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OBJECTIVES: To perform an external validation of the diagnostic performance of the three-step strategy proposed by the International Ovarian Tumor Analysis (IOTA) group for classifying adnexal masses as benign or malignant, when ultrasound is performed by non-expert sonographers in the first two steps. The second objective was to assess the diagnostic performance of an alternative strategy using simple-rules risk (SRR), instead of simple rules (SR), in the second step. METHODS: This was a prospective observational study conducted at two university hospitals, from September 2015 to August 2017, of consecutive patients diagnosed with an adnexal mass. All women were evaluated by ultrasound using the IOTA three-step strategy. Non-expert sonographers performed the first step (use of simple descriptors to classify the masses) and the second step (use of SR if the mass could not be classified in the first step); masses that could not be classified in the first two steps were categorized by an expert sonographer based on their subjective assessment (third step). The reference standard was histological diagnosis in patients who underwent surgery or at least 12 months of follow-up in cases managed expectantly. The sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios and overall accuracy of the IOTA three-step strategy were estimated. Furthermore, we evaluated retrospectively an alternative two-step strategy using SRR in the second step to categorize the masses not classifiable with simple descriptors, classifying the lesions as being of low, intermediate or high risk for malignancy. The diagnostic performance of this strategy was estimated by calculating its sensitivity and specificity, assuming surgical intervention for intermediate- or high-risk lesions. RESULTS: The study included 283 patients (median age, 48 (range, 18-90) years), of whom 165 (58.3%) were premenopausal and 118 (41.7%) postmenopausal. Two hundred and sixteen (76.3%) women underwent surgery (154 benign and 62 malignant masses) and 67 (23.7%) were managed expectantly with serial ultrasound follow-up for at least 12 months. All expectantly managed masses were considered benign because no sonographic changes suggestive of malignancy were observed during follow-up. Simple descriptors could be applied in 126 (44.5%) masses. Of the remaining 157 lesions, 112 (39.6%) could be characterized using SR. Therefore, 238 (84.1%) masses could be classified by non-expert sonographers in the first two steps. Of the remaining 45 (15.9%) masses, all could be classified by an expert sonographer. Overall sensitivity, specificity, LR+ and LR- of the IOTA three-step strategy were 95.2%, 97.7%, 42.1 and 0.05, respectively. The diagnostic accuracy was 97.2%. Following the two-step strategy using SRR in the second step, of the 157 lesions not classified with simple descriptors, 42, 38 and 77 presented low, intermediate or high risk for malignancy, respectively. Based on this method, 210 women would have undergone surgical treatment. The sensitivity and specificity of this two-step strategy were 98.4% and 63.8%, respectively. CONCLUSIONS: The IOTA three-step strategy shows high accuracy for discriminating between benign and malignant adnexal lesions when used by non-expert sonographers. An alternative strategy using the SRR calculator in the second step might improve on this diagnostic performance by decreasing the number of surgical interventions and increasing sensitivity. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
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Doenças dos Anexos/diagnóstico , Técnicas de Diagnóstico Obstétrico e Ginecológico/normas , Neoplasias Ovarianas/diagnóstico , Medição de Risco/normas , Ultrassonografia/normas , Doenças dos Anexos/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Funções Verossimilhança , Pessoa de Meia-Idade , Neoplasias Ovarianas/classificação , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco/métodos , Sensibilidade e Especificidade , Ultrassonografia/métodos , Adulto JovemRESUMO
The objective of this study was to examine the effects of a neuromuscular training program combining eccentric hamstring muscle strength, plyometrics, and free/resisted sprinting exercises on knee extensor/flexor muscle strength, sprinting performance, and horizontal mechanical properties of sprint running in football (soccer) players. Sixty footballers were randomly assigned to an experimental group (EG) or a control group (CG). Twenty-seven players completed the EG and 24 players the CG. Both groups performed regular football training while the EG performed also a neuromuscular training during a 7-week period. The EG showed a small increases in concentric quadriceps strength (ES = 0.38/0.58), a moderate to large increase in concentric (ES = 0.70/0.74) and eccentric (ES = 0.66/0.87) hamstring strength, and a small improvement in 5-m sprint performance (ES = 0.32). By contrast, the CG presented lower magnitude changes in quadriceps (ES = 0.04/0.29) and hamstring (ES = 0.27/0.34) concentric muscle strength and no changes in hamstring eccentric muscle strength (ES = -0.02/0.11). Thus, in contrast to the CG (ES = -0.27/0.14), the EG showed an almost certain increase in the hamstring/quadriceps strength functional ratio (ES = 0.32/0.75). Moreover, the CG showed small magnitude impairments in sprinting performance (ES = -0.35/-0.11). Horizontal mechanical properties of sprint running remained typically unchanged in both groups. These results indicate that a neuromuscular training program can induce positive hamstring strength and maintain sprinting performance, which might help in preventing hamstring strains in football players.
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Força Muscular , Condicionamento Físico Humano/métodos , Músculo Quadríceps/fisiologia , Corrida/fisiologia , Futebol/fisiologia , Adolescente , Adulto , Desempenho Atlético/fisiologia , Fenômenos Biomecânicos , Humanos , Masculino , Exercício Pliométrico , Adulto JovemRESUMO
INTRODUCTION: Situs inversus totalis is a rare find and only a small percentage are associated with heart disease; its diagnosis is usually made incidentally. OBJECTIVE: To discuss the diagnostic features of situs inversus totalis and the importance of early diagnosis. CASE REPORTS: Two pediatric patients aged 9 and 14 years who were incidentally diagnosed are reported. The first case presented chest pain and during cardiac auscultation, increased heart sounds were heard on the right precordium and attenuated on the left. An electrocardiogram (ECG) showed P wave and QRS axis equal to +150°, narrow QRS voltage attenuated in V3-V6 precordial leads, and negative T waves in leads V1-V4 and aVL. Chest radiography confirmed dextrocardia, and gastric bubble was on the right and hepatic shadow on the left. Echocardiography showed classic mirror dextrocardia without associated malformations. In the second case, dextrocardia was found incidentally after radiography was requested for the evaluation of scoliosis. ECG showed QRS of +120°, P wave axis of +150° and narrow QRS voltage axis attenuated on left precordial leads. Doppler echocardiography confirmed dextrocardia without associated anomalies. Abdominal ultrasound found the liver in left upper quadrant and the spleen in right upper quadrant. CONCLUSIONS: Early diagnosis of situs inversus totalis is important because the thoracic and abdominal surgical approach is different and certain diseases could be presented with unusual characteristics. Also, after the diagnosis of situs inversus, the presence of associated pathologies such as primary ciliary dyskinesia can be studied (Kartagener syndrome).
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Dextrocardia/diagnóstico , Síndrome de Kartagener/diagnóstico , Situs Inversus/diagnóstico , Adolescente , Dor no Peito/etiologia , Criança , Diagnóstico Precoce , Eletrocardiografia , Humanos , Achados Incidentais , MasculinoRESUMO
The aims of the study were: 1) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the pre-season period; 2) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the in-season period; and 3) to observe if the age and position influenced the variables analyzed. A total of 17 players belonging to the men's ACB league team competing in the Euroleague (age = 23.42 ± 5.28 years-old) participated in the study. The players underwent an anthropometric measurement before and after the pre-season, as well as four evaluations throughout the in-season. Anthropometric indices, somatotype components according to Heath and Carter, and adiposity were calculated. The results show that during the pre-season, body mass, BMI, sum of 6 and 8 skinfolds, waist/hip ratio, adipose tissue (kg), adipose tissue percentage, and endomorphy decreased, while ectomorphy increased. However, no significant changes were found in the variables analyzed throughout the season; except for endomorphy, which increased along the in-season. Playing position and age did not have a significant influence on the changes in the anthropometric variables throughout the pre-season and the in-season. In conclusion, while changes in the anthropometric variables in the pre-season were observed, these remained the same during the in-season.
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Basquetebol , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Somatotipos , Estações do Ano , Estatura , Antropometria , Composição CorporalRESUMO
The effect of layering structures on mechanical and thermal hybrid bacterial cellulose (BC) sheet/Kevlar reinforced epoxy composites was investigated. The BC sheet was extracted from Nata de Coco and used as green reinforcement material hybrid with Kevlar reinforced epoxy composites. The BC/Kevlar reinforced epoxy composite was fabricated by using hand lay-up technique equipped with vacuum bagging system and the BC sheets and Kevlar layers were laminated into different layered structures. The performance of the hybrid BC/Kevlar reinforced epoxy composites was characterized through tensile test and low velocity impact according to ASTM D3039 and ASTM D7136, respectively. The thermal performance of the hybrid composites was characterized by using dynamic mechanical analysis (DMA) test. Tensile test on BC sheet composites with Kevlar and epoxy demonstrated that the addition of BC sheet in BC/Kevlar could not withstand the tensor stress by reducing the tensile stress and Young's modulus. The one layer of Kevlar which was replaced with three to six BC sheets had increased the ability to absorb impact force. The storage modulus (E') and Tan δ were significantly dependent on the number of BC sheets and its layering structure. The highest value of E' was observed when BC sheets were arranged alternately with the Kevlar layers. Different damage mechanisms associated with the number of BC sheets and its layered-structure suggested that the BC sheet was functioning as an impact energy absorber as well as strengthening fibers. This study will upsurge interest in BC reinforced composites and the development of new ideas in automotive, marine and bullet applications.
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BACKGROUND: Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation. OBJECTIVE: To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine. METHODS: Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg(-1), to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric emptying [corrected] by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression. RESULTS: Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30-42) and body mass index was 30 Kg m(-2) (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P = 0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P = 0.004). From the best-fitted regression model (R (2) = 81%, P < 0.0001), a 10% increase in GE at 15 min induced on an average a 135 ± 43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P = 0.03) and insulin (P = 0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P = 0.01). Postprandial increase in CCK (P = 0.002) and PP (P = 0.02) was associated with postprandial symptoms. CONCLUSION: Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management.
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Ingestão de Energia/efeitos dos fármacos , Eritromicina/uso terapêutico , Esvaziamento Gástrico/efeitos dos fármacos , Fármacos Gastrointestinais/uso terapêutico , Obesidade/tratamento farmacológico , Saciação/efeitos dos fármacos , Adulto , Índice de Massa Corporal , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Feminino , Esvaziamento Gástrico/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Sobrepeso/tratamento farmacológico , Sobrepeso/fisiopatologia , Período Pós-Prandial/fisiologia , Saciação/fisiologia , Resultado do Tratamento , Adulto JovemRESUMO
AIM: In this study, we investigated the adequacy of the healthcare response systems to detect and treat faecal incontinence in patients in the primary care areas (PCAs) in a core urban area of Barcelona. METHOD: Patients with a diagnosis of faecal incontinence in the study area were identified from the electronic register of diagnostic codes, and from a manual review of electronic medical records of a random sample of the study population. The remaining variables were obtained through a structured telephone interview. RESULTS: In the study population (n = 65,023) with a previously estimated prevalence of faecal incontinence of 13% [95% confidence interval (CI) 10-17%], 68 cases of faecal incontinence were detected by the health care system (prevalence: 0.10%; 95% CI, 0.08-0.13). Of these, 39 patients (68% women, 68 ± 18 years of age) were interviewed: 18 (46%) reported symptoms lasting for longer than 5-10 years and 20 (51%) had waited for more than 5 years before seeking medical advice. Only 8 (18%) had received any treatment for faecal incontinence, and 18 (46%) reported persistent faecal incontinence at the time of the interview (Vaizey severity score 13 ± 4/24). CONCLUSION: The detection and treatment of faecal incontinence is insufficient in primary care services. Strategies to correct this are needed.
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Incontinência Fecal/terapia , Aceitação pelo Paciente de Cuidados de Saúde , Atenção Primária à Saúde/estatística & dados numéricos , Serviços Urbanos de Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Incontinência Fecal/diagnóstico , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Índice de Gravidade de Doença , Espanha , Fatores de Tempo , Resultado do TratamentoRESUMO
Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirão Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.
Assuntos
Infecções por Vírus de DNA , Torque teno virus , Doadores de Sangue , Transfusão de Sangue , DNA Viral , Genótipo , Humanos , Torque teno virus/genéticaRESUMO
AIMS: To investigate the evolution of the quality of life of patients with chronic obstructive pulmonary disease (COPD) and quantify the impact of exacerbations on the deterioration of quality of life over 2 years. METHODS: Multicentre, observational, prospective 2-year study carried out in primary care. Patients with COPD were seen every 6 months. All the exacerbations developing during the study period were recorded and the quality of life of these patients was measured with the St. George's Respiratory Questionnaire (SGRQ). RESULTS: Twenty-seven physicians participated and collected information on 136 patients with a mean age of 70 years (SD: 9.7) and a mean forced expiratory volume in 1 s (FEV(1)) of 48.7% predicted (SD: 14.5%). The mean global score of the SGRQ was 39.6 at the beginning of the study and 37.9 at the end. Patients without exacerbations improved an average of -5.32 units compared with a worsening of +0.2 among patients with exacerbations (p = 0.023). Among the latter, patients with only one exacerbation improved -3.8 units (p = 0.012) compared with a worsening of +2.4 in those with two or more exacerbations (p = 0.134). The impact of exacerbations was greater in patients with more preserved pulmonary function, with a change in the SGRQ among patients with or without exacerbations of +0.23 and -6.17 (p = 0.017), respectively in patients with a FEV(1) > 50%, vs. +0.18 and -4.39 (p = 0.32) in patients with a FEV(1) = 50%. CONCLUSIONS: Exacerbations are associated with a significant worsening in the quality of life of patients with COPD measured with the SGRQ. The degree of impairment depends on the number of exacerbations, being greater in patients with more preserved pulmonary function.
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Doença Pulmonar Obstrutiva Crônica/psicologia , Qualidade de Vida , Doença Aguda , Idoso , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Capacidade Vital/fisiologiaRESUMO
AIM: To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cataract surgery in Medan, Indonesia. METHODS: In a 3 week period in November 2001, 17 of 43 patients developed signs of endophthalmitis after planned extracapsular cataract surgery. A search for possible causes was undertaken 4 months later. RESULTS: In autoclaved stored distilled water used to dissolve acetylcholine (used in 16 of 17 patients with endophthalmitis) a high amount of endotoxin was detected in a human blood essay, as well as a small number of non-typeable Pseudomonas spp. CONCLUSIONS: These findings suggest that distilled water used as solvent for acetylcholine was responsible for this outbreak of endophthalmitis. As a consequence, we now rely on solvents that are regularly checked for impurities such as an intravenous infusion fluid, rather than on vials with distilled water that is presumed to be sterile and kept for some time.
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Extração de Catarata , Surtos de Doenças , Contaminação de Medicamentos , Endoftalmite/etiologia , Infecções Oculares Bacterianas/etiologia , Microbiologia da Água , Acetilcolina , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/etiologia , Endoftalmite/epidemiologia , Endotoxinas/efeitos adversos , Infecções Oculares Bacterianas/epidemiologia , Humanos , Indonésia/epidemiologia , Complicações Pós-Operatórias , Pseudomonas/isolamento & purificação , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/etiologia , SoluçõesRESUMO
OBJECTIVE: To identify what variables characterizing the patients, exacerbations, and treatment of chronic bronchitis and chronic obstructive pulmonary disease (COPD) are associated with a higher direct health cost. METHOD: Observational pharmacoeconomic study of exacerbations of chronic bronchitis and COPD (of probable bacterial etiology, defined as Anthonisen types I or II). Direct health costs were assessed during 30 days of follow-up. Logistic regression was employed for statistical analysis, with calculation of the adjusted odds ratios (OR). An exacerbation cost greater than 150 euros was defined as the dependent variable. RESULTS: Data on 1164 patients were collected by 252 physicians. Pharmacoeconomic data were complete in 947 patients (82.6%). In the first 30 days, 206 sought medical attention because of unsatisfactory response to treatment (21.8%), 69 (7.3%) attended the emergency room, and 22 (2.3%) were admitted to hospital. Overall, 101 exacerbations (10.7%) were classified as high cost (> 150 euros). Continuous oxygen therapy (OR = 7.58) and previous hospitalization (OR = 2.6) were associated with high-cost exacerbations, whereas diagnosis of chronic bronchitis (OR = 0.41) and treatment of the exacerbation with moxifloxacin or amoxicillin-clavulanic acid as opposed to clarithromycin (OR = 0.38) were associated with low-cost exacerbations. CONCLUSION: Treatment failure was reported for 21.8% of the patients with exacerbations of chronic bronchitis and COPD. Repeated medical visits and requests for complementary tests were the main factors responsible for increased cost. Variables associated with high-cost exacerbations were continuous oxygen therapy, previous hospitalization, and treatment with clarithromycin as opposed to moxifloxacin or amoxicillin-clavulanic acid.
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Bronquite/tratamento farmacológico , Bronquite/economia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/economia , Idoso , Bronquite/complicações , Doença Crônica , Custos e Análise de Custo , Feminino , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de RiscoRESUMO
OBJECTIVES: To determine the level of control in treatment compliance in a sample of patients who were treated with acenocoumarol attended in Primary Care settings. MATERIAL AND METHODS: Cross-sectional study. Patients with non-valvular atrial fibrillation treated with acenocoumarol were included. The sample size was calculated based on previous studies. Data of patients who possessed International Normalized Ratio (INR) values in last 6 months in medical consult were collected. It was considered that the INR control was inadequate when the percentage of INR values within the therapeutic range was less than 60% in the last 6 months. Assessment of compliance by telephone interview was conducted by the Morisky-Green Test. RESULTS: One hundred and ninety-one patients, 110 women (57.6%) with an average age of 76.5±9.4 years were included. Seventy-six patients (39.8%) were in therapeutic range (INR: 2-3) and 115 patients (60.2%) were out of range (below 2 the 20.9% and above 3 the 39.3%). Poor control of INR increased to the age of 85 years (<75 years: 57.8%; 75-85 years: 67.6%;>85 years: 61.5%). Ninety patients responded to the compliance questionnaire (78.3%), being compliant 74 (82.2%) and non-compliant 16 (17.8%). CONCLUSIONS: Six of 10 patients undergoing treatment with acenocoumarol are out of range and nearly 2 of each 10 patients out of range does not accomplish the treatment. We call attention to the need to make a systematically review of adherence in anticoagulated patients attended in Primary Care settings.
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Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Coeficiente Internacional Normatizado , Adesão à Medicação/estatística & dados numéricos , Atenção Primária à Saúde , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirão Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.
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In maize the transposable elements Activator/Dissociation (Ac/Ds) transpose shortly after replication from one of the two resulting chromatids ("chromatid selectivity"). A model has been suggested that explains this phenomenon as a consequence of different affinity for Ac transposase binding to holo-, hemi-, and unmethylated transposon ends. Here we demonstrate that in petunia cells a holomethylated Ds is unable to excise from a nonreplicating vector and that replication restores excision. A Ds element hemi-methylated on one DNA strand transposes in the absence of replication, whereas hemi-methylation of the complementary strand causes a >6.3-fold inhibition of Ds excision. Consistently in the active hemi-methylated state, the Ds ends have a high binding affinity for the transposase, whereas binding to inactive ends is strongly reduced. These results provide strong evidence for the above-mentioned model. Moreover, in the absence of DNA methylation, replication enhances Ds transposition in petunia protoplasts >8-fold and promotes formation of a predominant excision footprint. Accordingly, replication also has a methylation-independent regulatory effect on transposition.
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Metilação de DNA , Replicação do DNA , Elementos de DNA Transponíveis , DNA de Plantas , Transposases , Zea mays/genética , Dano ao DNA , Pegada de DNARESUMO
A novel approach to enhance the activity of doxorubicin is to increase the availability of cellular "chelatable" iron to participate in doxorubicin-mediated free-radical generation. To achieve this, we designed a regimen consisting of desferrioxamine (DFO, 50 mg/kg daily given as an i.v. infusion over 72 h) to increase cellular iron uptake. Thereafter, the combination of iron sorbitol citrate (ISC) and doxorubicin (as a single agent or as part of the CHOP regimen) was given. In a phase I study we investigated the toxicity of this regimen in nine patients with refractory malignant disease. Severe but reversible ocular toxicity (i.e., acute maculopathy) was observed in two patients. As these patients were the only ones who were pretreated with cisplatin, we caution against the use of DFO in cisplatin-pretreated patients. Severe phlebitis was encountered in five of nine patients. A partial remission was observed in two of four patients with refractory Non-Hodgkin's lymphoma who were treated with DFO, ISC, and doxorubicin as part of the CHOP regimen. We conclude that pretreatment with DFO and iron sorbitol citrate may be of benefit in the treatment of malignancies with doxorubicin-containing regimens, but ocular toxicity and severe phlebitis limits the use of DFO in this approach. The attachment of DFO to biocompatible polymers may be a method of overcoming the observed toxicity and warrants further study.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Cítrico , Doxorrubicina/uso terapêutico , Ferro/farmacocinética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citratos/administração & dosagem , Citratos/efeitos adversos , Desferroxamina/administração & dosagem , Desferroxamina/metabolismo , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Combinação de Medicamentos , Sinergismo Farmacológico , Olho/efeitos dos fármacos , Feminino , Compostos Férricos/administração & dosagem , Compostos Férricos/efeitos adversos , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/metabolismo , Masculino , Pessoa de Meia-Idade , Sorbitol/administração & dosagem , Sorbitol/efeitos adversos , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
A data set of 389 compounds, active in the central nervous system (CNS) and divided into eight classes according to the receptor type, was extracted from the RBI database and analyzed by Self-Organizing Maps (SOM), also known as Kohonen Artificial Neural Networks. This method gives a 2D representation of the distribution of the compounds in the hyperspace derived from their molecular descriptors. As SOM belongs to the category of unsupervised techniques, it has to be combined with another method in order to generate classification models with predictive ability. The fuzzy clustering (FC) approach seems to be particularly suitable to delineate clusters in a rational way from SOM and to get an automatic objective map interpretation. Maps derived by SOM showed specific regions associated with a unique receptor type and zones in which two or more activity classes are nested. Then, the modeling ability of the proposed SOM/FC Hybrid System tools applied simultaneously to eight activity classes was validated after dividing the 389 compounds into a training set and a test set, including 259 and 130 molecules, respectively. The proper experimental activity class, among the eight possible ones, was predicted simultaneously and correctly for 81% of the test set compounds.
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Sistema Nervoso Central/efeitos dos fármacos , Técnicas de Química Combinatória , Bases de Dados Factuais , Redes Neurais de Computação , Lógica Fuzzy , Humanos , Preparações Farmacêuticas/classificação , Relação Quantitativa Estrutura-AtividadeRESUMO
The influence of both the design of the product (formulated raw ingredients) and type of product (on the meat type formulated base) on the mineral composition, crude protein (CP), protein digestibility (PD), total dietary fiber (TDF) and phytic acid (FA) contents of meat-based infant beikosts was studied. The product design was the main factor determining the CP, TDF, Ca, Na and K contents, while the type of product was the main factor determining the PD, FA, Zn, Fe and Mn contents. High K and Mn levels were related to high TDF contents. CP and Zn showed a significant relationship but the CP Fe relationship was not significant.
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Automated data classification is an indispensable tool in Drug Design. It allows to select homogeneous training sets or to distinguish compounds with required biological properties. The Kohonen Neural Networks (KNN) suggest new means for classification of biologically interesting compounds. In this paper, first, capabilities of KNN in data dimensionality reduction are presented as compared with the capabilities of Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). The advantages of KNN become evident with increasing data dimensionality and size of the training set. Then, new methods are suggested to evaluate the quality of KNN models. Finally, a case study on chemical and biological data is presented. The database studied includes more than 2000 organophosphorous potent pesticides. The Kohonen maps were obtained which allow to distinguish compounds with different biological behavior.
Assuntos
Redes Neurais de Computação , Preparações Farmacêuticas/classificação , Relação Estrutura-Atividade , Análise por Conglomerados , Modelos QuímicosRESUMO
Kohonen neural networks, also known as Self Organizing Map (SOM), offer a useful 2D representation of the compound distribution inside a large chemical database. This distribution results from the compound organization in a molecular diversity hyperspace derived from a large set of molecular descriptors. Fuzzy techniques based on the "concept of partial truth" reveal to be also a valuable tool for the direct exploitation of chemical databases or SOM. In such cases a fuzzy clustering algorithm is used. In this paper, a complete hybrid system, combining SOM and fuzzy clustering, is applied. As example, a series of olfactory compounds was selected. The complexity of such information is that a same compound may exhibit different odors. It is shown how fuzzy logic helps to have a better understanding of the organization of the compounds. These hybrid systems, using simultaneously SOM and fuzzy clustering, are foreseen as powerful tools for "virtual pre-screening".
Assuntos
Lógica Fuzzy , Redes Neurais de Computação , Relação Quantitativa Estrutura-Atividade , Olfato/fisiologia , Software , Interface Usuário-ComputadorRESUMO
Nodular regenerative hyperplasia (NRH) of the liver is an infrequent entity that is usually diagnosed after the appearance of clinical signs of portal hypertension such as hepatomegaly, splenomegaly or upper gastrointestinal bleeding due to esophageal varices, which are the most frequently found clinical manifestations in NRH. Ascites is a less frequent finding and has always been described in association with other manifestations of portal hypertension. We describe a new case of NRH with atypical presentation in which ascites was the sole clinical manifestation.