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1.
J Forensic Leg Med ; 17(6): 293-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20650415

RESUMO

The purpose of the study was to determine whether Infrared imaging could play a role in the detection of previous blunt force injury after resolution of skin changes were no longer visible to the human eye. Investigations were performed using an adapted digital camera and the same standard Nikon camera body to photograph the bruises of ten volunteer adult subjects. The same lens was fitted to each camera body and each bruise was photographed until it was no longer possible to identify it with the naked eye. The results of photographing subjects over 6 months demonstrated that the median time the bruises persisted in both groups was approximately between 18 and 19 days. There was no statistically significant difference between groups of bruises photographed with both the infrared digital camera that had been adapted to capture only infrared light, and with the standard camera which had the same lens fitted to it. The two groups of photographs of bruises imaged at the same time with the two cameras were not significantly different with regard to what skin changes could be detected. The use of the near infrared spectrum, with wavelengths that are longer than the human eye can detect, did not reveal significant evidence of bruising after it had faded from view to both the human eye and to a standard camera.


Assuntos
Contusões/diagnóstico , Medicina Legal/instrumentação , Raios Infravermelhos , Fotografação/instrumentação , Exame Físico/instrumentação , Identificação Biométrica , Intervalos de Confiança , Estudos de Viabilidade , Medicina Legal/métodos , Medicina Legal/tendências , Humanos , Estimativa de Kaplan-Meier , Fotografação/métodos , Exame Físico/métodos , Estatísticas não Paramétricas
2.
J Clin Pathol ; 57(2): 208-9, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14747454

RESUMO

Waterhouse-Friderichsen syndrome--massive adrenal haemorrhage in the setting of overwhelming clinical sepsis--is usually taken at necropsy to indicate meningococcal infection, and may be the only evidence of this pathogen. This report describes three fatal cases of the syndrome in which the causative organism proved to be a streptococcus. The organisms were detected during routine coroners' autopsies with histology and microbiological investigations. In two cases, the syndrome followed Streptococcus pneumoniae infection and in a third beta haemolytic streptococcus group A. Thus, adrenal haemorrhage alone cannot be taken to indicate meningococcal disease and other pathogens, particularly streptococcus, must be considered.


Assuntos
Infecções Estreptocócicas/diagnóstico , Síndrome de Waterhouse-Friderichsen/diagnóstico , Doenças das Glândulas Suprarrenais/diagnóstico , Doenças das Glândulas Suprarrenais/microbiologia , Idoso , Pré-Escolar , Evolução Fatal , Hemorragia/diagnóstico , Hemorragia/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pyogenes/isolamento & purificação , Síndrome de Waterhouse-Friderichsen/microbiologia
3.
J Physiol ; 538(Pt 2): 541-53, 2002 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11790818

RESUMO

A non-invasive cine magnetic resonance imaging (MRI) technique was developed to allow, for the first time, detection and characterization of chronic changes in myocardial tissue volume and the effects upon these of treatment by the angiotensin-converting enzyme (ACE) inhibitor captopril in streptozotocin (STZ)-diabetic male Wistar rats. Animals that had been made diabetic at the ages of 7, 10 and 13 weeks and a captopril-treated group of animals made diabetic at the age of 7 weeks were scanned. The findings were compared with the results from age-matched controls. All animal groups (n = 4 animals in each) were consistently scanned at 16 weeks. Left and right ventricular myocardial volumes were reconstructed from complete data sets of left and right ventricular transverse sections which covered systole and most of diastole using twelve equally incremented time points through the cardiac cycle. The calculated volumes remained consistent through all twelve time points of the cardiac cycle in all five experimental groups and agreed with the corresponding post-mortem determinations. These gave consistent myocardial densities whose values could additionally be corroborated by previous reports, confirming the validity of the quantitative MRI results and analysis. The myocardial volumes were conserved in animals whose diabetes was induced at 13 weeks but were significantly increased relative to body weight in animals made diabetic at 7 and 10 weeks. Captopril treatment, which was started immediately after induction of diabetes, prevented the development of this relative hypertrophy in both the left and right ventricles. We have thus introduced and validated quantitative MRI methods in a demonstration, for the first time, of chronic myocardial changes in both the right and left ventricles of STZ-diabetic rats and their prevention by the ACE inhibitor captopril.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Diabetes Mellitus Experimental/patologia , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Animais , Diabetes Mellitus Experimental/fisiopatologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Hipertrofia Ventricular Direita/prevenção & controle , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar
4.
J Physiol ; 538(Pt 2): 555-72, 2002 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11790819

RESUMO

Non-invasive magnetic resonance imaging (MRI) was used to characterize changes in left and right ventricular cardiac cycles following induction of experimental, streptozotocin (STZ)-induced, diabetes in male Wistar rats at different ages. The effects of the angiotensin-converting enzyme (ACE) inhibitor captopril upon such chronic physiological changes were then evaluated, also for the first time. Diabetes was induced at the age of 7 weeks in two experimental groups, of which one group was subsequently maintained on captopril (2 g l(-1))-containing drinking water, and at 10 and 13 weeks in two further groups. The fifth group provided age-matched controls. All groups (each n = 4 animals) were scanned consistently at 16 weeks, in parallel with timings used in earlier studies that employed this experimental model. Cine magnetic resonance (MR) image acquisition provided transverse sections through both ventricles at twelve time points covering systole and most of diastole. These yielded reconstructions of cardiac anatomy used to derive critical functional indices and their dependence upon time following the triggering electrocardiographic R waves. The left and right ventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes (SV), and ejection fractions (EF) calculated from each, control and experimental, group showed matching values. This confirmed a necessary condition requiring balanced right and left ventricular outputs and further suggested that STZ-induced diabetes produced physiological changes in both ventricles. Absolute left and right ventricular SVs were significantly altered in all diabetic animals; EDVs and EFs significantly altered in animals diabetic from 7 and 10 but not 13 weeks. When normalized to body weight, left and right ventricular SVs had significantly altered in animals diabetic from 7 and 10 weeks but not 13 weeks. Normalized left ventricular EDVs were also significantly altered in animals diabetic from 7 and 10 weeks. However, normalized right ventricular EDVs were significantly altered only in animals made diabetic from 7 weeks. Diabetic hearts showed major kinetic changes in left and right ventricular contraction (ejection) and relaxation (filling). Both the initial rates of volume change (dV/dt) in both ventricles and the plots of dV/dt values through the cardiac cycle demonstrated more gradual developments of tension during systole and relaxation during diastole. Estimates of the derived left ventricular performance parameters of cardiac output, cardiac power output and stroke work in control animals were comparable with human values when normalized to both body (or cardiac) weight and heart rate. All deteriorated with diabetes. Comparisons of experimental groups diabetic from 7 weeks demonstrated that captopril treatment relieved the alterations in critical volumes, dependence of SV upon EDV, kinetics of systolic contraction and diastolic relaxation and in the derived indicators of ventricular performance. This study represents the first demonstration using non-invasive MRI of early, chronic changes in diastolic filling and systolic ejection in both the left and the right ventricles and of their amelioration by ACE inhibition following STZ-induction of diabetes in intact experimental animals.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Imagem Cinética por Ressonância Magnética , Animais , Circulação Coronária , Diabetes Mellitus Experimental/diagnóstico , Masculino , Contração Miocárdica , Ratos , Ratos Wistar , Volume Sistólico , Função Ventricular Esquerda/efeitos dos fármacos
5.
J Physiol ; 513 ( Pt 3): 873-87, 1998 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9824724

RESUMO

1. We have used magnetic resonance imaging (MRI) to examine acute morphological changes in the left ventricle throughout the cardiac cycle in normal Wistar Kyoto rats (WKY) and also to follow the development of chronic changes in spontaneously hypertensive rats (SHR). This involved the development of MRI and quantitative analysis techniques for characterizing contractile changes during the cardiac cycle. 2. Images of the cardiac anatomy in two age groups (8 and 12 weeks old) of young anaesthetized adult normal WKY and SHR were acquired in planes both parallel and perpendicular to the principal cardiac axis. 3. Complete coverage of the heart by imaging planes was achieved with high time resolution (13 ms), with typically 12 time frames in the cardiac cycle, using a short echo time (5 ms) multislice gradient-echo imaging sequence. Imaging was synchronized to the R wave of the electrocardiogram. 4. The image slices could be reconstructed into complete geometrically and temporally coherent three-dimensional data sets. Left ventricular (LV) volumes were thus reconstructed throughout the cardiac cycle by combining transverse cardiac image sections. This volume analysis revealed structural and functional differences between the normal WKY and SHR in both age groups of 8 and 12 weeks. Measurements from the cardiac images were additionally validated against histological measurements. 5. The SHR showed a raised LV end-systolic volume and a correspondingly poorer ejection fraction as well as LV hypertrophy when compared with the controls. Left ventricular function in the SHR appeared stable between the two age groups. 6. We developed a simple geometrical model of the left ventricle based on a single longitudinal image section and successfully used this to describe some functional parameters of the left ventricle in the WKY and SHR. This geometrical model has the potential to greatly reduce the imaging time needed to study the beating heart in future serial investigations of cardiac physiology in rats. 7. Our experimental and analytical methods together form a powerful set of quantitative techniques which combine both imaging and functional analysis and will be applicable for future studies of chronic physiological changes in animal disease models.


Assuntos
Coração/anatomia & histologia , Hipertensão/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Função Ventricular Esquerda/fisiologia , Animais , Eletrocardiografia , Coração/fisiopatologia , Ventrículos do Coração/anatomia & histologia , Ventrículos do Coração/fisiopatologia , Hemodinâmica/fisiologia , Hipertensão/genética , Processamento de Imagem Assistida por Computador , Masculino , Modelos Biológicos , Contração Miocárdica/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Volume Sistólico/fisiologia
6.
J Clin Pathol ; 50(8): 691-4, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9301556

RESUMO

AIMS: To establish criteria for the information to be included in a necropsy report, and to improve the quality of necropsy reporting in the Anglia Region. METHODS: Discussion between Anglia histopathologists, based on the guidelines of the Royal College of Pathologists, led to a consensus about the ideal content of a necropsy report. Fifteen consecutive necropsies subsequently undertaken by each consultant were assessed against agreed standards. Reaudit was undertaken nearly two years later, without prior announcement. RESULTS: The initial standards achieved for demographic details (70%), history (87%), external examination (43-97%), internal examination (76-95%), organ weights (73%), cause of death in OPCS format (94%), and conclusion (90%) were discussed by the group. Changes to necropsy reporting documentation were proposed. Reaudit showed improvement in nearly all categories. CONCLUSIONS: Necropsy reporting in East Anglia is currently carried out to a reasonably high standard, and improvements have occurred as a result of the audit. There was no evidence that reports on coroners' necropsies were of a lower standard than those done for the hospital. Improvement in the format of the documentation increases the likelihood that all relevant and important data are recorded.


Assuntos
Autopsia/normas , Auditoria Médica , Médicos Legistas , Inglaterra , Hospitais , Humanos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
7.
J Clin Pathol ; 50(8): 695-8, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9301557

RESUMO

AIM: To examine current practice and to establish criteria for the use of histopathology in necropsy practice. METHODS: During an audit of necropsy reporting, consensus could not be reached about the use of routine histopathology. Therefore local guidelines were formulated and current practice was compared with these guidelines. Fifteen consecutive necropsies undertaken by each consultant were reviewed and the use of histopathology noted. RESULTS: In general, the standard of necropsy reporting was reasonably high. Tissue was retained for histopathology in 25% of necropsies and 72% of these necropsy reports included a histopathology report. Using the guidelines, the assessors judged that histopathology might have been valuable in a further 19%. It was felt that routine histopathology would not have been helpful in determining the cause of death in the remaining 56%. The importance of the pathologist's clinical judgement in individual cases was stressed. At reaudit, nearly two years later, there was no significant change in practice, reflecting the lack of consensus. CONCLUSIONS: Even when histopathology might contribute to finding the cause of death, it was not always done. However, the assumption that histology is invariably helpful in determining the cause of death is challenged.


Assuntos
Autopsia/métodos , Patologia/organização & administração , Guias de Prática Clínica como Assunto , Prática Profissional , Médicos Legistas , Inglaterra , Hospitais , Humanos , Auditoria Médica , Preservação de Tecido
8.
Arch Pathol Lab Med ; 121(12): 1269-71, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9431317

RESUMO

OBJECTIVE: To show lipid deposits in the lung of patients treated with amiodarone. MATERIALS AND METHODS: Formalin-fixed, unstained frozen sections were used to reveal lipid deposits by means of polarized light. Lung tissues obtained at the postmortem examination of one patient and the surgical biopsy of another were available. RESULTS: Birefringent lipid deposits were seen in the alveolar lining cells and macrophages, as well as in the walls of arterioles and venules. CONCLUSIONS: To assess the effect of amiodarone on the lung, polarized light microscopy of unstained, frozen sections is a simple and rapid method.


Assuntos
Amiodarona/farmacologia , Antiarrítmicos/farmacologia , Pulmão/efeitos dos fármacos , Arteríolas/química , Relação Dose-Resposta a Droga , Endotélio Vascular/química , Secções Congeladas , Humanos , Lipídeos/análise , Pulmão/irrigação sanguínea , Pulmão/química , Pulmão/citologia , Macrófagos Alveolares/química , Macrófagos Alveolares/citologia , Masculino , Microscopia de Polarização/métodos , Pessoa de Meia-Idade , Fosfolipases/antagonistas & inibidores , Fósforo/análise , Alvéolos Pulmonares/química , Alvéolos Pulmonares/citologia , Surfactantes Pulmonares/análise , Vênulas/química
9.
Invest Radiol ; 31(10): 630-8, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8889652

RESUMO

RATIONALE AND OBJECTIVES: The authors develop a scoring system for assessing those features of degeneration of the STR/ORT mouse knee visualizable by magnetic resonance (MR) imaging, and to validate those MR scores by comparison with x-ray and histology. METHOD: Magnetic resonance imaging, histology, and x-ray have been used in a cross-sectional study to visualize the anatomy and pathology of the knees of three pairs of male STR/ORT mice and their approximately age-matched female pairs. A scoring system was developed that distinguished the faster rate of damage of the males from the slower progressive changes seen in the females. RESULTS: Changes in the patellar tendon were observed in MR imaging of the 5-month-old male knee. Sagittal images showed other degenerative features such as sclerosis and loss of signal from synovial fluid after 9 months; osteophytes and degeneration of the tibial plateau were better visualized in the coronal plane. Cysts were poorly correlated to the progression of the disease. Similar trends were observed for four features scored in x-rays (sclerosis, joint space narrowing, cysts, and osteophytes) and cartilage degradation assessed using histology. In contrast, the age-matched females were less affected. CONCLUSIONS: Magnetic resonance imaging can identify joint degeneration in the knees of male mice, which develops more rapidly than in age-matched females. Those observations were validated by radiology and histology.


Assuntos
Articulação do Joelho/patologia , Imageamento por Ressonância Magnética , Osteoartrite/diagnóstico , Animais , Feminino , Membro Posterior , Articulação do Joelho/diagnóstico por imagem , Masculino , Camundongos , Camundongos Endogâmicos , Radiografia , Fatores Sexuais
10.
Br J Pharmacol ; 118(7): 1584-91, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8842418

RESUMO

1. Subcutaneous implantation of sterile polyether sponges elicited a reproducible neovascular response in rats, as determined by blood flow measurement with a 133Xe clearance technique and confirmed histologically. This model was used to monitor the levels of two cytokines during angiogenesis and to compare the activities of angiostatic steroids and anti-inflammatory steroids. 2. Initial experiments followed the neovascular development over a 20-day period. Daily local injection of hydrocortisone caused a dose-dependent (0.5, 5 and 50 micrograms per sponge) inhibition of the basal sponge-induced angiogenesis. However, daily systemic treatment of hydrocortisone (2, 10 and 50 mg kg-1, s.c.) was less effective at inhibiting angiogenesis, and this inhibition was not sustained by day 20 after sponge implantation. 3. To investigate the involvement of cytokines during the course of angiogenesis, we measured the endogenous levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in sponge implants. Levels of IL-6 and TNF-alpha peaked at day 7 and day 11 after implantation, respectively. These cytokine levels subsided through the completion of angiogenesis by day 20. 4. Subsequent experiments were carried out over a 14-day period. Among the three angiostatic steroids tested, U-24067 (6 alpha-fluoro-17,21 - dihydroxy-16 alpha-methylpregna -4,9(11)-diene-3,20-dione-21-acetate) showed a dose-dependent inhibition (0.5, 5 and 50 micrograms per sponge per day) of sponge-induced angiogenesis. Tetrahydro-S was also effective at 5 micrograms doses, but medroxyprogesterone failed to affect the angiogenic response. None of these steroids caused atrophies of the spleen and thymus. 5. Daily local injection of dexamethasone (0.5 microgram per sponge) inhibited the basal sponge-induced angiogenesis almost completely. Although higher doses of dexamethasone (5 and 50 micrograms per sponge) did not produce further inhibition of angiogenesis, they caused severe spleen and thymus weight losses, indicative of immunosuppression. 6. At the daily dose of 5 micrograms per sponge, dexamethasone inhibited angiogenesis and produced a marked reduction in the levels of TNF-alpha and IL-6 at day 14. In contrast, hydrocortisone, U-24067 and tetrahydro-S did not influence the levels of TNF-alpha and IL-6. 7. We concluded that the anti-angiogenic activity of angiostatic steroids and anti-inflammatory steroids in the rat sponge model is independent of their ability to reduce the production of TNF-alpha and IL-6. The differential effects of angiostatic and anti-inflammatory steroids suggest that U-24067 and its derivatives may have therapeutic potential in the management of angiogenic diseases such as rheumatoid arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Neovascularização Patológica/fisiopatologia , Animais , Linhagem Celular , Hidrocortisona/farmacologia , Inflamação/induzido quimicamente , Interleucina-6/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Radioisótopos de Xenônio
11.
Lab Anim Sci ; 45(6): 674-9, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8746529

RESUMO

Details in the living animal can be compared with respective histologic section taken after death. In less than 35 min, 12 to 16 coronal and transverse images through the brain can be obtained, each with an in-plane resolution of 100 x 200 microns and a slice thickness of 900 microns. The experimental parameters can be manipulated not only to achieve different tissue contrast but also to access any desired plane.


Assuntos
Encéfalo/citologia , Imageamento por Ressonância Magnética , Animais , Cerebelo/citologia , Técnicas Histológicas , Camundongos , Condutos Olfatórios/citologia , Prosencéfalo/citologia , Valores de Referência
12.
Lab Invest ; 72(5): 601-10, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7538184

RESUMO

BACKGROUND: We have previously described a method of quantitating angiogenesis by using a simple 133Xe clearance technique for repeated measurement of relative blood flow changes through s.c. sponge implants over a period of 14 days. The quantitative requirement of this bioassay is that the measurements of 6-minute 133Xe clearance should provide a fast and reliable means to detect relative blood flow changes in the neovasculature, so a more vigorous validation of the use of the 133Xe clearance technique as an indicator of angiogenesis is needed. EXPERIMENTAL DESIGN: Four different techniques were used: (a) to measure absolute blood flow in the sponges using 113Sn microspheres; (b) to quantitate the levels of hemoglobin and total protein in the implants; (c) to determine the amount of neovasculature in the sponges by the carmine dye method; and (d) to carry out histologic and morphometric analysis of sponge implants. To confirm parallel changes in 133Xe clearance and in the other techniques, the effects of selected angiogenic promoters and inhibitors were also investigated. RESULTS: There was a good correlation between 133Xe clearance from the sponges and absolute blood flow (r = 0.952, p < 0.01); the levels of hemoglobin (r = 0.982, p < 0.01) and total protein (r = 0.962, p < 0.01); the amount of carmine dye (r = 0.974, p < 0.01); the fibrovascular growth areas (r = 0.992, p < 0.01); and the vascular density (r = 0.997, p < 0.01) in the implants. Daily administration of 3 pmol of IL-1 alpha or IL-8 caused intense neovascularization. When given alone, lower doses of IL-1 alpha (0.3 pmol) or bradykinin (10 pmol) produced no apparent effect. However, co-administration of these doses to a single sponge together caused an increase in the rate of angiogenesis similar to that seen with a higher dose of IL-1 alpha (3 pmol) acting alone. In contrast, daily co-administration of a potent and selective protein kinase C inhibitor, calphostin C (4 micrograms), inhibited the neovascular response elicited by 3 pmol of IL-1 alpha. Furthermore, daily doses of 5 micrograms of dexamethasone for 14 days inhibited sponge-induced angiogenesis. CONCLUSIONS: The results clearly show that the 133Xe clearance technique not only gives an indication of the rate of perfusion of the sponges with blood but also gives a good estimate of its functional vascularity. Thus, the measurement of 133Xe clearance in the sponge implant provides a simple and objective method for routine studies of modifiers of angiogenesis.


Assuntos
Naftalenos , Neovascularização Patológica/fisiopatologia , Animais , Dexametasona/farmacologia , Interleucina-1/fisiologia , Interleucina-8/fisiologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Compostos Policíclicos/farmacologia , Próteses e Implantes , Ratos , Fluxo Sanguíneo Regional/fisiologia , Tampões de Gaze Cirúrgicos , Radioisótopos de Xenônio
13.
Inflammation ; 18(1): 45-58, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7515856

RESUMO

Daily administration of 50 ng recombinant human interleukin 1-alpha (IL-1 alpha), 25 ng IL-8, 50 ng tumor necrosis factor-alpha (TNF-alpha), or 100 ng basic fibroblast growth factor (bFGF) caused intense neovascularization in a rat sponge model. These cytokine-induced neovascular responses were inhibited by coadministration of IL-1 receptor antagonist (IL-1ra; 50 micrograms), IL-8 antiserum (IL-8-AS; 1: 1000), TNF-alpha antibody (TNF-AB; 500 ng), or a monoclonal antibody to bFGF (DG2; 1000 ng), respectively. These data suggest that it is possible to manipulate the angiogenic response elicited by a defined cytokine by its receptor antagonist or neutralizing antibody. In the absence of exogenous cytokines, the sponge-induced angiogenesis was profoundly suppressed by dexamethasone (5 micrograms/day), but not modified by IL-1ra, IL-8-AS, TNF-AB, and DG2 alone. However, the combination of these four reagents was able to inhibit the sponge-induced neovascular response almost completely. These findings provide direct evidence that IL-1 alpha, IL-8, TNF-alpha and/or bFGF have an intrinsic role in angiogenesis. Further work is necessary to characterize the profile of these cytokines during angiogenesis and to elucidate the nature of their interactions.


Assuntos
Anticorpos/imunologia , Citocinas/antagonistas & inibidores , Neovascularização Patológica/prevenção & controle , Receptores de Interleucina-1/antagonistas & inibidores , Animais , Citocinas/imunologia , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Fator 2 de Crescimento de Fibroblastos/imunologia , Humanos , Interleucina-1/antagonistas & inibidores , Interleucina-8/antagonistas & inibidores , Interleucina-8/imunologia , Masculino , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Ratos , Ratos Wistar , Receptores de Interleucina-1/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
14.
Ann Rheum Dis ; 53(1): 30-4, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8311552

RESUMO

OBJECTIVES: Rotator cuff tendinitis and lateral epicondylitis are common in clinical practice but the underlying pathology is poorly understood. The study examined both normal and biopsy tendon specimens histologically, to determine the mechanisms involved in tendon degeneration. METHODS: Rotator cuff tendons from 83 cadavers aged 11-94 and tendon biopsy specimens from 20 patients with lateral epicondylitis aged 27-56 years were examined histologically. RESULTS: The microscopic changes found in the tendon biopsies from the elbow were similar to those found in the cadaveric rotator cuff tendons. Abnormalities ranged from minor blood vessel wall changes and loss of tenocytes to calcification. The most frequent abnormality was glycosaminoglycan infiltration and fibrocartilaginous transformation. There appeared to be some sequence in the changes observed which were milder in younger patients. Only 17% of cadaver tendons, below the age of 39 were abnormal but abnormalities increase in later life to around 40-50%. CONCLUSIONS: There was an increasing incidence of degenerative changes in tendons with age. The changes observed in biopsy samples of common extensor tendons were the same as those seen in aged supraspinatus tendons, but these changes were not seen in control common extensor tendons.


Assuntos
Envelhecimento/patologia , Manguito Rotador/patologia , Cotovelo de Tenista/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Calcinose , Criança , Colágeno/metabolismo , Feminino , Glicosaminoglicanos/metabolismo , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Manguito Rotador/irrigação sanguínea , Manguito Rotador/metabolismo , Cotovelo de Tenista/metabolismo
15.
Br J Pharmacol ; 110(1): 43-9, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7693287

RESUMO

1. Daily administration of 1 nmol substance P or 3 pmol recombinant human interleukin-1 alpha (IL-1 alpha) caused intense neovascularization in a rat sponge model of angiogenesis. Lower doses of substance P (10 pmol) or IL-1 alpha (0.3 pmol) were ineffective when given alone. When combined at these low doses, substances P and IL-1 alpha interacted to produce an enhanced neovascular response. 2. By use of selective tachykinin NK1, NK2 and NK3 receptor agonists, ([Sar9,Met(O2)11]substance P, [beta-Ala8]neurokinin A(4-10), Succ-[Asp6,MePhe8]substance P(6-11) (senktide), respectively), it was established that the activation of NK1 receptors is most likely to mediate the angiogenic response to substance P in this model. 3. The angiogenic activity of substance P and IL-1 alpha (10 pmol and 0.3 pmol day-1, respectively) was abolished by co-administration of (i) the selective peptide NK1 receptor antagonist, L-668,169 (1 nmol day-1), (ii) the selective non-peptide NK1 receptor antagonists, RP 67580 and (+/-)-CP-96,345 (both at 1 nmol day-1) or (iii) the IL-1 receptor antagonist, IL-1ra, (50 micrograms day-1). In contrast, the selective NK2 receptor antagonist, L-659,874 (1 nmol day-1) was ineffective. 4. The angiogenic action of substance P and IL-1 alpha was resistant to modification by mepyramine (1 nmol day-1) and/or cimetidine (10 nmol day-1), indomethacin (7 nmol day-1) or the platelet-activating factor (PAF) antagonist, WEB-2086 (22 nmol day-1), indicating that histamine, prostaglandins and PAF are not likely to be involved in this neovascular response. 5. The inhibition of the substance P/IL-1 angiogenic response by selective NK1 receptor antagonists or by an IL-1 receptor antagonist demonstrates that angiosuppression can be achieved by blocking the activity of angiogenic factors at the receptor level.


Assuntos
Interleucina-1/farmacologia , Neovascularização Patológica/patologia , Antagonistas dos Receptores de Neurocinina-1 , Receptores de Interleucina-1/antagonistas & inibidores , Substância P/farmacologia , 6-Cetoprostaglandina F1 alfa/metabolismo , Animais , Histamina/fisiologia , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Indometacina/farmacologia , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Fator de Ativação de Plaquetas/antagonistas & inibidores , Fator de Ativação de Plaquetas/fisiologia , Prostaglandinas/fisiologia , Ratos , Ratos Wistar , Receptores de Interleucina-1/fisiologia , Receptores da Neurocinina-1/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Radioisótopos de Xenônio
16.
J Clin Pathol ; 46(7): 603-6, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8157743

RESUMO

AIMS: To examine veins histologically from different sites in the body to study the effect of venous pressure; and to examine veins used as aortocoronary grafts. METHODS: The axillary vein, femoral vein at the inguinal ligament, the short saphenous vein at the knee and the long saphenous vein at the ankle were removed from 24 necropsy cases of patients aged 2 months to 80 years. Fifteen varicose saphenous veins and 12 aortocoronary grafts removed at surgery were obtained. All were examined histologically. RESULTS: Varying degrees of intimal thickening composed of collagen, elastin, and smooth muscle were found. These changes were most noticeable in the varicose veins. Intimal changes were also seen related to valves and to adjacent arteries. No clinically relevant lipid was seen in the native veins, though atheromatous changes were seen in the grafts. CONCLUSIONS: Venous changes are related to venous pressure, to local haemodynamic effects, and probably to hypoxia. The changes are often focal and seem to be sequential in their formation. True atheroma is seen in the aortocoronary grafts but is not seen in native veins and this may be the result of additional factors.


Assuntos
Ponte de Artéria Coronária , Veia Safena/patologia , Varizes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Veia Axilar/patologia , Criança , Pré-Escolar , Doença da Artéria Coronariana/patologia , Veia Femoral/patologia , Humanos , Lactente , Pessoa de Meia-Idade , Veia Safena/fisiopatologia , Veia Safena/transplante , Túnica Íntima/patologia , Varizes/fisiopatologia , Pressão Venosa
17.
Circ Res ; 72(3): 526-38, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7679333

RESUMO

The characterization and localization of endothelin A (ETA) and endothelin B (ETB) receptors have been determined in tissue sections of the human atrioventricular conducting system, surrounding regions of atrial and ventricular myocardium, and the left ventricular free wall by use of radioligand binding, polymerase chain reaction, and in situ hybridization. Selective ETA (BQ123) and ETB (BQ3020) compounds in conjunction with [125I]endothelin-1 revealed the presence of ETA and ETB receptors in the left ventricular free wall (BQ123: 57 +/- 5% ETA, 43 +/- 2% ETB, n = 3; BQ3020: 67 +/- 3% ETA, 33 +/- 3% ETB, n = 3). Autoradiography using [125I]endothelin-1 in the absence or presence of BQ3020, BQ123, or endothelin-1 showed ETA and ETB receptors localized to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. There was a higher proportion of ETB receptors in the atrioventricular node and the penetrating and branching bundles of His than in the surrounding interventricular and interatrial septa (p < 0.0001). There was a lower density of ETB receptors in the interventricular septum compared with the interatrial septum and the atrioventricular conducting system (p = 0.009) and a lower density of ETA receptors in the atrioventricular conducting system compared with interatrial and interventricular septa (p = 0.008). Isolated right atrial myocytes showed a higher proportion of ETA receptors (91 +/- 12%, n = 3). Amplification of left ventricular free wall cDNA by polymerase chain reaction revealed the presence of ETA and ETB receptor mRNA. mRNA for both subtypes was detected in isolated atrial myocytes. In situ hybridization showed ETA and ETB receptor mRNA localization to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. These studies demonstrate the presence of ETA and ETB receptors in human myocardium and the atrioventricular conducting system.


Assuntos
Fascículo Atrioventricular/química , Sistema de Condução Cardíaco/química , Miocárdio/química , Receptores de Endotelina/análise , Sequência de Aminoácidos , Sequência de Bases , Endocárdio/química , Endotelinas/farmacologia , Átrios do Coração/química , Ventrículos do Coração , Humanos , Dados de Sequência Molecular , Fragmentos de Peptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , RNA/análise , Receptores de Endotelina/efeitos dos fármacos
19.
Forensic Sci Int ; 50(2): 227-38, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1748358

RESUMO

This work was inspired by a recent case of child abuse where the question of the age of the bruises on the body was raised. The first part of this paper reviews published work on bruises. It illustrates the paucity of work in this field and the absence of studies of the colour changes in bruises of human skin with time. The second part of this paper consists of our own study of the appearance of bruises. The aim was to identify the colour changes which occur in bruises and over what time-scale, in order to determine whether bruises can be aged by appearance. A total of 369 photographs were obtained of bruises aged less than 6 h and up to 21 days old, in 89 subjects aged 10-100 years. It was found that the development of a yellow colour was the most significant change (subjects aged less than 65, P less than 0.001; subjects aged greater than or equal to 65 years, P less than 0.001). The development of a yellow colour occurred significantly faster in subjects aged less than 65 years. (P less than 0.001). The appearance of a blue and purple/black colour was of lesser significance. The appearance of a red colour did not alter significantly with time. From this study it was only possible to conclude that a bruise with a yellow colour was more than 18 h old.


Assuntos
Contusões/patologia , Ferimentos não Penetrantes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Cor , Humanos , Pessoa de Meia-Idade , Fotografação , Fatores de Tempo
20.
BMJ ; 303(6797): 312, 1991 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-1888944
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