (r = 0,92) e correlação negativa com classes de agregados < 2 (r = -0,92) e < 1 mm (r = -0,93). Esses aspectos ressaltam o efeito benéfico da semeadura direta, contribuindo para o manejo sustentado do solo.

Automated analysis of background EEG and reactivity during therapeutic hypothermia in comatose patients after cardiac arrest.

Visual analysis of electroencephalography (EEG) background and reactivity during therapeutic hypothermia provides important outcome information, but is time-consuming and not always consistent between reviewers. Automated EEG analysis may help quantify the brain damage. Forty-six comatose patients in therapeutic hypothermia, after cardiac arrest, were included in the study. EEG background was quantified with burst-suppression ratio (BSR) and approximate entropy, both used to monitor anesthesia. Reactivity was detected through change in the power spectrum of signal before and after stimulation. Automatic results obtained almost perfect agreement (discontinuity) to substantial agreement (background reactivity) with a visual score from EEG-certified neurologists. Burst-suppression ratio was more suited to distinguish continuous EEG background from burst-suppression than approximate entropy in this specific population. Automatic EEG background and reactivity measures were significantly related to good and poor outcome. We conclude that quantitative EEG measurements can provide promising information regarding current state of the patient and clinical outcome, but further work is needed before routine application in a clinical setting.

Daily smoking as a marker of weight control practices among female adolescents

Purpose: There is evidence indicating that adolescent females smoke as a way to control weight. The aim of our research is to assess whether daily smoking is a marker for weight control practices among adolescent females. Methods: Data were drawn from the 2002 Swiss Multicenter Adolescent Survey on Health (SMASH02) data base, a survey including 7,548 [3,838 females] in-school adolescents aged 16-20 years in Switzerland. Among females self-reporting BMI (N _ 3,761), two groups were drawn: daily smokers (DS, N _ 1,273) included all those smoking at least 1 cigarette/day and never smokers (NS, N _ 1,888) included all those having never smoked. Former (N _ 177) and occasional (N _ 423) smokers were not included. Groups were compared on weight control practices (being on a diet, self-induced vomiting, use of doctor-prescribed or over-the-counter appetite suppressors) controlling for possible confounding variables (age, BMI, feeling fat, body image, use of other substances, depression, sport practice, academic track and perceived advanced puberty). Analyses were performed with STATA 9. Bivariate analyses are presented as point-prevalence and multivariate analysis (using logistic regression) are presented as adjusted odds ratio (AOR) and [95% confidence interval]. Results: In the bivariate analysis, DS females were significantly more likely (p _ 0.001) than NS to be on a diet (DS: 33.2%, NS: 22.2%), to self-induce vomiting (DS: 9.0%, NS: 3.3%), and to use doctor prescribed (DS: 2.3%, NS: 0.9%) or over-the-counter (DS: 3.2%, NS: 1.2%) appetite suppressors. In the multivariate analysis, DS females were more likely than NS to be on a diet (AOR: 1.40 [1.17/1.68]), to self-induce vomiting (AOR: 2.07 [1.45/2.97]), and to use doctor-prescribed appetite suppressors (AOR: 1.99 [1.00/ 3.96]). Conclusions: Weight control practices are more frequent among female daily smokers than among never smokers. This finding seems to confirm cigarette smoking as a way to control weight among adolescent females. Health professionals should inquire adolescent female smokers about weight control practices, and this association must be kept in mind when discussing tobacco cessation options with adolescent females. Sources of Support: The SMASH02 survey was funded by the Swiss Federal Office of Public Health and the participating cantons.

Avaliação da disponibilidade de nitrogênio no solo para o trigo em Latossolo Vermelho do Distrito Federal

Em razão da grande importância do nitrogênio na nutrição mineral das plantas, instalou-se um experimento em condições de campo em um Latossolo Vermelho, no ano agrícola 2005, no campo experimental da Embrapa Cerrados, Planaltina (DF), com o objetivo de realizar a calibração de métodos de determinação desse nutriente no solo para a cultura do trigo. Utilizou-se o delineamento experimental de blocos ao acaso com seis repetições, e os tratamentos foram seis doses de N: 0, 70, 140, 210, 280 e 350 kg ha-1. Amostras de solo das camadas de 0-20 e 20-40 cm foram retiradas, e três diferentes extratores químicos foram utilizados para avaliação da disponibilidade de N no solo. Os maiores coeficientes de determinação, obtidos pela regressão quadrática entre a produtividade do trigo e o N do solo extraído pelos diferentes extratores, foram observados nas análises das amostras da camada de 0-20 cm, de acordo com a seguinte ordem: KCl 2 mol L-1 a 100 °C (R2 = 0,997**) > H2O2/MnO2 (R² = 0,992**) > tampão pH 11,2 + NO3- (R² = 0,985**) > tampão pH 11,2 (R² = 0,960**). Os elevados valores dos coeficientes de determinação indicam que a camada de 0-20 cm é a mais recomendada em análises de rotina de N no solo para o trigo. Considerando a simplicidade de análise e o elevado coeficiente de determinação, o método da solução-tampão pH 11,2 + NO3- pode ser indicado para análise de rotina de N no solo. Os níveis críticos econômicos de N no solo calculados pelos diferentes extratores químicos, para as relações preço do quilograma de N/preço do quilograma do trigo de 5 a 7, foram: 90 a 68 mg kg-1 (H2O2/MnO2), 87 a 66 mg kg-1 (KCl 2M a 100 ºC), 81 a 62 mg kg-1 (tampão pH 11,2 + NO3-) e 64 a 47 mg kg-1 (tampão pH 11,2). Já os níveis críticos calculados pelo método matemático de Cate - Nelson foram: 94 mg kg-1 (H2O2/MnO2), 90 mg kg-1 (KCl 2M a 100 ºC), 82 mg kg-1 (tampão pH 11,2 + NO3-) e 61 mg kg-1 (tampão pH 11,2).

Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high altitude dwellers.

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Metais pesados em solos de área de mineração e metalurgia de chumbo: I - Fitoextração

A fitoextração tem sido sugerida como alternativa viável às práticas tradicionais de recuperação de solos contaminados por metais pesados (remoção do solo e destinação em aterros ou coprocessamento em cimento, etc.), em razão dos menores custos e por ser menos impactante ao ambiente. Este trabalho objetivou avaliar a fitoextração induzida (uso de ácido cítrico como agente quelante) de metais pesados, com o cultivo de aveia-preta (Avena strigosa Schreber), girassol (Helianthus annuus L.) e grama-batatais (Paspalum notatum Flügge), em solos poluídos (solos 2, 3 e 4) de uma área de mineração de Pb em Adrianópolis (PR). O solo 1 foi amostrado em área de mata nativa (referência). O experimento foi realizado em casa de vegetação, com três repetições. Foram determinados os teores de Pb, Cd, Cu, Ni, Cr e Zn no solo com HNO3/HCl (3:1) concentrados. Após a colheita das plantas, determinaram-se a massa de matéria seca e os teores de metais pesados nas raízes e parte aérea (digestão nítrico-perclórica). Os solos contaminados (2, 3 e 4) apresentaram as seguintes faixas de teores de metais pesados (mg kg-1): Pb - 2.598,5 a 9.678,2; Cd - 1,9 a 22,2; Cu - 165,5 a 969,2; Ni - 22,6 a 38,4; Cr - 15,2 a 27,8; e Zn - 87,4 a 894,8. A adição de quelante não induziu a uma absorção mais efetiva de metais pesados pelas plantas. O solo 2 possibilitou melhor crescimento das plantas, e o girassol deve ser preferido na fitorremediação das áreas sob as mesmas condições. Na área próxima à planta fabril (solo 3) e nas áreas com grande ocorrência de rejeitos (solo 4), a fitoextração não foi eficiente. Nesses ambientes, recomenda-se o estudo de outras plantas nativas e, ou, exóticas resistentes a altos teores de Pb (solo 3) ou a remobilização de solo mais rejeito para aterros industriais (solo 4).

Identifying the best body mass index metric to assess adiposity change in children.

OBJECTIVE: Although dual-energy X-ray absorptiometry (DEXA) is the preferred method to estimate adiposity, body mass index (BMI) is often used as a proxy. However, the ability of BMI to measure adiposity change among youth is poorly evidenced. This study explored which metrics of BMI change have the highest correlations with different metrics of DEXA change. METHODS: Data were from the Quebec Adipose and Lifestyle Investigation in Youth cohort, a prospective cohort of children (8-10 years at recruitment) from Québec, Canada (n=557). Height and weight were measured by trained nurses at baseline (2008) and follow-up (2010). Metrics of BMI change were raw (ΔBMIkg/m(2) ), adjusted for median BMI (ΔBMIpercentage) and age-sex-adjusted with the Centers for Disease Control and Prevention growth curves expressed as centiles (ΔBMIcentile) or z-scores (ΔBMIz-score). Metrics of DEXA change were raw (total fat mass; ΔFMkg), per cent (ΔFMpercentage), height-adjusted (fat mass index; ΔFMI) and age-sex-adjusted z-scores (ΔFMz-score). Spearman's rank correlations were derived. RESULTS: Correlations ranged from modest (0.60) to strong (0.86). ΔFMkg correlated most highly with ΔBMIkg/m(2) (r = 0.86), ΔFMI with ΔBMIkg/m(2) and ΔBMIpercentage (r = 0.83-0.84), ΔFMz-score with ΔBMIz-score (r = 0.78), and ΔFMpercentage with ΔBMIpercentage (r = 0.68). Correlations with ΔBMIcentile were consistently among the lowest. CONCLUSIONS: In 8-10-year-old children, absolute or per cent change in BMI is a good proxy for change in fat mass or FMI, and BMI z-score change is a good proxy for FM z-score change. However change in BMI centile and change in per cent fat mass perform less well and are not recommended.

Lattice-dynamical study of the premartensitic state of the Cu-Al-Be alloys

Neutron-scattering techniques have been used to study the premartensitic state of a family of Cu-Al-Be alloys, which transform from the bcc phase to an 18R martensitic structure. We find that the phonon modes of the TA2[110] branch have very low energies with anomalous temperature dependence. A slight anomaly at q=2/3 was observed; this anomaly, however, does not change significantly with temperature. No elastic peaks, related to the martensite structure, were found in the premartensitic state of these alloys. The results are compared with measurements, performed under the same instrumental conditions, on two Cu-Al-Ni and a Cu-Zn-Al martensitic alloy.