Usability of the SedLine® electroencephalographic monitor of depth of anaesthesia in pigs: a pilot study.

To investigate the usability of the SedLine® monitor in anaesthetized pigs. Five juvenile healthy pigs underwent balanced isoflurane-based general anaesthesia for surgical placement of a subcutaneous jugular venous port. The SedLine® was applied to continuously monitor electroencephalographic (EEG) activity and its modulation during anaesthesia. Computer tomography and magnetic resonance were performed to investigate the relationship between electrodes' positioning and anatomical structures. The pediatric SedLine® EEG-sensor could be easily applied and SedLine®-generated variables collected. An EEG Density Spectral Array (DS) was displayed over the whole procedure. During surgery, the EEG signal was dominated by elevated power in the delta range (0.5-4 Hz), with an underlying broadband signal (where power decreased with increasing frequency). The emergence period was marked by a decrease in delta power, and a more evenly distributed power over the 4-40 Hz frequency range. From incision to end of surgery, mean SedLine®-generated values (± standard deviation) were overall stable [23.0 (± 2.8) Patient State Index (PSI), 1.0% (± 3.8%) Suppression Ratio (SR), 8.8 Hz (± 2.5 Hz) Spectral Edge Frequency 95% (SEF) left, 7.7 Hz (± 2.4 Hz) SEF right], quickly changing during emergence [75.3 (± 11.1) PSI, 0.0 (± 0.0) SR, 12.5 (± 6.6) SEF left 10.4 (± 6.6) SEF right]. Based on the imaging performed, the sensor does not record EEG signals from the same brain areas as in humans. SedLine®-DSA and -generated variables seemed to reflect variations in depth of anaesthesia in pigs. Further studies are needed to investigate this correlation, as well as to define the species-specific brain structures monitored by the EEG-sensor.

Can disbudding of calves (one versus four weeks of age) induce chronic pain?

BACKGROUND: Calf disbudding is a welfare-relevant invasive husbandry procedure. While it is widely recognized that disbudding elicits acute pain, its chronic consequences are currently unknown. OBJECTIVES: Primary aim of this study was to investigate whether disbudding leads to chronic pain in calves; secondary aim was to evaluate the influence of age at disbudding (1 week versus 4 weeks). METHODS: Thirty-four Holstein bull calves, enrolled in a prospective, controlled, randomized trial, underwent either early disbudding (ED) or late disbudding (LD) or sham treatment (control) at 1 and 4 weeks of age. Pain scoring and quantitative sensory tests (von Frey filaments and algometry) were performed at regular intervals up to 105 days of life; neurophysiological determination of nociceptive reflex thresholds and conditioned pain modulation (CPM) up to 90 days. Data was analyzed with the Brunner and Langer model followed by post-hoc test, with level of significance set at 0.05. RESULTS: Thirty-one calves completed the data collection. Signs of chronic sensitization were observed in 38% of disbudded calves (4 in ED and 4 in LD). Pain scores (until 105 days) and allodynia scores (until 60 days) were significantly higher while pressure thresholds (until 105 days) were significantly lower in both groups ED and LD compared to control. Late disbudded calves showed impairment of trigeminal CPM. Lower laser-evoked trigeminal reflex thresholds were found in clinically painful calves compared to control. CONCLUSIONS: The sequelae of disbudding can extend beyond the acute post-procedural phase. Chronic trigeminal sensitization, independently from the age at disbudding can affect individual calves.

Oxidative stress and mitochondrial damage in the pathogenesis of ALS: New perspectives.

This review attempts to reconcile the present dual view of the mechanisms operating in Amyotrophic Lateral Sclerosis (ALS). On one side, oxidative stress, mitochondrial damage and protein aggregation are considered as causative of the disease, as strongly supported by evidence obtained in models based on the expression of ALS-typical mutant SOD1. On the other hand, evidence from models expressing ALS-typical mutations in RNA-binding proteins such as FUS and TDP43 indicate that mRNA (dys)metabolism is a major pathway in this disease. A critical analysis of existing literature suggests that there may be more than one point of intersection.

Structural insights into the multi-determinant aggregation of TDP-43 in motor neuron-like cells.

TDP-43 is aggregated in patients with ALS and FLTD through mechanisms still incompletely understood. Since aggregation in the cytosol is most probably responsible for the delocalization and loss of proper RNA-binding function of TDP-43 in the nucleus, interception of the formation of aggregates may represent a useful therapeutic option. In this study, we investigated the relative importance of the N-terminal and C-terminal moieties of TDP-43 in the aggregation process and the weight of each of the six cysteine residues in determining unfolding and aggregation of the different domains. We report that cytoplasmic inclusions formed by WT and mutant TDP-43 in motor neuron-like NSC34 cells are redox-sensitive only in part, and contain at least two components, i.e. oligomers and large aggregates, that are made of different molecular species. The two N-terminal cysteine residues contribute to the seeding for the first step in oligomerization, which is then accomplished by mechanisms depending on the four cysteines in the RNA-recognition motifs. Cysteine-independent large aggregates contain unfolded isoforms of the protein, held together by unspecific hydrophobic interactions. Interestingly, truncated isoforms are entrapped exclusively in oligomers. Ab initio modeling of TDP-43 structure, molecular dynamics and molecular docking analysis indicate a differential accessibility of cysteine residues that contributes to aggregation propensity. We propose a model of TDP-43 aggregation involving cysteine-dependent and cysteine-independent stages that may constitute a starting point to devise strategies counteracting the formation of inclusions in TDP-43 proteinopathies.

Antihyperlipidemic and antihyperglycemic effects of the Brazilian salsaparrilhas Smilax brasiliensis Spreng. (Smilacaceae) and Herreria salsaparrilha Mart. (Agavaceae) in mice treated with a high-refined-carbohydrate containing diet.

Roots of Smilax species (Smilacaceae), named as salsaparrilha, have been used for centuries in Asia and Americas as depurative (=for "cleaning blood"), diuretic and sudorific. In southeast of Brazil, roots of Herreria salsaparrilha Mart. (Agavaceae) are also named as salsaparrilha and are used for the same purpose. In this study, we have evaluated the antihyperlipidemic and antihyperglycemic effects of extracts from roots of Smilax brasiliensis and H. salsaparrilha in mice fed with high-refined carbohydrate diet (HC). The chemical composition of the products was determined by LC-DAD and LC-MS. Groups of mice that received the HC diet showed an increase in plasma concentrations of glucose, triglycerides and total cholesterol, compared to control group, without treatment (p<0.05). Triglycerides were reduced significantly (p<0.05) in HC diet group that received 100 and 200mg/kg BW/day of both salsaparrilha extracts. Glucose and total cholesterol levels were reduced significantly (p<0.05) in the groups that received the higher doses (200mg/kg BW/day) of both extracts of salsaparrilha. Extracts of S. brasiliensis, at this dose also showed a higher reduction in triglycerides levels (p<0.001) and promoted a significant reduction in the adipocyte area (p<0.05). Both extracts showed the presence of saponins in LC analysis but S. brasiliensis has a higher concentration of phenolics, mainly chlorogenic acid. The presence of steroidal saponins might be responsible for the reduction of the cholesterol levels, while phenolics in S. brasiliensis by the metabolism of triglycerides and better fat distribution. The result is according with the traditional use of these plants and shown their potential for use as functional foods.

Cancer incidence in eighteen cities of the State of São Paulo, Brazil.

OBJECTIVE: As in Brazil cancer registries are mostly based on large cities, there are no estimates per state or per region and information on the disease incidence in the vast in-land areas is very scarce. An incidence survey was conducted in 18 major cities of the state of São Paulo, excluding the capital, aiming to collect information about cancer incidence in the state of São Paulo. METHODS: Of the 18 cities in state of São Paulo included in the survey, all had available resources for cancer management. Data from the year of 1991 were collected by the personnel of the Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Statistics), who were especially trained by the study coordinators at the Fundação Oncocentro de São Paulo (Cancer Center of São Paulo). The collected data were processed and analyzed at the Oncocentro. Data collection, processing, and analyses were performed according to the recommendations of the International Agency for Research on Cancer. RESULTS: Although some discrepancies were observed in cancer incidence rates between the cities, results obtained for all 18 cities combined were remarkably close to those recently found for the city of São Paulo in the year 1993. One remarkable finding was the relatively high cancer incidence rates in both sexes in the city of Santos. CONCLUSIONS: The very similar all-sites cancer incidence rates found in the year 1991, when compared to those for the city of São Paulo in the year 1993, are suggestive that all regions have common cancer-related factors. Nevertheless, other explanations, such as the inclusion in the study of prevalent cases, as well as of non-residents, may have occurred in both studies, biasing the results. There is a need of further studies to confirm the high cancer incidence in Santos.

Inquérito sobre prevalência do tabagismo na classe médica brasileira / Survey on prevalence of smoking among Brazilian physicians

OBJETIVOS. Apresentar os resultados do inquérito sobre a prevalência atual de fumantes entre os médicos do Brasil, segundo suas especialidades, realizado no período de maio a outubro de 1996. MÉTODO. A amostra utilizada foi de respostas espontâneas, constituída por 11.909 médicos associados pagantes da Associaçäo Médica Brasileira, das várias Unidades da Federaçäo e especialidades médicas. RESULTADOS. Constatou-se que 759 (6,4 por cento) säo fumantes regulares e 11.150 (93,6 por cento) säo näo-fumantes; 4.085 médicos (34,3 por cento) säo ex-fumantes. Os maiores índices de näo-fumantes estäo entre os associados de sociedades de especialidades que possuem programas efetivos de controle do tabagismo (pneumologia, cancerologia, cardiologia e otorrinolaringologia). As regiöes geográficas do Norte, Nordeste e Centro-Oeste apresentaram as maiores prevalências de fumantes. O início do fumar está mais presente no grupo de 10-19 anos (72,6 por cento), com distribuiçäo semelhante entre os sexos. Nenhum médico do sexo feminino iniciou o seu vício de fumar antes dos 10 anos de idade. CONCLUSÃO. É de grande importância os médicos receberem informaçöes sobre tabagismo, bem como a realizaçäo de programas de seu controle na sociedades de especialidades e nas federadas da Associçäo Médica Brasileira.

[Survey on prevalence of smoking among Brazilian physicians]. / Inquérito sobre prevalência do tabagismo na classe médica brasileira.

OBJECTIVES: To present the results of the study of the current prevalence of smoking among Brazilian physicians, according to field of specialization. The study was performed in the period from May to October 1996. METHOD: Data were collected by spontaneous reply from 11,909 physicians registered in Brazilian Medical Association, in the various States of Brazil and medical specializations. RESULTS: The results indicated that 759 (6.4%) are regular smokers, 11,150 (93.6%) are non-smokers and that 4,085 (34.3%) are former smokers. The highest rates of non smoking were found among the societies of specialties that have effective smoking control programs (pneumology, oncology, cardiology and otorhinolaryngology). The northern, northeastern and mid-western regions of the country presented the highest prevalences of smoking. The onset of smoking occurs more frequently in the 10-19 years age group (72.6%), with similar distribution in both sexes. There were no female physicians who began smoking before 10 years of age. CONCLUSION: It is very important that physicians receive information regarding smoking as well as to have the development of smoking control programs in the specialty societies and in the regional associations federated to the Brazilian Medical Association.

Evoluçäo histórica do tratamento do câncer de esôfago no Hospital A. C. Camargo / Historical evolution of the treatment of esophageal cancer at the Hospital A. C. Camargo, Säo Paulo, Brazil

OBJETIVOS. De uma casuística de 1.900 pacientes portadores de câncer de esôfago, matriculados no Hospital A.C. Camargo, Sao Paulo, SP, no período de 1947 a 1986, foram estudados 234 casos submetidos a ressecçao cirúrgica. Durante estas quatro décadas aconteceram modificaçoes marcantes na filosofia da terapêutica destas neoplasias. MÉTODO. Foram identificadas cinco diferentes séries históricas e scus resultados apresentados. RESULTADOS. O primeiro grupo (1947-60) consistiu de 47 casos, que somente foram submetidos a cirurgia. 0 segundo grupo (1961-70), com 56 casos, teve radioterapia pré e pós-operatória em baixas doses. A reconstruçao do trânsito foi realizada com cólon subcutâneo. De 1971-75, o mesmo esquema terapêutico foi usado, exceto para a radioterapia pré-operatória, que foi administrada em altas doses (31 casos). No quarto grupo (1976-82), com 68 casos, houve associaçao da quimioterapia à radioterapia. No último grupo (1983-86), com 32 casos, o esquema foi: quimioterapia pré-operatória, ressecçao cirúrgica com reconstruçao pelo estômago, seguida de radioterapia em altas doses no leito cirúrgico e quimioterapia. Os fatores prognósticos estudados que demonstraram significância estatística foram o diâmetro do tumor e o comprometimento linfonodal periesofágico. CONCLUSAO. A sobrevida de cinco anos dos pacientes com este último planejamento terapêutico permitiu uma evoluçao de 3,7 por cento para 9,0 por cento, conseguindo-se, igualmente, sobrevivência de dez anos.

[Historical evolution of the treatment of esophageal cancer at the Hospital A. C. Camargo, São Paulo, Brazil]. / Evolução histórica do tratamento do câncer de esôfago no Hospital A.C. Camargo.

OBJECTIVES: From 1947-1986 we reviewed a historical series of 1,900 cases of esophageal cancers registered at the A.C. Camargo Hospital, São Paulo, Brazil. Two hundred and thirty four cases were submitted to surgical resection. During these 4 decades the treatment philosophy of these tumors has changed. METHOD: Five different historical groups were identified and the results are presented. RESULTS: The first group (1947-60) consisted of 47 cases only submitted to surgical resection. The second group (1961-70) of 56 cases had pre and pos surgery radiotherapy in low doses and the reconstruction was made using subcutaneous colon. From 1971-75 the same approach was used except with high dose preoperative radiotherapy (31 cases). In the 4th group (1976-82) of 68 cases preoperative radiotherapy (high dose) and chemotherapy were used. In the last group (1983-86) composed of 32 cases the treatment was preoperative chemotherapy, surgical resection with gastric reconstruction followed with high doses radiotherapy in the surgical bed and chemotherapy. The only significant prognostic factors in the statistical analysis were tumor size and involvement peri-esophageal lymph nodes. CONCLUSION: A five year survival from 3.7% to 9.0% was obtained through the use of the fifth group treatment planning.

[Risk factors for cancer of the esophagus: a case control study in a metropolitan area of south-eastern Brazil]. / Factores de risco para o câncer de esôfago: estudo caso-controle em área metropolitana da região Sudeste do Brasil.

The association between esophageal cancer and smoking and drinking habits, instruction and nutritional factors was examined by means of the utilization of data of a case-control study which was undertaken in the city of S. Paulo (Brazil). Eighty five cases were compared with two hundred and ninety two hospital controls, with different diseases, including other kinds of cancer. The crude estimations of the odds ratios were calculated for all the variables. Logistic regression was used in the next steps of the analysis. The drinking habit [odds ratio = 3.68, 95% confidence interval (1.74 - 7.78)], the smoking habit [odds ratio 4.86; 95% confidence interval (1.95 - 12.13)] and the frequent eating of hot pepper [odds ratio = 2.48; 95% confidence interval (1.46 - 4.23)] are important risk factors for the disease. The estimate of odds ratio for smoking ordinary cigarette was 3.43 (1.31-8.97) and for smoking of corn straw hand-rolled cigarrette was of 4.18 (1.38-12.66).

Education and mortality from cancer in São Paulo, Brazil.

This study investigated social class differentials in cancer mortality in São Paulo county, Brazil, for the period 1978 to 1982. A measure of socioeconomic status based on education was used, and cancer risk by level of education was estimated by a case-control approach in which other cancers were considered as controls. For most cancers, the socioeconomic differences in risk were similar to those found in western Europe and North America. For lung cancer, however, the highest risk was observed in men and women with the most education. Other cancers related to tobacco--cancer of the larynx, pharynx, and esophagus--showed a negative association with education. The differences between social classes in consumption habits of alcohol and maté and the use of black tobacco are probably responsible for these contrasting patterns. For breast and cervix uteri cancer the social class patterns were similar to those found in developed countries--a positive relationship for breast and a negative one for cervix uteri cancer. The magnitude of the differences observed between social classes for these cancers was frequently greater in South America than in the United States or western Europe.

Cancer risks among European migrants in São Paulo, Brazil.

Using both mortality and incidence data, cancer risk in Italian, Spanish and Portuguese migrants to São Paulo were compared with those in the Brazil-born population, and with those in their countries of origin. Italian and Spanish migrants show changes in cancer risks which are rather similar to those observed in migrants of the same origin in other parts of South America: they increase their rates of oropharyngeal, oesophageal, cervical and breast cancers and they decrease their rates of lung cancers. However, for cancer of the oesophagus, the changes are greater in São Paulo, where migrants acquire rates similar to those of the natives. For colon cancer, rates in Italian migrants decrease in the low risk area of São Paulo and increase in the high risk area of Argentina. Changes in Portuguese migrants are less evident: their rates of colorectal cancer remain high, and, as found for Japanese migrants in São Paulo, they also retain their higher risks of stomach cancer.

Ethnicity and cancer risk in São Paulo, Brazil.

Data from the São Paulo Cancer Registry (Brazil) for the period 1969-1974 are used to investigate ethnic differentials in cancer risk. Risks for specific cancers were estimated for mulattos and blacks relative to whites, using a case-control approach with other cancers as controls. For both sexes, blacks and mulattos are at higher risk than whites for cancer of the esophagus, stomach, and liver and for myeloma; for prostate cancer in males; and for gall bladder, pancreas, and cervix uteri cancers in females. Blacks and mulattos are at lower risk than whites for cancer of the colon, lung, larynx (males only), bladder, bone, testis, breast, and corpus uteri and for melanoma and leukemia. Except for lung and colon cancers, for which life-style habits are the main risk factors, these ethnic differences are similar to those observed in the United States.

Proportional cancer incidence according to selected sites--comparison between residents in the city of S. Paulo, Brazil: Japanese and Brazilian/Portuguese descent.

The percentual distributions of selected sites of cancer cases according to origin, sex and age are compared. Data were obtained from the Registry of Cancer of S. Paulo (School of Public Health of the University of S. Paulo, Brazil). The reference period for inhabitants of Japanese descent was 1969/78 and for those of Brazilian descent, the period was 1969/75. Standardized Proportionate Incidence Ratios (SPIR) with approximate 95% Confidence Intervals (CI) were evaluated using age specific Incidence Ratios of S. Paulo, 1973, as standards. The results agree with findings of previous works on mortality, but show different patterns according to origin. The well known fact that some sub-groups of a population may be different from the overall group is once again brought to the fore. Attention should be drawn to the differences detected for stomach, skin and prostate, in males, and for stomach, skin, cervix and uterus in females.

Cancer incidence rates among Japanese immigrants in the city of São Paulo, Brazil, 1969-78.

Cancer incidence rates among first-generation Japanese immigrants in the city of São Paulo, Brazil, were estimated from the data of the São Paulo Cancer Registry during the years 1969 to 1978. From all registered cases, 2,179 cancer cases of Japan-born residents (1,288 males, 891 females) were selected and age-specific and summary age-adjusted incidence rates (AAIR) were calculated for the selected sites of cancer. The AAIR for all sites except non-melanoma skin cancer was 195.2 per 100,000 population (95 percent confidence interval: 176.4-214.1) in males and 147.3 (134.6-160.0) in females. Stomach cancer had the highest incidence rate of all cancers in both sexes (males, 69.3; females, 32.0). This was followed by cancer of the lung (22.5), esophagus (10.2), colon (8.3), and prostate (7.1) in males; and by breast (24.0), cervix (18.0), colon (8.4), and lung (7.2) in females. When these rates were compared with those among Japanese in Japan, cancer of the stomach and rectum revealed significantly lower rates, while non-melanoma skin cancer, and prostate and breast cancer showed higher rates. No significant increase of colorectal cancer was recognized among Japanese immigrants in São Paulo, contrary to the remarkably high rates of colorectal cancer being observed among Japanese immigrants in the US.

Age at any birth and breast cancer risk.

In an effort to assess the relative importance of age at first birth, age at subsequent births, and total parity to the occurrence of breast cancer, reproductive data from 4,225 women with breast cancer and 12,307 hospitalized women without breast cancer were analyzed by a multiple logistic regression model. Age at first birth was confirmed to be the most important reproductive risk indicator; it was associated with a 3.5% increase of relative risk for every year of increase in age at first birth (the 95% confidence interval of this estimate was 2.3 to 4.7% increase per year). However, age at any birth after the first was also an independent and statistically significant risk indicator; it was associated with a 0.9% increase of relative risk for every year of increase in age at any (and every) birth (the 95% confidence interval of this estimate was 0.4 to 1.5% increase per year). There is evidence that the age of approximately 35 years represents for every birth a critical point; before this age any full-term pregnancy confers some degree of protection; after this age any full-term pregnancy appears to be associated with increase in breast cancer risk. The effect of parity is determined by the age of occurrence of the component pregnancies. While most pregnancies occur under the age of 35, the distribution varies from population to population, and this may account for the differences between populations in whether or not a protective effect is seen for births after the first, and if it is seen, its extent.

Valor da abreugrafia no diagnostico precoce do cancer primitivo de pulmao. / Value of photofluorography in the early diagnosis of primary lung cancer

Os autores analisam 100 casos de cancer primitivo de pulmao, atendidos no periodo de 1957 - 1976, no Departamento de Cirurgia Toracica do Hospital A.C. Camargo da Fundacao Antonio Prudente, cujo primeiro exame realizado foi a abreugrafia. Apenas 6 casos (6,0%) nao apresentavam sintomatologia pulmonar e, desses, 2 casos eram do ECI. Em 28,0% dos casos a abreugrafia nao foi acompanhada de relatorio medico e em 29,2% dos casos o diagnostico foi discordante de cancer de pulmao. A deteccao precoce dessas neoplasias malignas, atraves de exame radiologico dos pulmoes e exame citologico oncotico de escarro a cada 4 meses, deve ser incentivada, apesar da maioria dos estudos nao ter mostrado uma melhoria da sobrevida dos pacientes; o aumento da ressecabilidade do tumor justifica essas medidas, especialmente entre nos cuja inoperabilidade a primeira consulta e ainda elevada, com uma ressecabilidade pequena. Um maior aprimoramento tecnico e controle dos servicos de abreugrafia poderiam ser de grande utilidade para a utilizacao desse exame, associado a citologia oncotica de escarro, num programa de deteccao de cancer de pulmao em grupos de alto risco, pelo seu menor custo