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1.
Clin Radiol ; 77(2): 148-155, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34895912

RESUMO

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.


Assuntos
COVID-19/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , SARS-CoV-2/genética , Índice de Gravidade de Doença , Sequenciamento Completo do Genoma , Idoso , COVID-19/mortalidade , COVID-19/virologia , Estudos de Coortes , Cuidados Críticos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Reino Unido , Carga Viral
2.
Sci Rep ; 11(1): 19253, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34584157

RESUMO

Development of anti-drug antibodies (ADAs) can interfere with therapeutic monoclonal antibodies and may lead to drug neutralisation and clinical disease progression. Measurement of circulating drug levels and development of ADAs in the setting of anti-programmed cell death-1 agent pembrolizumab has not been well-studied. Enzyme-linked immunosorbent assays were used to measure pembrolizumab drug level and ADAs in 41 patients with melanoma at baseline, Time-point 1 (3 weeks) and Time-point 2 (21 weeks). Assay results were related to patient demographics and clinical outcome data at 6 months. The median pembrolizumab drug level at 3 weeks was 237 ng/µL and did not correlate with age, sex or body surface area.17/41 patients had an ADA detected at any timepoint, with the highest prevalence at Timepoint 1 (median concentration = 17 ng/µL). The presence of an ADA did not correlate with clinical progression at 6 months. 3/41 (7%) of patients displayed a falling pembrolizumab drug level and rising ADA titre between Timepoint 1 and 2 suggestive of a neutralising ADA. Pembrolizumab drug levels and ADAs can be readily measured. The rates of total and treatment-emergent ADAs may be higher in "real-word" settings than those previously reported. Larger studies are needed to determine effect of neutralising ADAs on long-term clinical outcome.


Assuntos
Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Neutralizantes/sangue , Antineoplásicos Imunológicos/imunologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/farmacocinética , Progressão da Doença , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Melanoma/sangue , Melanoma/imunologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/imunologia , Resultado do Tratamento
3.
Clin Radiol ; 75(8): 599-605, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32593409

RESUMO

AIM: To determine the incidence of possible COVID-19-related lung changes on preoperative screening computed tomography (CT) for COVID-19 and how their findings influenced decision-making. To also to determine whether the patients were managed as COVID-19 patients after their imaging findings, and the proportion who had SARS-CoV2 reverse transcriptionpolymerase chain reaction (RT-PCR) testing. MATERIALS AND METHODS: A retrospective study was undertaken of consecutive patients having imaging prior to urgent elective surgery (n=156) or acute abdominal imaging (n=283). Lung findings were categorised according to the British Society of Thoracic Imaging (BSTI) guidelines. RT-PCR testing, management, and outcomes were determined from the electronic patient records. RESULTS: 3% (13/439) of CT examinations demonstrated findings of classic/probable COVID-19 pneumonia, whilst 4% (19/439) had findings indeterminate for COVID-19. Of the total cohort, 1.6% (7/439) subsequently had confirmed RT-PCR-positive COVID-19. Importantly, all the patients with a normal chest or alternative diagnoses on CT who had PCR testing within the next 7 days, had a negative RT-PCR (92/407). There was a change in surgical outcome in 6% (10/156) of the elective surgical cohort with no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery (2/283). CONCLUSION: There was a 7% (32/439) incidence of potential COVID-19-related lung changes in patients having preoperative CT. Although this altered surgical management in the elective surgical cohort, no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Procedimentos Cirúrgicos Eletivos , Serviço Hospitalar de Emergência , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Reino Unido , Adulto Jovem
4.
J Theor Biol ; 395: 161-173, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-26869214

RESUMO

Multicellular organisms are characterised by role specialisation, brought about by the epigenetic differentiation of their constituent parts. Conventional game theoretic studies of cooperation do not account for this division of labour, nor do they allow for the possibility of the plastic expression of phenotype. We address these issues by extending the notion of cooperative dilemmas to account for such interaction in which heterogeneous roles are advantageous and present an extended dynamical model of selection that allows for the possibility of conditional expression of phenotype. We use these models to investigate systematically when selection will favour an adaptive diversification of roles. We argue that such extensions to models and concepts are necessary to understand the origins of multicellularity and development.


Assuntos
Evolução Biológica , Teoria dos Jogos , Modelos Biológicos
5.
Biol Philos ; 31: 59-79, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26709324

RESUMO

Social evolution theory conventionally takes an externalist explanatory stance, treating observed cooperation as explanandum and the positive assortment of cooperative behaviour as explanans. We ask how the circumstances bringing about this positive assortment arose in the first place. Rather than merely push the explanatory problem back a step, we move from an externalist to an interactionist explanatory stance, in the spirit of Lewontin and the Niche Construction theorists. We develop a theory of 'social niche construction' in which we consider biological entities to be both the subject and object of their own social evolution. Some important cases of the evolution of cooperation have the side-effect of causing changes in the hierarchical level at which the evolutionary process acts. This is because the traits (e.g. life-history bottlenecks) that act to align the fitness interests of particles (e.g. cells) in a collective can also act to diminish the extent to which those particles are bearers of heritable fitness variance, while augmenting the extent to which collectives of such particles (e.g. multicellular organisms) are bearers of heritable fitness variance. In this way, we can explain upward transitions in the hierarchical level at which the Darwinian machine operates in terms of particle-level selection, even though the outcome of the process is a collective-level selection regime. Our theory avoids the logical and metaphysical paradoxes faced by other attempts to explain evolutionary transitions.

6.
J Appl Physiol (1985) ; 112(1): 118-26, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21940844

RESUMO

Reduction in total lung capacity (TLC) in obese men is associated with restricted expansion of the thoracic cavity at full inflation. We hypothesized that thoracic expansion was reduced by the load imposed by increased total trunk fat volume or its distribution. Using MRI, we measured internal and subcutaneous trunk fat and total abdominal and thoracic volumes at full inflation in 14 obese men [mean age: 52.4 yr, body mass index (BMI): 38.8 (range: 36-44) kg/m(2)] and 7 control men [mean age: 50.1 yr, BMI: 25.0 (range: 22-27.5) kg/m(2)]. TLC was measured by multibreath helium dilution and was restricted (<80% of the predicted value) in six obese men (the OR subgroup). All measurements were made with subjects in the supine position. Mean total trunk fat volume was 16.65 (range: 12.6-21.8) liters in obese men and 6.98 (range: 3.0-10.8) liters in control men. Anthropometry and mean total trunk fat volumes were similar in OR men and obese men without restriction (the ON subgroup). Mean total intraabdominal volume was 9.41 liters in OR men and 11.15 liters in ON men. In obese men, reduced thoracic expansion at full inflation and restriction of TLC were not inversely related to a large volume of 1) intra-abdominal or total abdominal fat, 2) subcutaneous fat volume around the thorax, or 3) total trunk fat volume. In addition, trunk fat volumes in obese men were not inversely related to gas volume or estimated intrathoracic volume at supine functional residual capacity. In conclusion, this study failed to support the hypotheses that restriction of TLC or impaired expansion of the thorax at full inflation in middle-aged obese men was simply a consequence of a large abdominal volume or total trunk fat volume or its distribution.


Assuntos
Gordura Abdominal/fisiologia , Composição Corporal/fisiologia , Obesidade/fisiopatologia , Capacidade Pulmonar Total/fisiologia , Antropometria , Humanos , Medidas de Volume Pulmonar , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Obesidade/complicações
7.
J Appl Physiol (1985) ; 108(6): 1605-12, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20299612

RESUMO

Restriction of total lung capacity (TLC) is found in some obese subjects, but the mechanism is unclear. Two hypotheses are as follows: 1) increased abdominal volume prevents full descent of the diaphragm; and 2) increased intrathoracic fat reduces space for full lung expansion. We have measured total intrathoracic volume at full inflation using magnetic resonance imaging (MRI) in 14 asymptomatic obese men [mean age 52 yr, body mass index (BMI) 35-45 kg/m2] and 7 control men (mean age 50 yr, BMI 22-27 kg/m2). MRI volumes were compared with gas volumes at TLC. All measurements were made with subjects supine. Obese men had smaller functional residual capacity (FRC) and FRC-to-TLC ratio than control men. There was a 12% predicted difference in mean TLC between obese (84% predicted) and control men (96% predicted). In contrast, differences in total intrathoracic volume (MRI) at full inflation were only 4% predicted TLC (obese 116% predicted TLC, control 120% predicted TLC), because mediastinal volume was larger in obese than in control [heart and major vessels (obese 1.10 liter, control 0.87 liter, P=0.016) and intrathoracic fat (obese 0.68 liter, control 0.23 liter, P<0.0001)]. As a consequence of increased mediastinal volume, intrathoracic volume at FRC in obese men was considerably larger than indicated by the gas volume at FRC. The difference in gas volume at TLC between the six obese men with restriction, TLC<80% predicted (OR), and the eight obese men with TLC>80% predicted (ON) was 26% predicted TLC. Mediastinal volume was similar in OR (1.84 liter) and ON (1.73 liter), but total intrathoracic volume was 19% predicted TLC smaller in OR than in ON. We conclude that the major factor restricting TLC in some obese men was reduced thoracic expansion at full inflation.


Assuntos
Obesidade/fisiopatologia , Tórax/fisiopatologia , Volume de Ventilação Pulmonar , Capacidade Pulmonar Total , Humanos , Masculino , Pessoa de Meia-Idade
8.
Biochem Soc Trans ; 34(Pt 4): 560-1, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16856860

RESUMO

Whereas spontaneous point mutation operates on nucleotides individually, sexual recombination manipulates the set of nucleotides within an allele as an essentially particulate unit. In principle, these two different scales of variation enable selection to follow fitness gradients in two different spaces: in nucleotide sequence space and allele sequence space respectively. Epistasis for fitness at these two scales, between nucleotides and between genes, may be qualitatively different and may significantly influence the advantage of mutation-based and recombination-based evolutionary trajectories respectively. We examine scenarios where the genetic sequence within a gene strongly influences the fitness effect of a mutation in that gene, whereas epistatic interactions between sites in different genes are weak or absent. We find that, in cases where beneficial alleles of a gene differ from one another at several nucleotide sites, sexual populations can exhibit enormous benefit compared with asexual populations: not only discovering fit genotypes faster than asexual populations, but also discovering high-fitness genotypes that are effectively not evolvable in asexual populations.


Assuntos
Meiose/genética , Recombinação Genética/genética , Animais , Genótipo , Modelos Genéticos , Mutação/genética , Reprodução/genética
9.
Respir Med ; 99(8): 1053-60, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15950148

RESUMO

Progression of chronic obstructive pulmonary disease (COPD) has been studied predominantly by following change in forced expiratory volume in 1s (FEV1) which reflects both primary airway disease and associated alveolar disease. Carbon monoxide transfer (Tlco) (the product of the transfer coefficient Kco and alveolar volume Va) is the only simple, widely available test of alveolar function, but few studies have followed long-term changes in an individual. Seventeen middle-aged men with moderate chronic airflow obstruction (mean FEV1 56% of predicted values) were observed with yearly measurements of FEV1, Tlco and Kco over a mean of 18.9 yr. At the end of follow-up FEV1 had fallen to 29% of predicted values. Va, measured by single breath dilution, fell in each man. Kco at recruitment ranged from 41% to 110% predicted and remained >75% predicted in eight men at the end of follow-up supporting a phenotype of COPD with predominant airway disease and little emphysema. Fall in FEV1 was faster (2.03% predicted FEV1/yr) in seven men with low initial Kco<75% pred. than in men with initial Kco>75% pred. (1.14% predicted FEV1/yr, P=0.006). Repeated measurements of CO transfer in an individual should increase the present poor knowledge of the contribution of alveolar disease to the progression of chronic airflow obstruction.


Assuntos
Monóxido de Carbono/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Antropometria , Testes Respiratórios , Progressão da Doença , Seguimentos , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Alvéolos Pulmonares/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Capacidade Vital
10.
J Appl Physiol (1985) ; 98(2): 512-7, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15475605

RESUMO

Reduced functional residual capacity (FRC) is consistently found in obese subjects. In 10 obese subjects (mean +/- SE age 49.0 +/- 6 yr, weight 128.4 +/- 8 kg, body mass index 44 +/- 3 kg/m2) without respiratory disease, we examined 1) supine changes in total lung capacity (TLC) and subdivisions, 2) whether values of total respiratory resistance (Rrs) are appropriate for mid-tidal lung volume (MTLV), and 3) estimated resistance of the nasopharyngeal airway (Rnp) in both sitting and supine postures. The results were compared with those of 13 control subjects with body mass indexes of <27 kg/m2. Rrs at 6 Hz was measured by applying forced oscillation at the mouth (Rrs,mo) or the nose (Rrs,na); Rnp was estimated from the difference between sequential measurements of Rrs,mo and Rrs,na. All measurements were made when subjects were seated and when supine. Obese subjects when seated had a restrictive defect with low TLC and FRC-to-TLC ratio; when supine, TLC fell 80 ml and FRC fell only 70 ml compared with a mean supine fall of FRC of 730 ml in control subjects. Values of Rrs,mo and Rrs,na at resting MTLV in obese subjects were about twice those in control subjects in both postures. Relating total respiratory conductance (1/Rrs) to MTLV, the increase in Rrs,mo in obese subjects was only partly explained by their reduced MTLV. Rnp was increased in some obese subjects in both postures. Despite the increased extrapulmonary mass load in obese subjects, further falls in TLC and FRC when supine were negligible. Rrs,mo at isovolume was increased. Further studies are needed to examine the causes of reduced TLC and increases in Rrs,mo and sometimes in Rnp in obese subjects.


Assuntos
Resistência das Vias Respiratórias , Medidas de Volume Pulmonar/métodos , Obesidade/fisiopatologia , Postura , Volume de Ventilação Pulmonar , Adaptação Fisiológica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Decúbito Dorsal
11.
J Asthma ; 41(7): 701-7, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15584628

RESUMO

INTRODUCTION: Subjects with asthma frequently have nasal symptoms and complain of orthopnoea but airflow resistance is usually only assessed during oral breathing and while seated. METHOD: We have used a forced oscillation technique to measure total respiratory resistance (Rrs) at 6Hz during mouth breathing (Rrs,mo) and during nose breathing (Rrs,na) in the sitting and supine postures; resistance of the nasal airway (Rnaw) was estimated as Rrs,na--Rrs,mo. Forced oscillations were applied during normal tidal breathing and the mid-tidal lung volume (MTLV) was determined for each breathing route and posture. SUBJECTS: Three groups of subjects were studied: 10 normal subjects without lung or nasal disease (N; five males, mean age 33.5 [range 23-58] years, mean FEV1 105%pred, FEV1/VC 86%); seven subjects with asthma alone (A; four males, 40.3 [23-57] years, mean FEV1 66%pred, FEV1/VC 74%); 10 asthmatic subjects with nasal obstructive symptoms (AN; six males, 62.8 [38-80] years, mean FEV1 56%pred, FEV1/VC 75%). RESULTS: In all three groups of subjects, mean Rrs,mo and Rrs,na were higher in the supine than sitting posture. In normal subjects the increase in supine Rrs,mo was associated with a 0.6 liter fall in MTLV. In asthma supine Rrs,mo increased despite a much smaller fall in MTLV; supine increases in Rrs,na were particularly large in presence of nasal disease. DISCUSSION: Values of airflow resistance are 2-3 times higher in both normal and asthmatic subjects when breathing via the nose and supine than under normal laboratory conditions of oral breathing and seated.


Assuntos
Resistência das Vias Respiratórias/fisiologia , Asma/fisiopatologia , Nariz/fisiopatologia , Respiração , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca , Projetos Piloto , Postura , Valores de Referência , Mecânica Respiratória , Sensibilidade e Especificidade
12.
J Endourol ; 18(2): 167-71, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15072625

RESUMO

BACKGROUND AND PURPOSE: Differentiation of recurrent neoplasm and desmoplastic reaction following laparoscopic resection of renal mass lesions poses a problem. The usefulness of multiphasic helical CT-generated criteria based on enhancement and morphologic characteristics was investigated. PATIENTS AND METHODS: The findings in 5 female and 12 male patients aged 29 to 68 years having renal-cell carcinoma (11-38 mm; N = 15) or solitary angiomyolipomas (N = 2) treated by laparoscopic resection (N = 15) or open segmental surgery (N = 2) were analyzed. Multiphasic helical CT was performed in the preenhancement, arterial corticomedullary, parenchymal, and excretory phases generating 2.5- to 7-mm slices. RESULTS: Both recurrent neoplasms showed median postcontrast enhancement of 119 HU in the arterial corticomedullary phase; the median enhancement of desmoplastic masses was 48 HU. In the parenchymal and excretory phase, recurrent neoplasms showed progressive loss of enhancement, whereas desmoplastic lesions sustained enhancement at about the same level. Recurrent neoplasms presented a defined mass with characteristic spiculation, whereas desmoplastic reaction was characterized by an ill-defined mass with spidery projections extending to abutting fat and residual fascial planes. On 2- to 3-month follow-up scans, recurrent neoplasms showed progressive increases in size and desmoplastic reaction a sharp decrease. CONCLUSION: Enhancement of the mass at the operative site on arterial corticomedullary-phase CT to >90 HU strongly suggests recurrent renal-cell carcinoma, while progressive decrease in size on 1- to 3-month follow-up CT suggests a desmoplastic reaction.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Fibrose/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Nefrectomia/efeitos adversos , Tomografia Computadorizada Espiral , Adulto , Idoso , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Feminino , Fibrose/etiologia , Fibrose/patologia , Humanos , Neoplasias Renais/patologia , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
13.
J Endourol ; 18(1): 49-56, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15006054

RESUMO

PURPOSE: The feasibility of identifying early manifestations of renal papillary necrosis (RPN) and medullary necrosis (RMN) on multiphasic helical CT, leading to prompt treatment for the causative conditions, and its impact on reducing the incidence of late-stage RML and RPN, was investigated. PATIENTS AND METHODS: Sixty-eight patients (35 male, 33 female) aged 19 to 88 years were examined by multiphasic helical CT for complaints of microscopic hematuria (N=49), macroscopic hematuria (N=2), bacteriuria (N=45), pyuria (N=10), fever (N=15), and flank pain (N=27). Preenhancement, arterial corticomedullary, parenchymal, and excretory phase scans generated 1.25 to 7-mm-thick slices. Follow-up CTs were performed at 1 month (N=62) and 3 months (N=58). RESULTS: While the attenuation coefficients of areas suspect for RMN and RPN were similar on preenhancement CT, they differed substantially on the arterial corticomedullary phase (lesions 55 HU mean; normal medulla 120 HU mean) and parenchymal phase (lesions 58 HU mean, normal medulla 210 HU mean). Investigation for predisposing conditions identified diabetes in 18 patients, upper urinary-tract infections in 48, sickle-cell disease or trait in 17, urinary obstruction in 7, and cirrhosis of the liver in 1. On follow-up examinations, enhancement had normalized in 26 compromised areas of 14 patients at 1 month, and 47 areas (23 patients) at 3 months, remained stationary in 28 patients at 1 month and 9 at 3 months, and progressed in 20 at 1 and 26 at 3 months (P<0.001; Fisher's exact test). Patients (N=35) treated for underlying conditions causing ischemia showed reperfusion in 12 cases at 1 month and 20 at 3 months, while of the untreated patients (N=10), none showed reperfusion, and all lesions increased in size. CONCLUSIONS: Multiphasic helical CT is recommended for identification of RMN and RPN at a stage when effective treatment of underlying causative conditions can arrest or reverse the process of devascularization and prevent loss of medullary tissue.


Assuntos
Medula Renal/patologia , Necrose Papilar Renal/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriúria/diagnóstico por imagem , Complicações do Diabetes , Seguimentos , Hematúria/diagnóstico por imagem , Humanos , Medula Renal/irrigação sanguínea , Medula Renal/diagnóstico por imagem , Necrose Papilar Renal/etiologia , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Necrose , Piúria/diagnóstico por imagem , Traço Falciforme/complicações , Infecções Urinárias/complicações
14.
J Urol ; 170(1): 94-8, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12796654

RESUMO

PURPOSE: Multiphasic helical computerized tomography (CT) is advocated to identify early manifestations of papillary and medullary necrosis based on decreased enhancement of circumscribed areas in the medullary pyramid. At this stage the devascularizing process can be reversed if causative conditions such as infections or diabetes mellitus are effectively treated. MATERIALS AND METHODS: Multiphasic helical CTs were performed in 31 male and 26 female patients with complaints of microscopic hematuria (41), macroscopic hematuria (2), bacteriuria (39) and pyuria (9). Pre-enhancement, arterial, early corticomedullary, parenchymal and excretory phase helical CTs generated 1.25 to 5 mm. thick slices. Followup examination included multiphasic helical CT at 1 and 3 months, and excretory urography for some patients at 3 months. RESULTS: Bacteriuria was identified as the probable cause of medullary and papillary necrosis in 39 patients, of whom 28 were treated with effective antibiotic therapy, resulting in normalization and re-perfusion of the initial lesion in 16, no change in 5 and progressive disease in 7 at 3-month followup. Of 8 lesions not treated with specific antibiotic therapy 4 progressed and 4 remained unchanged. CONCLUSIONS: Multiphasic helical CT unlike the excretory urogram can identify medullary and papillary necrosis at an early stage when effective treatment of the underlying cause can reverse the process of devascularization and prevent sloughing of medullary tissues.


Assuntos
Bacteriúria/complicações , Rim/diagnóstico por imagem , Rim/patologia , Tomografia Computadorizada Espiral , Adulto , Feminino , Hematúria/etiologia , Humanos , Rim/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Necrose , Intensificação de Imagem Radiográfica
16.
J Urol ; 167(5): 2100-3; discussion 2103-4, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11956449

RESUMO

PURPOSE: We confirmed clinically whether chemo-ablation of the prostate with absolute ethanol may be an innovative transurethral approach for the relief of obstructive benign prostatic hyperplasia. METHODS: Using the InjecTx endoscopic device (Injectx Inc., San Jose, California) an initial cohort of 15 patients, including 13 who have now been followed more than 1 year, underwent elective transurethral chemo-ablation of the prostate. RESULTS: Preoperative and postoperative comparisons of the American Urological Association symptom score, maximum urine flow rate and prostatic volume reveal significant improvement with minimal discomfort and no major complication. CONCLUSIONS: The InjecTx technique proved encouragingly successful in this initial small-scale clinical trial.


Assuntos
Etanol/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Cistoscópios , Desenho de Equipamento , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Urodinâmica/efeitos dos fármacos
17.
BMC Cancer ; 1: 19, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11710966

RESUMO

BACKGROUND: STAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic. METHODS: We looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells. RESULTS: Although both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells. CONCLUSIONS: We conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Interleucina-6/fisiologia , Hiperplasia Prostática/patologia , Neoplasia Prostática Intraepitelial/patologia , Proteínas Proto-Oncogênicas , Transdução de Sinais/fisiologia , Transativadores/fisiologia , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Proteínas de Ligação a DNA/química , Dexametasona/farmacologia , Inibidores Enzimáticos/farmacologia , Células Epiteliais/química , Células Epiteliais/enzimologia , Interleucina-6/biossíntese , Janus Quinase 2 , Masculino , Fenótipo , Fosforilação , Hiperplasia Prostática/enzimologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasia Prostática Intraepitelial/enzimologia , Neoplasia Prostática Intraepitelial/genética , Neoplasia Prostática Intraepitelial/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , Ratos , Receptores de Interleucina-6/biossíntese , Fator de Transcrição STAT3 , Transativadores/química , Células Tumorais Cultivadas , Tirfostinas/farmacologia
18.
J Endourol ; 14(7): 583-7, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11030541

RESUMO

PURPOSE: This retrospective analysis assessed the efficacy of balloon dilatation, endoureterotomy, percutaneous ureteroneocystostomy with stenting, and insertion of Wallstents in the management of malignant ureteral strictures with an intact or compromised vascular supply. PATIENTS AND METHODS: A series of 127 patients with ureteral strictures secondary to malignancies were assessed after at least 2-year follow-up (range 2-5 years; mean 3.5 years). Balloon dilation (antegrade approach) was applied in 46 patients, endoureterotomy with temporary stenting in 37, percutaneous ureteroneocystostomy with stenting in 34, bougie and stents in 13, and Wallstents in 31. RESULTS: Balloon dilatation was successful in only two of four malignant midureteral stenoses with intact vascular supplies and was even less successful (10%) in midureteral strictures with a compromised vascular supply. Endoureterotomy failed in all cases to prevent ureteral obstruction. Percutaneous ureteroneocystostomy achieved patency in 11 of 34 patients (33%) having a compromised ureteral vascular supply. Wallstents were successful in 18 of 31 patients (58%) with stenoses of the pelvic ureter. CONCLUSIONS: Percutaneous ureteroneocystostomy with stenting meets the requirement for palliation in patients with obstruction secondary to pelvic neoplasms. Wallstents proved to be most successful when used in the pelvic ureter.


Assuntos
Cateterismo , Cistostomia , Stents , Ureter/cirurgia , Obstrução Ureteral/terapia , Ureterostomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Urology ; 55(5): 652-7, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10792072

RESUMO

OBJECTIVES: To retrospectively assess the efficacy of balloon dilation, endopyelotomy/ureterotomy, and stenting alone in the management of benign ureteral strictures with intact or compromised vascular supply. METHODS: One hundred fourteen patients with benign ureteral strictures were assessed after at least a 2-year follow-up (range 2 to 16 years, mean 6.3). Balloon dilation was performed in 81, endopyelotomy/ureterotomy with temporary stenting in 27, and ureteral stenting alone in 6 patients. Ureteral strictures were divided into strictures with intact or with compromised vascular supply. RESULTS: Balloon dilation was successful in short ureteral strictures with intact vascular supply in 33 of 37 (89.2%), but only in 3 of 8 (37.5%) long ureteral strictures and in 1 of 2 (50%) recurrent ureteropelvic junction strictures. Balloon dilation was less successful when the vascular supply was compromised in 2 (40%) of 5 short strictures, 1 (16.7%) of 6 long strictures, and 2 (33.3%) of 6 recurrent ureteropelvic junction strictures. Endopyelotomy/ureterotomy was successful in 17 (89.5%) of 19 strictures with compromised vascular supply. CONCLUSIONS: Balloon dilation is recommended for management of short strictures with intact vascular supply. Endoureterotomy with stenting is recommended for all long ureteral strictures, for ureteropelvic junction stenoses, and for short ureteral strictures with compromised vascular supply and benign underlying etiology.


Assuntos
Obstrução Ureteral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Ureter/irrigação sanguínea , Obstrução Ureteral/complicações , Ureteroscopia
20.
Urology ; 55(3): 348-52, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10699608

RESUMO

OBJECTIVES: To define the accuracy, safety, and impact of percutaneous biopsies of indeterminate mass lesions as an additional diagnostic tool. The vast majority of renal mass lesions are routinely diagnosed by radiographic features alone. However, with the increased use of computed tomography scanning and ultrasound, many smaller renal masses, which are "indeterminate" (refractory to categorization on the basis of imaging alone), are now being discovered. METHODS: We retrospectively reviewed 583 patients (364 male and 219 female) with indeterminate renal mass lesions diagnosed by imaging studies that were further investigated by percutaneous biopsy. Patients were followed up for at least 5 years if the biopsy result demonstrated a benign lesion, or they underwent surgical exploration if the biopsy result demonstrated a malignancy. Biopsy or aspiration material was assessed by histopathologic and cytologic evaluation and, when appropriate, with biochemistry, Gram stain, culture, and sensitivity. The biopsy site was localized by computed tomography, ultrasound, or fluoroscopy. RESULTS: Five hundred eighty-three patients with indeterminate renal mass lesions (representing 7.2% of all renal masses diagnosed from 1967 through 1996) were diagnosed by imaging studies complemented by guided biopsy. Sixty-six patients were lost to follow-up, leaving 517 patients who were analyzed. In 393 cases (76%), the imaging-guided biopsy provided a definitive diagnosis. The incidence of false diagnoses was 1.2% (7 biopsies). In 124 of the cases (21%), imaging-guided biopsy was unable to determine the etiology of the lesion with acceptable confidence; of these, 21 biopsies did not provide enough material to establish the diagnosis (16.9%). CONCLUSIONS: Overall, percutaneous biopsy of the kidney has proved to be a safe and accurate diagnostic procedure, with impact on the management of cystic or solid renal lesions.


Assuntos
Biópsia por Agulha , Rim/patologia , Radiografia Intervencionista , Ultrassonografia de Intervenção , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/métodos , Erros de Diagnóstico , Feminino , Fluoroscopia , Humanos , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
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