RESUMO
Myeloproliferative neoplasms (MPNs) are malignant disorders originating from clonal expansion of a single neoplastic stem cell and characteristically show an increase in bone marrow reticulin fibers. Lysyl oxidases (LOXs) are copper-dependent amine oxidases that play a critical role in the biogenesis of connective tissue by crosslinking extracellular matrix proteins, collagen and elastin. Expression of LOX gene family members is increased in disorders associated with increased fibrosis. To evaluate involvement of LOX gene family in various MPNs. In-situ hybridization was used to detect Lysyl-Oxidase family members in bone marrow biopsies from patients with different MPNs. We compared normal bone marrows and those from patients with polycythemia vera, essential thrombocythemia, chronic myeloid leukemia, and primary myelofibrosis (PMF). Serum levels of lysyl-oxidase from patients with PMF and healthy controls were also examined. LOX gene family was not detected in normal bone marrows. All members of the LOX gene family were over expressed in PMF. In other MPNs a differential pattern of expression was observed. Differences in gene expression were statistically significant (P < 0.010). The medianserum LOX levels in normal controls was 28.4 ± 2.5 ng\ml and 44.6 ± 9.44 ng\ml in PMF (P = 0.02). The varying pattern of expression of LOX genes may reflect differences in the pathophysiology of bone marrow fibrosis in these MPNs. These observations could be used as the basis for future targeted therapy directed against bone marrow fibrosis.
Assuntos
Aminoácido Oxirredutases/metabolismo , Medula Óssea/metabolismo , Regulação Neoplásica da Expressão Gênica , Transtornos Mieloproliferativos/metabolismo , Proteína-Lisina 6-Oxidase/metabolismo , Aminoácido Oxirredutases/sangue , Aminoácido Oxirredutases/genética , Medula Óssea/enzimologia , Medula Óssea/patologia , Estudos de Coortes , Fibrose , Humanos , Processamento de Imagem Assistida por Computador , Hibridização In Situ , Isoenzimas/genética , Isoenzimas/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/patologia , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Policitemia Vera/enzimologia , Policitemia Vera/metabolismo , Policitemia Vera/patologia , Mielofibrose Primária/enzimologia , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia , Proteína-Lisina 6-Oxidase/sangue , Proteína-Lisina 6-Oxidase/genética , RNA Mensageiro/metabolismo , Trombocitemia Essencial/enzimologia , Trombocitemia Essencial/metabolismo , Trombocitemia Essencial/patologiaRESUMO
Even though pathologists are trained to recognize the same histological features for the diagnosis and grading of different histological images, not all pathologists are influenced to a similar level of intensity by the same morphological characteristics of the tissue when scoring Barrett's dysplasia/neoplasia. The variables which most pathologists have intuitively chosen to use for scoring of the severity of Barrett's changes are mainly those related to the general tissue architecture, such as nuclear crowding, orientation and stratification. Interestingly, nuclear size is not used by most pathologists but nuclear pleomorphism and symmetry does influence a significant number of pathologists. Maybe the most difficult variables for the human eye to recognize are variables of chromatin texture (such as margination or heterogeneity), the predictive importance of which has been demonstrated in a previously published work. Textural variables may therefore remain the subject of a computerized analysis. Nevertheless, the fact that a few pathologists do actually correlate with nuclear texture in scoring, argues in favor of making further attempts to train pathologists to also rely on texture, similar to cytologists, when scoring Barrett's dysplasia.
Assuntos
Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Lesões Pré-Cancerosas/patologia , Biópsia , Cromatina/patologia , Diagnóstico por Computador , Esôfago/patologia , Humanos , Processamento de Imagem Assistida por Computador , Gradação de Tumores , Invasividade Neoplásica/patologia , Estatística como AssuntoRESUMO
BACKGROUND AND OBJECTIVES: Neuropilin-1 (NP-1), a functional vascular endothelial growth factor (VEGF) receptor, is important in the priming of resting T cells and contributes to the development of peripheral tolerance. Semaphorins, a family of axon guidance molecules, has been found to be involved in regulating the immune system. The aim of this study was to explore the involvement of NP-1 and semaphorins in lupus glomerulonephritis (LGN). METHODS: Twelve kidney biopsies from LGN patients and five normal biopsies were examined in this study. In addition, eight biopsies from patients with primary nephropathy and proteinuria were included serving as a disease control group. Biopsies were stained with anti-VEGF, NP-1, and semaphorins. The Image Pro-Plus software was used to measure the intensity and extent of staining. The correlation with clinico-pathological parameters was evaluated. RESULTS: VEGF expression was slightly higher in LGN. NP-1 and semaphorins were stained with significantly higher intensity in LGN when compared with both the normal and the disease control groups. NP-1 deposits were found only in damaged glomerulus areas and positively correlated with clinico-pathological parameters of renal disease (a statistical trend). However, the semaphorins were found in inverse correlations. DISCUSSION: Being present in normal and slightly increased in diseased glomeruli, VEGF is considered protective during inflammation. Increased NP-1 expression in LGN may intensify the possible protective effect of VEGF, thereby preventing endothelial damage. However, one should consider the possibility that increased NP-1 expression is harmful and could play a role in the damage of LGN. NP-1 is suggested to be a reliable marker differentiating focal versus diffuse LGN. Semaphorin 3A can serve as a histological marker for tubular damage. The altered ability of kidneys to secrete semaphorins during advanced renal damage may in part explain its inverse correlation with renal function. Further work is needed in order to better understand the role of NP-1 and semaphorins in LGN.
Assuntos
Nefrite Lúpica/imunologia , Neuropilina-1/metabolismo , Semaforinas/metabolismo , Estudos de Casos e Controles , Humanos , Rim/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Complete histopathologic tumor regression after neoadjuvant treatment is a well-known prognostic factor for survival among patients with adenocarcinomas of the esophagus and gastroesophageal junction. The aim of this international Delphi survey was to reach a consensus regarding the most useful tumor regression grading (TRG) system that could represent an international standard for histopathologic TRG grading of gastroesophageal carcinomas. Fifteen pathologists with special interest in esophageal and gastric pathology participated in the online survey. The initial questionnaire contained of 43 statements that addressed the following topics: (1) specimen processing, (2) gross examination, (3) cross sectioning, (4) staining, (5) Barrett's esophagus, (6) TRG systems, and (7) TRG in lymph node (LN). Participants rated the items using a 5-point Likert style scale and were encouraged to write comments for each statement. The expert panel recommended a 4-tiered TRG system for assessing the primary tumor: grade 1: No residual tumor (complete histopathologic tumor regression), grade 2: less than 10% residual tumor (near-complete regression), grade 3: 10%-50% residual tumor (partial regression), grade 4: greater than 50% residual tumor (minimal/no regression), combined with a 3-tiered system for grading therapeutic response in metastatic LNs: grade a: no residual tumor (complete histopathologic TRG), grade b: partial regression (tumor cells and regression), grade c: no regression (no sign of tumor response). This TRG grading system can be recommended as an international standard for histopathologic TRG grading in esophageal and gastroesophageal junction adenocarcinoma.
Assuntos
Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Gradação de Tumores/métodos , Adenocarcinoma/terapia , Consenso , Técnica Delphi , Neoplasias Esofágicas/terapia , Humanos , Terapia Neoadjuvante/métodos , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Resultado do TratamentoRESUMO
One key cell-signaling event central to inflammation in kidney diseases, including chronic renal allograft dysfunction or disease (CRAD), is the activation of NF-kappaB, which controls transcription of numerous proinflammatory mediators. Glycogen synthase kinase (GSK) 3beta is an indispensable element of NF-kappaB activation, however, the exact role of GSK3beta in the pathogenesis of inflammatory kidney diseases like CRAD is uncertain and was examined. Immunohistochemistry staining of GSK3beta was weak in normal kidneys, but was markedly induced in inflamed allograft kidneys, with prominent cytoplasmic staining of tubular cells in areas of inflammation. Net GSK3beta activity is regulated by inhibitory phosphorylation of its serine 9 residue, and this occurred in CRAD. Thus, the magnitude of GSK3beta inactivation was inversely correlated with the degree of injury as assessed by Banff criteria. In vitro in cultured human tubular epithelial cells, GSK3beta overexpression augmented, while GSK3beta silencing diminished proinflammatory cellular responses to TNF-alpha stimulation, including NF-kappaB activation and expression of chemokines MCP-1 and RANTES. These inflammatory responses were obliterated by GSK3beta inhibitors. Collectively, GSK3beta plays an important role in mediating proinflammatory NF-kappaB activation and renal inflammation. Suppression of GSK3beta activity might represent a novel therapeutic strategy to treat CRAD.
Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Inflamação/metabolismo , Falência Renal Crônica/metabolismo , Transplante de Rim/efeitos adversos , Transplante de Rim/patologia , Biomarcadores/metabolismo , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Imuno-Histoquímica , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/enzimologia , Túbulos Renais Proximais/metabolismo , NF-kappa B/metabolismo , Transplante Homólogo/efeitos adversosRESUMO
AIMS: Periventricular white matter injury in premature infants occurs following hypoxia/ischaemia and systemic infection, and results in hypomyelination, as well as neuromotor and cognitive deficits later in life. Inflammatory infiltrates are seen within human cerebral white matter from periventricular leucomalacia (PVL) cases. METHODS: In this study, we examine the time course of CD-68+ microglial cell responses relative to cell death within white matter following hypoxia/ischaemia in a rat model of PVL. We also tested the efficacy of the minocycline, an agent that suppresses microglial activation, in this model when administered as a post-insult treatment. RESULTS: We show that preoligodendrocyte injury in the post-natal day 6 begins within 24 h and continues for 48-96 h after hypoxia/ischaemia, and that microglial responses occur primarily over the first 96 h following hypoxia/ischaemia. Minocycline treatment over this 96 h time window following the insult resulted in significant protection against white matter injury, and this effect was concomitant with a reduction in CD-68+ microglial cell numbers. CONCLUSIONS: These results suggest that anti-inflammatory treatments may represent a useful strategy in the treatment of PVL, where clinical conditions would favour a post-insult treatment strategy.
Assuntos
Hipóxia-Isquemia Encefálica/prevenção & controle , Leucomalácia Periventricular/complicações , Leucomalácia Periventricular/fisiopatologia , Microglia/patologia , Minociclina/uso terapêutico , Tegmento Mesencefálico/lesões , Animais , Animais Recém-Nascidos , Morte Celular , Modelos Animais de Doenças , Humanos , Hipóxia Encefálica/patologia , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/patologia , Recém-Nascido , Leucomalácia Periventricular/patologia , Microglia/efeitos dos fármacos , Proteína Básica da Mielina/metabolismo , Ratos , Ratos Long-Evans , Tegmento Mesencefálico/patologiaRESUMO
The objective of this study was to evaluate the utility of measuring microvessel fractal dimension (MFD) as a parameter of architectural microvascular complexity in localized renal cell carcinoma (RCC). Forty-nine patients with low-stage clear cell RCC were assessed in a 9-year follow-up retrospective study. Tumor vessels were visualized with the endothelial marker CD34. Tumor microvessel density (MVD) was measured by computerized morphometry. Fractal analysis of the RCC microvascular network was performed and the MFD was computed in each case. Correlation between tumor vascular parameters, histological grade, extent of tumor necrosis and patient survival were tested by uni- and multivariate analyses. A significant correlation was found between tumor grade and decreased survival (P = 0.04). The extent of macroscopic tumor necrosis also significantly correlated with poor prognosis (P = 0.0001). Survival analysis revealed a significantly higher MVD in patients who survived longer than 5 years as compared with those who died before the end of the 5-year follow-up period (MVD = 10.8 +/- 4.7% versus 6.4 +/- 3.7%; P = 0.03). MVD was also inversely associated with the extent of tumor necrosis (P = 0.03). Microvessel fractal dimension was significantly higher in low- as compared with high-grade tumors (1.55 +/- 0.11 versus 1.45 +/- 0.15; P = 0.03). Survival analysis revealed a significantly higher MFD in those who lived >5 years as compared with those who died earlier (1.56 +/- 0.11 versus 1.46 +/- 0.15; P = 0.02). The MFD was inversely associated with the extent of tumor necrosis (P = 0.01). Multivariate analysis revealed that the MFD was the only significant factor to correlate with tumor necrosis, and that tumor necrosis was the only independent predictor of patient survival. These results indicate that the analysis of MFD as a marker of tumor microvascular complexity may provide important prognostic information as well as novel insight into the biology of tumor angiogenesis.
Assuntos
Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/patologia , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/patologia , Microcirculação/patologia , Idoso , Antígenos CD34/biossíntese , Carcinoma de Células Renais/mortalidade , Endotélio Vascular/metabolismo , Feminino , Fractais , Humanos , Imuno-Histoquímica , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Necrose , Prognóstico , Fatores de TempoRESUMO
OBJECTIVES: This study was undertaken to investigate the correlation, which has not been previously investigated, between levels of tumour necrosis factor-alpha (TNF) and levels of pH, glucose, and lactate dehydrogenase (LDH) in pleural fluid of patients with uncomplicated parapneumonic effusion (UCPPE), and patients with complicated parapneumonic effusion (CPPE). METHODS: Using a commercially-available high sensitivity ELISA kit, levels of TNF were measured in pleural fluid of patients with UCPPE (n = 23), and CPPE (n = 15), and were compared with levels of pH, glucose, and LDH in these two groups. RESULTS: The mean +/- SD values of pleural fluid TNF, pH, glucose, and LDH in the UCPPE group were 11.05 +/- 7.65 pg/ml, 7.41 +/- 0.08, 125 +/- 48 mg/dl, and 306 +/- 182 IU/l, respectively. In the CPPE group the values were 56.07 +/- 28.5 pg/ml, 6.82 +/- 0.25, 42 +/- 36 mg/dl, and 2096 +/- 1916 IU/l, respectively. The only significant correlation, which was negative, was found between levels of TNF and pH in the CPPE group (r = -0.62, P = 0.01). Levels of pleural fluid TNF and LDH were significantly higher, and levels of glucose were significantly lower in the CPPE group than in the UCPPE group (P < 0.0001). CONCLUSIONS: This study demonstrates, for the first time that TNF levels correlate inversely with levels of pH in pleural fluid of patients with CPPE but not of patients with UCPPE. This correlation may, in part, explain the pathophysiology of the pleural complications which occur in the presence of CPPE.
Assuntos
Glucose/metabolismo , L-Lactato Desidrogenase/metabolismo , Derrame Pleural/metabolismo , Pneumonia Bacteriana/complicações , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Derrame Pleural/química , Derrame Pleural/etiologiaRESUMO
PURPOSE: To examine the prevalence of anticardiolipin antibodies (ACLA) in relatively young patients with acute myocardial infarction (MI) and their role in subsequent coronary and thromboembolic events in the post-MI period. PATIENTS AND METHODS: In 124 relatively young survivors (aged 65 or younger) of acute MI, ACLA were measured in a controlled prospective study on admission and 3 months later. Myocardial reinfarction and thromboembolic events during a mean follow-up period of 19 +/- 3 months were diagnosed by standard tests. RESULTS: Seventeen (14%) of the 124 patients were ACLA positive (either IgM or IgG) upon admission compared with 2 out of 76 (3%) of the control group matched for age and coronary risk factors (P < 0.01). The levels of ACLA remained unchanged in all but 1 patient 3 months later. During the follow-up period the rate of thromboembolic events and myocardial reinfarction was significantly higher in the ACLA-positive patients as compared with the ACLA-negative group: 41% versus 4% (P < 0.0001) and 35% versus 10% (P < 0.05), respectively. Using logistic regression, high titer of ACLA was found to be the only independent risk factor for subsequent thromboembolic events or myocardial reinfarction after acute MI. CONCLUSIONS: High prevalence of ACLA was found in relatively young survivors of acute MI. The presence of ACLA is a marker for increased risk of subsequent myocardial reinfarction and thromboembolic events after acute MI.
Assuntos
Anticorpos Anticardiolipina/análise , Infarto do Miocárdio/imunologia , Adulto , Idoso , Feminino , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Embolia e Trombose Intracraniana/etiologia , Modelos Logísticos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Estudos Prospectivos , Embolia Pulmonar/etiologia , Fatores de RiscoRESUMO
A series of mercaptoacyl amino acids and related compounds was synthesized and evaluated for inhibition of angiotensin-converting enzyme (ACE) in order to determine the nature and importance of the putative interaction between ACE and the amide moiety of inhibitors such as captopril (3-mercapto-2-methylpropanoyl-L-proline). It was concluded that the interaction involves a hydrogen bond from a donor site on ACE to the oxygen of the amide carbonyl. Compounds in which the amide moiety is replaced by other groups (ester, ketone, sulfonamide) capable of accepting a hydrogen bond are effective inhibitors, but compounds in which only the geometrical features of the amide are retained are ineffective inhibitors. The presence of an NH group is not necessary for effective inhibition. The activity of a series of mercaptoacyl cycloalkyl carboxylic acids parallels the activity of the isosteric series of mercaptoacyl imino acids.
Assuntos
Aminoácidos Sulfúricos/síntese química , Inibidores da Enzima Conversora de Angiotensina , Aminoácidos Sulfúricos/farmacologia , Animais , Fenômenos Químicos , Físico-Química , Ligação de Hidrogênio , Técnicas In Vitro , Pulmão/enzimologia , Conformação Molecular , Coelhos , Relação Estrutura-AtividadeRESUMO
A variant of the protracted tilt test, the 10-minute supine -30-minute tilt test (10S-30TT), has been proposed by us for the evaluation of blood pressure (BP). The present investigation compares parameters of diastolic BP by 3 methods: office measurements, 10S-30TT, and 24-hour ambulatory monitoring; the last method served as a reference standard. Twenty patients presenting at the office with diastolic BP values ranging from 80 to 120 mm Hg (median 90) were studied. Statistically significant correlations were observed between the following parameters: diastolic office BP and average ambulatory awake diastolic BP (r = 0.64, p = 0.002); average tilt-test diastolic BP and average ambulatory awake diastolic BP (r = 0.69, p = 0.0006); frequency of elevated diastolic BP values during the tilt test and frequency of elevated ambulatory awake diastolic BP values (r = 0.69, p = 0.0007). Diastolic BP diagnosis scores exhibited strong correlation only between the ambulatory and tilt-test diagnosis (kappa = 0.70), but not between ambulatory and office BP diagnosis (kappa = 0.50). Based on the close correlation between results of the 10S-30TT and ambulatory monitoring in the evaluation of diastolic BP, we suggest that the faster and cheaper tilt test may serve as a substitute in certain categories of patients.
Assuntos
Monitores de Pressão Arterial , Hipertensão/diagnóstico , Teste da Mesa Inclinada , Adulto , Idoso , Determinação da Pressão Arterial , Diástole , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Postura , Fatores de TempoRESUMO
Captopril is a remarkably effective new antihypertensive drug designed and developed as a potent and specific inhibitor of angiotensin-converting enzyme, a zinc metallopeptidase that participates in the synthesis of a hypertensive peptide, angiotensin II, and in the degradation of a hypotensive peptide, bradykinin. Earlier studies with a snake venom peptide (teprotride or SQ 20881) that could be administered only by injection demonstrated that specific inhibitors of angiotensin-converting enzyme could be highly effective as antihypertensive drugs, and helped to clarify the specificity and mechanism of action of the enzyme. A hypothetical model of the active center of angiotensin-converting enzyme based on its presumed analogy to the well characterized zinc metallopeptidase carboxypeptidase A was used to guide logical sequential improvements of a weakly active prototype inhibitor that led eventually to the highly optimized structure of captopril. The hypothetical working model of the active site of angiotensin-converting enzyme used to develop captopril continues to provide a firm basis for development of new types of specific inhibitors of this biologically important enzyme.
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Animais , Pressão Sanguínea , Captopril/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Peptidil Dipeptidase A/fisiologia , Prolina/análogos & derivados , Prolina/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Succinatos/uso terapêutico , Teprotida/uso terapêuticoRESUMO
Second-semester ultrasonography of a female fetus documented short femora and humeri and dislocation of the radii. Based on the clinical and postmortem radiological findings, autosomal-recessive omodysplasia was diagnosed. The physeal plates of the long tubular bones were assessed by computer-assisted image analysis. The dimensions and orientation of the chondrocytic lacunae in the physeal plates of the omodysplastic fetus were compared with those in the physeal plates of fetuses without gross limb abnormalities (oligohydramnios, n = 2; hydrocephalus, n = 2; Down syndrome, n = 1). The pathological characteristics of the omodysplastic physeal plates were an expanded zone of proliferating cartilage and an increased number of closely packed, small chondrocytes. We propose that a genetic, functional deficiency of the physeal cells, underlying the short-limbed dwarfism of autosomal-recessive omodysplasia, is partially compensated, albeit ineffectively, by an increased number of small chondrocytes in the proliferating zone of the physeal plate.
Assuntos
Osso e Ossos/patologia , Lâmina de Crescimento/patologia , Osteocondrodisplasias/diagnóstico , Ultrassonografia Pré-Natal , Aborto Terapêutico , Adulto , Osso e Ossos/diagnóstico por imagem , Síndrome de Down/patologia , Feminino , Feto/diagnóstico por imagem , Humanos , Hidrocefalia/patologia , Oligo-Hidrâmnio/patologia , Osteocondrodisplasias/patologia , Gravidez , Segundo Trimestre da Gravidez , RadiografiaRESUMO
OBJECTIVES: To compare the hemodynamic and ventilatory responses to autonomic challenge evoked by upright tilt table testing in patients with chronic fatigue syndrome (CFS) to healthy individuals. METHODS: Thirty-two consecutive patients with CFS and 32 healthy volunteers were evaluated with the aid of the recently introduced capnography head-up tilt test (CHUTT). The main outcome measures were values of blood pressure (BP), heart rate (HR), respiratory rate (RR), and end-tidal pressure of co2 (ETPco2) recorded during recumbence and tilt. In addition, the end points of vasodepressor and cardioinhibitory reactions, hyperventilation (defined by ETPco2 <25 mm Hg) and the postural tachycardia syndrome, were recorded. RESULTS: The BP, HR, RR, and ETPco2 recorded during recumbence were similar in both groups. During tilt, patients with CFS developed significantly lower systolic BP, diastolic BP, and ETPco2, and a significant rise in HR and RR (P<.01). In CFS patients, the postural tachycardia syndrome occurred in 44%, vasodepressor reaction in 41%, cardioinhibitory reaction in 13%, and hyperventilation in 31% of cases. One or more end points of the CHUTT were reached in 78% of patients with CFS but in none of the controls (P<.0001). CONCLUSIONS: In most patients with CFS, a spectrum of abnormal homeostatic reactions is diagnosed with the aid of the CHUTT. Data provided by the CHUTT may reinforce the clinical diagnosis by adding objective and unbiased criteria to the subjective assessment of CFS.
Assuntos
Capnografia/métodos , Síndrome de Fadiga Crônica/diagnóstico , Teste da Mesa Inclinada/métodos , Adulto , Pressão Sanguínea/fisiologia , Testes Respiratórios , Dióxido de Carbono/análise , Síndrome de Fadiga Crônica/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hiperventilação/diagnóstico , Hiperventilação/fisiopatologia , Masculino , Respiração , Volume de Ventilação Pulmonar/fisiologiaRESUMO
OBJECTIVES: To evaluate the cardiovascular response to postural challenge in patients with chronic fatigue syndrome (CFS) and to determine whether the degree of instability of the cardiovascular response may aid in diagnosing CFS. METHODS: Patients with CFS (n = 25) and their age- and gender-matched healthy controls (n = 37), patients with fibromyalgia (n = 30), generalized anxiety disorder (n = 15), and essential hypertension (n = 20) were evaluated with the aid of a standardized tilt test. The blood pressure (BP) and heart rate (HR) were recorded during 10 minutes of recumbence and 30 minutes of head-up tilt. We designated BP changes as the differences between successive BP values and the last recumbent BP. The average and standard deviation (SD) were calculated. Time curves of BP differences were loaded into a computerized image analyzer, and their outline ratios and fractal dimensions were measured. HR changes were determined similarly. The average and SD of the parameters were calculated, and intergroup comparisons were performed. RESULTS: On multivariate analysis, the independent predictors of CFS patients versus healthy controls were the fractal dimension of absolute values of the systolic BP changes (SYST-FD.abs), the standard deviation of the current values of the systolic BP changes (SYST-SD.cur), and the standard deviation of the current values of the heart rate changes (HR-SD.cur). The following equation was deduced to calculate the hemodynamic instability score (HIS) in the individual patient: HIS = 64.3303 + (SYST-FD.abs x -68.0135) + (SYST-SD.cur x 111.3726) + (HR-SD.cur x 60.4164). The best cutoff differentiating CFS from the healthy controls was -0.98. HIS values >-0.98 were associated with CFS (sensitivity 97%, specificity 97%). The HIS differed significantly between CFS and other groups (P <.0001) except for generalized anxiety disorder. Group averages (SD) of HIS were CFS = +3.72 (5.02), healthy = -4.62 (2.26), fibromyalgia = -3.27 (2.63), hypertension = -5.53 (2.24), and generalized anxiety disorder = +1.08 (5.2). CONCLUSION: The HIS adds objective criteria confirming the diagnosis of CFS.
Assuntos
Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/fisiopatologia , Teste da Mesa Inclinada , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/fisiopatologia , Pressão Sanguínea/fisiologia , Diagnóstico Diferencial , Feminino , Fibromialgia/diagnóstico , Fibromialgia/fisiopatologia , Fractais , Frequência Cardíaca/fisiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Processamento de Imagem Assistida por Computador , MasculinoRESUMO
Microvillous inclusion disease (MID) is characterized by diffuse villous atrophy without inflammatory changes. While increased apoptosis has been related to mucosal flattening in celiac disease, the role of apoptosis in the pathogenesis of MID is unknown. The aim of this study was to assess the rates of apoptosis and cell proliferation in MID and to compare them with those of normal controls and celiac disease. Small intestinal biopsies from 5 infants with MID, 10 children with normal villous architecture, and 10 children with untreated celiac disease were stained with the terminal uridine deoxynucleotidyl nick end labeling (TUNEL) method to assess apoptotic activity, and with Ki-67 immunohistochemistry to assess cellular proliferation. TUNEL and Ki-67 positive enterocytes were counted in a minimum of 20 well oriented half crypts per section. The percentage of apoptotic cells per crypt (apoptotic index) in normal, MID, and celiac biopsies was 0.03 +/- 0.01%, 0.08 +/- 0.08%, and 0.16 +/- 0.3%, respectively. Significant differences were found between normal and MID, and between normal and celiac cases. The percentage of Ki-67 positive cells per crypt (proliferation index) in normal, MID, and celiac cases was 14 +/- 2.5%, 28 +/- 9.2%, and 56 +/- 14%. Significant differences were found between the 3 groups. In conclusion, (1) enterocyte apoptosis and proliferation are increased in MID; (2) apoptosis appears to be an important factor of cell loss and may be, at least in part, responsible for villous atrophy in MID; and (3) crypts in MID are hyperplastic and not hypoplastic. HUM PATHOL 31:1404-1410.
Assuntos
Apoptose , Diarreia Infantil/patologia , Enterócitos/patologia , Intestino Delgado/patologia , Microvilosidades/patologia , Atrofia , DNA/análise , Diarreia Infantil/genética , Diarreia Infantil/metabolismo , Enterócitos/metabolismo , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Lactente , Recém-Nascido , Intestino Delgado/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Microvilosidades/metabolismo , Índice MitóticoRESUMO
PURPOSE: The aim of this work was to detect nuclear parameters related to the prognosis of patients with stage III, IV or DS neuroblastomas. METHODS: Histological sections of 25 operation specimens obtained from children with advanced-stage neuroblastomas were subjected to computer-assisted image analysis. Statistical relationships between nuclear descriptors of the tumor cells and patients' clinical outcome were determined. RESULTS: The coefficient of variability of the mean nuclear area the mean nuclear elongation factor, and the mean nuclear averaged Feret diameter of the neuroblastoma cells were ascertained to be discriminators separating high-grade from low-grade tumors. CONCLUSIONS: The histomorphometrically gauged nuclear parameters may help oncologists to assess the prognosis of patients with advanced-stage neuroblastoma.
Assuntos
Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Processamento de Imagem Assistida por Computador/normas , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Fatores Etários , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Modelos Logísticos , Masculino , Neoplasias do Mediastino/mortalidade , Neoplasias do Mediastino/patologia , Neoplasias Pélvicas/mortalidade , Neoplasias Pélvicas/patologia , Valor Preditivo dos Testes , Prognóstico , Neoplasias Retroperitoneais/mortalidade , Neoplasias Retroperitoneais/patologia , Análise de SobrevidaRESUMO
The capillary basement membranes from 16 skeletal muscle biopsies from patients with a clinical and histological diagnosis of inflammatory myopathy and from six controls were analysed ultrastructurally and morphometrically. Resin sections from 244 endomysial capillaries were examined by light microscope, and the results were correlated with findings seen in electron micrographs of these capillaries. The ultrastructural morphometric measurements and the statistical analysis showed that the capillary basement membrane was thick and multilaminated in 87% specimens affected by inflammatory myopathy. No thick or multilaminated basement membrane was observed in controls. In inflammatory myopathy the endomysial space next to the capillaries contained an increased amount of collagen fibrils and showed signs of a chronic reparative process. It is suggested that the thick multilaminated basement membrane in inflammatory myopathy represents an advanced stage of vascular regeneration.
Assuntos
Membrana Basal/ultraestrutura , Capilares/ultraestrutura , Músculo Esquelético/ultraestrutura , Polimiosite/patologia , Adolescente , Adulto , Criança , Dermatomiosite/patologia , Endotélio Vascular/ultraestrutura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Pericitos/ultraestruturaRESUMO
We investigated the role of tumour necrosis factor-alpha (TNF) in the evaluation of pleural effusion aetiology. Using a commercially-available ELISA kit, concentrations of TNF were measured in the serum and pleural fluid of patients with malignant effusions (n=19), uncomplicated parapneumonic effusions (n=13), and exudative (n=13) and transudative (n=13) effusions due to congestive heart failure (CHFex and CHFtr, respectively). Serum TNF did not differ significantly between the four groups (p>0.05). In the group with malignancy, pleural fluid TNF was significantly higher than in the other groups (p<0.001), which were not significant different from each other (p>0.05). However, a considerable overlap between all four groups was found. Pleural fluid TNF was significantly higher than serum TNF in the malignant and the uncomplicated parapneumonic groups (p<0.001), and there was a significant positive correlation between serum TNF and pleural fluid TNF in the group with uncomplicated parapneumonic effusion (r=0.7, p<0.005), in the group with CHFex (r=0.54, p<0.01), and in the group with CHFtr (r=0. 8, p<0.005), but not in the group with malignancy. Pleural fluid TNF:serum TNF (TNF ratio) was significantly higher in the malignancy group than in the other groups (p<0.001); no significant difference was found between the other three groups (p>0.05). At an optimal cut-off point of 2.0 for TNF ratio, determined by ROC analysis for discrimination between malignant and non-malignant groups, sensitivity was 84%, specificity 90%, and total accuracy 88% (p<0. 0001). TNF ratio might be helpful in the diagnostic assessment of exudative pleural effusion.
Assuntos
Derrame Pleural/diagnóstico , Fator de Necrose Tumoral alfa/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/química , Derrame Pleural/etiologia , Derrame Pleural Maligno/diagnóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Aberrations of cardiovascular reactivity (CVR), an expression of autonomic function, occur in a number of clinical conditions, but lack specificity for a particular disorder. Recently, a CVR pattern particular to chronic fatigue syndrome was observed. AIM: To assess whether specific CVR patterns can be described for other clinical conditions. METHODS: Six groups of patients, matched for age and gender, were evaluated with a shortened head-up tilt test: patients with chronic fatigue syndrome (CFS) (n = 20), non-CFS fatigue (F) (n = 15), neurally-mediated syncope (SY) (n = 21), familial Mediterranean fever (FMF) (n = 17), psoriatic arthritis (PSOR) (n = 19) and healthy subjects (H) (n = 20). A 10-min supine phase was followed by recording 600 cardiac cycles on tilt (5-10 min). Beat-to-beat heart rate (HR) and pulse transit time (PTT) were measured. Results were analysed using conventional statistics, recurrence plot analysis and fractal analysis. RESULTS: Multivariate analysis evaluated independent predictors of the CVR in each patient group vs. all other groups. Based on these predictors, equations were determined for a linear discriminant score (DS) for each group. The best sensitivities and specificities of the DS, consistent with disease-related phenotypes of CVR, were noted in the following groups: CFS, 90.0% and 60%; SY, 93.3% and 62.5%; FMF, 90.1% and 75.4%, respectively. DISCUSSION: Pathological disturbances may alter cardiovascular reactivity. Our data support the existence of disease-related CVR phenotypes, with implications for pathogenesis and differential diagnosis.