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1.
S Afr Med J ; 114(7): e1829, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39041518

RESUMO

BACKGROUND: Traumatic brain injury (TBI) can result in significant morbidity and mortality if not diagnosed in a timely manner. Brain computed tomography (CT) is the diagnostic gold standard but is of limited availability in most South African public hospitals, resulting in transfer of TBI patients to tertiary hospitals. OBJECTIVE: To describe the referral patterns and outcomes of patients with TBI referred to Groote Schuur Hospital Trauma Centre. METHODS: This was a retrospective audit of all patients admitted to the Trauma Centre who had a brain CT scan for suspected TBI between 1 February 2022 and 31 March 2022. Demographic data (age, sex), mechanism of injury and Glasgow Coma Score were recorded. Referral pathways were determined, and final disposition of patients was recorded. RESULTS: A total of 522 patients had a brain CT for TBI. Of these, 314 (60.1%) were referred from other hospitals. CT scan was abnormal in 178 (34.1%) patients. Three hundred and two (58.6%) were discharged home within 24 hours. The mean time between referral and CT scan was 13 hours. CONCLUSION: More than half of patients referred for a CT scan were discharged from the Trauma Centre within 24 hours of admission, which indicates additional costs and inefficiencies in the health system. These data are useful to guide resource planning and allocation for district hospitals, since less expensive point-of-care modalities now exist to diagnose TBI, and which are useful in indicating the prognosis of patients.


Assuntos
Lesões Encefálicas Traumáticas , Encaminhamento e Consulta , Tomografia Computadorizada por Raios X , Centros de Traumatologia , Humanos , Encaminhamento e Consulta/estatística & dados numéricos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/epidemiologia , Masculino , África do Sul/epidemiologia , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Escala de Coma de Glasgow , Adolescente , Adulto Jovem , Idoso
2.
S Afr J Surg ; 60(2): 84-90, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35851360

RESUMO

BACKGROUND: Damage control laparotomy (DCL) is associated with high mortality. The purpose of this study was to review the outcomes of DCL. METHODS: All patients undergoing DCL for penetrating trauma from May 2015 to July 2017 were reviewed. Data retrieved were demographics, mechanism of injury, vitals, and biochemical parameters. Injury severity was described by the revised trauma score (RTS), penetrating abdominal trauma index (PATI), injury severity score (ISS) and trauma and injury severity score (TRISS). Indications for DCL, length of ICU stay, number of procedures and primary abdominal closure rates, complications and mortality were recorded. RESULTS: Fifty-one patients underwent DCL and 47 patients sustained gunshot injuries. Indications for laparotomy were haemodynamic instability (n = 27) and peritonism in stable patients (n = 22). The medians for the different severity scores were RTS 7.36, ISS 20, and PATI 30. The organs most commonly injured, in decreasing frequency, were small bowel (33), large bowel (25), abdominal vasculature (22), liver (18), stomach (14), kidney (10), diaphragm (10), spleen (9) and pancreas (8). DCL procedures performed were abdominal packing (36), temporary bowel ligation (30), vascular (5) and ureteric (1) shunting. The median number of laparotomies performed per patient was three, with a primary fascial closure rate of 69%. The mortality rate was 29%. CONCLUSION: DCL in our centre is associated with a 29% mortality rate. Severe acidosis, massive blood transfusion in first 24 hours and median PATI score more than 47 are independent risk factors associated with increased mortality.


Assuntos
Traumatismos Abdominais , Laparotomia , Traumatismos Abdominais/cirurgia , Humanos , Escala de Gravidade do Ferimento , Laparotomia/efeitos adversos , Centros de Traumatologia , Resultado do Tratamento
3.
Injury ; 52(2): 248-252, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33223253

RESUMO

BACKGROUND: Management of colon injuries has significantly evolved in the recent decades resulting in considerably decreased morbidity and mortality. We set out to investigate penetrating colon injuries in a high-volume urban academic trauma center in South Africa. METHODS: All patients with penetrating colon injuries admitted between 1/2015 and 1/2018 were prospectively enrolled. Data collection included demographics, injury profile and outcomes. Primary outcome was in-hospital mortality. Secondary outcome was morbidity. RESULTS: Two-hundred and five patients were included in the analysis. Stab and gunshot wounds constituted 18% and 82% of the cases, respectively. Mean age was 28.9 (10.2) years and 96.1% were male. Median injury severity score (ISS) and penetrating abdominal trauma index (PATI) were 16 (9-25) and 19 (10-26), respectively. A total of 47.8% of the patients had a complication per Clavien-Dindo classification. Colon leak rate was 2.4%. Wound and abdominal organ/space infection rate was 15.1 and 6.3%, respectively. Overall in-hospital mortality was 9.3%. Risk factors for mortality were higher ISS and PATI, shock on admission, need for blood transfusion, intra-abdominal vascular injury, damage control surgery, and extra-abdominal severe injuries. CONCLUSIONS: Contemporary overall complication rate remains high in penetrating colon injuries, however, anastomotic leak rate is decreasing. Colon injury associated mortality is related to overall injury burden and hemorrhage rather than to colon injuries.


Assuntos
Traumatismos Abdominais , Ferimentos por Arma de Fogo , Ferimentos Penetrantes , Traumatismos Abdominais/epidemiologia , Traumatismos Abdominais/cirurgia , Adulto , Colo/lesões , Colo/cirurgia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Estudos Prospectivos , Estudos Retrospectivos , África do Sul/epidemiologia , Ferimentos por Arma de Fogo/epidemiologia , Ferimentos por Arma de Fogo/cirurgia , Ferimentos Penetrantes/epidemiologia , Ferimentos Penetrantes/cirurgia
4.
Phys Rev Lett ; 118(5): 052501, 2017 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-28211717

RESUMO

Previous experiments observed a 4^{+} state in the N=28 nucleus ^{44}S and suggested that this state may exhibit a hindered E2-decay rate, inconsistent with being a member of the collective ground state band. We populate this state via two-proton knockout from a beam of exotic ^{46}Ar projectiles and measure its lifetime using the recoil distance method with the GRETINA γ-ray spectrometer. The result, 76(14)_{stat}(20)_{syst} ps, implies a hindered transition of B(E2;4^{+}→2_{1}^{+})=0.61(19) single-particle or Weisskopf units strength and supports the interpretation of the 4^{+} state as a K=4 isomer, the first example of a high-K isomer in a nucleus of such low mass.

5.
Drug Deliv ; 23(9): 3594-3605, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27689451

RESUMO

Ultrasound is both a valuable diagnostic tool and a promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles that may also encapsulate and shield therapeutic agents in the bloodstream. Here, the effect of color-Doppler ultrasound exposure on bevacizumab-loaded liposome delivery into the vascular bed was assessed in atheromatous porcine carotids. Bevacizumab, an anti-angiogenic antibody to vascular endothelial growth factor (VEGF-A), was loaded into echogenic liposomes (BEV-ELIP) and confirmed to be immunoreactive. BEV-ELIP flowing within the lumen were exposed to color-Doppler ultrasound at three acoustic pressures for 3.5 min during treatment at physiologic temperature and fluid pressure. To confirm the presence of bubble activity, cavitation was detected within the lumen by a single-element passive cavitation detector. After treatment, the artery was fixed at physiologic pressure and subjected to immunohistochemical analysis to assess the penetration of bevacizumab within the carotid wall. The results suggest that other factors may more strongly influence the deposition of bevacizumab into carotid tissue than color-Doppler ultrasound and cavitation. In both sets of arteries, preferential accumulation of bevacizumab occurred in locations associated with atheroma progression and neointimal thickening: fibrous tissue, necrotic plaque and areas near macrophage infiltration. The delivery of bevacizumab to carotid vascular tissue correlated with the properties of the tissue bed, such as permeability, or affinity for growth-factor binding. Future investigations using this novel therapeutic strategy may focus on characterizing the spatial extent of delivery and bevacizumab colocalization with biochemical markers of atheroma.


Assuntos
Bevacizumab/administração & dosagem , Bevacizumab/química , Lipossomos/química , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/química , Animais , Suínos , Ultrassom/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Anaesthesia ; 69(4): 387-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24641646
7.
J Appl Microbiol ; 115(2): 398-408, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23692445

RESUMO

AIMS: To develop test methods and evaluate survival of Bacillus anthracis Ames, B. anthracis ∆Sterne and B. thuringiensis Al Hakam spores after exposure to PES-Solid (a solid source of peracetic acid), including PES-Solid formulations with bacteriostatic surfactants. METHODS AND RESULTS: Spores (≥ 7 logs) were dried on seven different test materials and treated with three different PES-Solid formulations (or preneutralized controls) at room temperature for 15 min. There was either no spore survival or less than 1 log (<10 spores) of spore survival in 56 of 63 test combinations (strain, formulation and substrate). Less than 2.7 logs (<180 spores) survived in the remaining seven test combinations. The highest spore survival rates were seen on water-dispersible chemical agent resistant coating (CARC-W) and Naval ship topcoat (NTC). Electron microscopy and Coulter analysis showed that all spore structures were intact after spore inactivation with PES-Solid. CONCLUSIONS: Three PES-Solid formulations inactivated Bacillus spores that were dried on seven different materials. SIGNIFICANCE AND IMPACT OF THE STUDY: A test method was developed to show that PES-Solid formulations effectively inactivate Bacillus spores on different materials.


Assuntos
Bacillus anthracis/efeitos dos fármacos , Bacillus thuringiensis/efeitos dos fármacos , Descontaminação/métodos , Desinfetantes/farmacologia , Ácido Peracético/farmacologia , Bacillus anthracis/ultraestrutura , Bacillus thuringiensis/ultraestrutura , Desinfetantes/química , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/ultraestrutura
8.
J Appl Microbiol ; 113(5): 1037-51, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22897143

RESUMO

AIMS: To develop test methods and evaluate the survival of Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores after exposure to hot, humid air. METHODS AND RESULTS: Spores (>7 logs) of both strains were dried on six different test materials. Response surface methodology was employed to identify the limits of spore survival at optimal test combinations of temperature (60, 68, 77°C), relative humidity (60, 75, 90%) and time (1, 4, 7 days). No spores survived the harshest test run (77°C, 90% r.h., 7 days), while > 6·5 logs of spores survived the mildest test run (60°C, 60% r.h., 1 day). Spores of both strains inoculated on nylon webbing and polypropylene had greater survival rates at 68°C, 75% r.h., 4 days than spores on other materials. Electron microscopy showed no obvious physical damage to spores using hot, humid air, which contrasted with pH-adjusted bleach decontamination. CONCLUSIONS: Test methods were developed to show that hot, humid air effectively inactivates B. anthracis ∆Sterne and B. thuringiensis Al Hakam spores with similar kinetics. SIGNIFICANCE AND IMPACT OF THE STUDY: Hot, humid air is a potential alternative to conventional chemical decontamination.


Assuntos
Bacillus anthracis/isolamento & purificação , Bacillus thuringiensis/isolamento & purificação , Descontaminação/métodos , Temperatura Alta , Umidade , Ar , Microscopia Eletrônica de Transmissão , Esporos Bacterianos/isolamento & purificação , Esporos Bacterianos/ultraestrutura , Estatística como Assunto
9.
J Thromb Haemost ; 9(2): 282-92, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21091865

RESUMO

BACKGROUND: Bleeding after cardiopulmonary bypass (CPB) is a major cause of morbidity and mortality and consumes large amounts of blood. Identifying patients at increased risk of bleeding secondary to hemostatic impairment may improve clinical outcomes by allowing early intervention. METHODS: This present study recruited 77 patients undergoing CPB and measured coagulation screens, coagulation factors, TEG(®), Rotem(®) and thrombin generation (TG) before surgery and 30 min after heparin reversal. The tests were analyzed to investigate whether they identified patients at increased risk of excess bleeding (defined as > 1000 mL) in the first 24 h postoperatively. RESULTS: Patients who bled > 1000 mL had a lower: platelet count (P < 0.02), factors (F)IX, X and XI (P < 0.005), endogenous thrombin potential (ETP) and an initial rate of TG (P < 0.02) and higher activated partial thromboplastin time (aPTT) (P < 0.001) than patients who bled < 1000 mL. Receiver operating characteristic (ROC) analysis was significant for post-operative TG and aPTT (P < 0.001). Furthermore, reduced pre-operative TG was associated with increased postoperative bleeding (P < 0.02). Pre- and postoperative TG were correlated (ρ = 0.7, P < 0.001). TEG(®), Rotem(®) and prothrombin time (PT) at either time point were not associated with increased bleeding. CONCLUSION: These data suggest that pre-operative defects in the propagation phase of hemostasis are exacerbated during CPB, contributing to bleeding post-CPB. TG taken both pre- and postoperatively could potentially be used to identify patients at an increased risk of bleeding post-CPB.


Assuntos
Ponte de Artéria Coronária , Hemorragia Pós-Operatória , Trombina/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Calibragem , Hemostasia , Humanos , Pessoa de Meia-Idade , Curva ROC
10.
J Appl Microbiol ; 105(5): 1604-13, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19146496

RESUMO

AIMS: To compare physical properties of spores that were produced in broth sporulation media at greater than 10(8) spores ml(-1). METHODS AND RESULTS: Bacillus atrophaeus reproducibly sporulated in nutrient broth (NB) and sporulation salts. Microscopy measurements showed that the spores were 0.68 +/- 0.11 microm wide and 1.21 +/- 0.18 microm long. Coulter Multisizer (CM3) measurements revealed the spore volumes and volume-equivalent spherical diameters, which were 0.48 +/- 0.38 microm(3) and 0.97 +/- 0.07 microm, respectively. Bacillus cereus reproducibly sporulated in NB, sporulation salts, 200 mmol l(-1) glutamate and antifoam. Spores were 0.95 +/- 0.11 microm wide and 1.31 +/- 0.17 microm long. Spore volumes were 0.78 +/- 0.61 microm(3) and volume-equivalent spherical diameters were 1.14 +/- 0.11 microm. Bacillus atrophaeus spores were hydrophilic and B. cereus spores were hydrophobic. However, spore hydrophobicity was significantly altered after treatment with pH-adjusted bleach. CONCLUSIONS: The utility of a CM3 for both quantifying Bacillus spores and measuring spore sizes was demonstrated, although the volume between spore exosporium and spore coat was not measured. This study showed fundamental differences between spores from a Bacillus subtilis- and B. cereus-group species. SIGNIFICANCE AND IMPACT OF THE STUDY: This is useful for developing standard methods for broth spore production and physical characterization of both living and decontaminated spores.


Assuntos
Bacillus/fisiologia , Meios de Cultura/química , Bacillus/ultraestrutura , Ácido Glutâmico , Microscopia Eletrônica , Sais , Esporos Bacterianos/fisiologia , Esporos Bacterianos/ultraestrutura
11.
J Bacteriol ; 187(24): 8278-90, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16321932

RESUMO

Bacillus spores are protected by a structurally and biochemically complex protein shell composed of over 50 polypeptide species, called the coat. Coat assembly in Bacillus subtilis serves as a relatively tractable model for the study of the formation of more complex macromolecular structures and organelles. It is also a critical model for the discovery of strategies to decontaminate B. anthracis spores. In B. subtilis, a subset of coat proteins is known to have important roles in assembly. Here we show that the recently identified B. subtilis coat protein CotO (YjbX) has an especially important morphogenetic role. We used electron and atomic force microscopy to show that CotO controls assembly of the coat layers and coat surface topography as well as biochemical and cell-biological analyses to identify coat proteins whose assembly is CotO dependent. cotO spores are defective in germination and partially sensitive to lysozyme. As a whole, these phenotypes resemble those resulting from a mutation in the coat protein gene cotH. Nonetheless, the roles of CotH and CotO and the proteins whose assembly they direct are not identical. Based on fluorescence and electron microscopy, we suggest that CotO resides in the outer coat (although not on the coat surface). We propose that CotO and CotH participate in a late phase of coat assembly. We further speculate that an important role of these proteins is ensuring that polymerization of the outer coat layers occurs in such a manner that contiguous shells, and not unproductive aggregates, are formed.


Assuntos
Bacillus subtilis/fisiologia , Proteínas de Bactérias/fisiologia , Esporos Bacterianos/ultraestrutura , Proteínas de Bactérias/análise , Proteínas de Bactérias/genética , Deleção de Genes , Proteínas de Fluorescência Verde/análise , Substâncias Macromoleculares/metabolismo , Microscopia de Força Atômica , Microscopia Eletrônica , Microscopia de Fluorescência , Modelos Biológicos , Morfogênese , Mutagênese Insercional , Esporos Bacterianos/química
12.
Ann Biomed Eng ; 32(2): 257-63, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15008373

RESUMO

Calculation of residual stress in arteries, using the analytical approach has been quite valuable in our understanding of its critical role in vascular mechanics. Stresses are calculated at the central section of an infinitely long tube by imposing a constant axial stretch while deforming the artery from the stress-free state to its unloaded state. However, segments used to perform opening-angle measurements have finite lengths. Further, the stress-free artery configuration is assumed to be circular. Experiments show that they are slightly noncircular. The numerical approach to residual stress calculation can allow us to study both these issues. Using 3D cylindrical geometries and an isotropic material model, we investigated how segment length can affect residual stress calculations and identified the appropriate segment length for experiments. Further, we recorded and used the true noncircular stress-free state of an artery segment, computed the residual stress distribution, and compared it to that from a similar, but circular segment. Our findings suggest that segment length must be ten times the wall thickness for it to be "long" enough. We also found that the circularity assumption may be a reasonable approximation for typical arteries.


Assuntos
Artéria Femoral/fisiologia , Modelos Cardiovasculares , Animais , Simulação por Computador , Elasticidade , Artéria Femoral/anatomia & histologia , Análise de Elementos Finitos , Técnicas In Vitro , Estresse Mecânico , Suínos
13.
Med Eng Phys ; 25(4): 289-98, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12649013

RESUMO

Atherosclerosis is a diffuse arterial disease developing over many years and resulting in a complicated three-dimensional arterial morphology. The arterial wall material properties have been demonstrated to show regional alterations with atheroma development and growth. We present a mechanical analysis of diseased arterial segments reconstructed from intravascular ultrasound images in order to quantitatively identify regional alterations in the elastic constants with atherosclerotic lesions. We employ a finite element and a displacement sensitivity analysis to divide the arterial segment into regions with different material properties and use an optimization algorithm to identify the elastic constants in these regions. The results with regional variations identified with this method correlated qualitatively with the extent and location of atherosclerotic lesions identified by visual inspection of the affected arteries. The optimized elastic modulus in regions affected by early atherosclerotic lesions ranged from 90.9 to 93.0 kPa where as the corresponding magnitudes in normal arterial segments ranged from 97.9 to 101.0 kPa. This method can be potentially employed to identify the extent and location of atherosclerotic lesions in a systematic analysis and may potentially be used for the early detection of lesion growth.


Assuntos
Arteriosclerose/diagnóstico por imagem , Arteriosclerose/fisiopatologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Modelos Cardiovasculares , Animais , Simulação por Computador , Elasticidade , Estudos de Viabilidade , Estresse Mecânico , Suínos , Ultrassonografia de Intervenção/métodos
14.
Echocardiography ; 18(7): 553-7, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11737963

RESUMO

UNLABELLED: Human studies have suggested that Doppler transesophageal echocardiography (TEE) can determine normal physiologic coronary blood flow (CBF) and alterations in CBF due to proximal flow-limiting stenoses. However, assessment of CBF by Doppler TEE has not been validated. To determine if true estimation of CBF could be obtained with Doppler TEE, seven mongrel dogs (weight range 28 kg-36 kg) were evaluated. Simultaneous CBF determinations by Doppler TEE and epicardial electromagnetic flow (EMF) and/or epicardial Doppler flow (EDF) probes were compared. Measurements were obtained at baseline and following varying degrees of proximal coronary occlusion, which produced reactive hyperemia. RESULTS: Consistent Doppler flow waveforms were obtainable by Doppler TEE in 34 different measurements during perturbations: Mean for TEE Flow (ml/min) = 85, EMF or EDF Flow (ml/min) = 53; Standard Deviation for TEE Flow (ml/min) = 45, EMF or EDF Flow (ml/min) = 38; Minimum for TEE Flow (ml/min) = 42, EMF or EDF Flow (ml/min) = 11; and Maximum for TEE Flow (ml/min) = 174, EMF or EDF Flow (ml/min) = 130. TEE Flow (ml/min) = 1.1 EMF/EDF flow + 26.3. There was a general trend towards overestimation of CBF by Doppler TEE. This study demonstrates that Doppler TEE is a promising method for obtaining measurements of CBF over the physiologic range.


Assuntos
Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Ecocardiografia Transesofagiana/métodos , Animais , Velocidade do Fluxo Sanguíneo , Intervalos de Confiança , Cães , Modelos Lineares , Modelos Animais , Probabilidade , Valores de Referência , Sensibilidade e Especificidade , Ultrassonografia Doppler/métodos
15.
J Pharm Sci ; 90(12): 1917-26, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11745750

RESUMO

Targeted echogenic liposome dispersions for ultrasonic enhancement of vasoactive and pathological components of endothelium and atherosclerosis have recently been developed. The component lipids required for acoustic and targeting properties include phosphatidylcholine, phosphatidylethanolamine phosphatidylglycerol (PG), and cholesterol (CH), initially in a 60:8:2:30 mol % ratio. Component lipids, lyophilization, sugars, and freezing conditions were varied to optimize acoustic ultrasound reflectivity and acoustic stability. Echogenic liposome dispersions were made by using the dehydration-rehydration process. The lipid concentrations were varied (CH in the range 1 to 40 mol % and PG from 1 to 16 mol %). Variations in type and concentration of sugars were examined. The effect of freezing conditions and re-lyophilization was examined. Ultrasound reflectivity was assessed by using a 20-MHz intravascular ultrasound catheter and computer-assisted videodensitometry. Ultrasound reflectivity was optimized at a CH concentration of 10 mol %; PG concentration variation had essentially no effect on initial values of echogenicity. Optimal acoustic stability was observed with concentrations of 10-15 mol % CH and with a PG concentration greater than 4 mol %. Preparations made with 0.2 M mannitol were more ultrasound reflective than those made with lactose, trehalose, and sucrose. Re-lyophilization and freezing temperatures below -20 degrees C increased ultrasound reflectivity. We optimized the ultrasound properties of echogenic liposomal dispersions, the conditions of which provide some insight into the underlying lipid structures responsible. The preparations developed are now more stable and acoustically reflective than our previous preparations. This advances the development of echogenic lipid dispersions as targeted ultrasound contrast agents for use in general ultrasound as well as cardiovascular imaging.


Assuntos
Meios de Contraste/química , Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Ultrassom , Carboidratos/química , Colesterol/química , Liofilização , Fosfatidilgliceróis/química , Gravação de Videoteipe
16.
Acta Crystallogr D Biol Crystallogr ; 57(Pt 12): 1908-11, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11717514

RESUMO

A complex between interleukin-10 and the extracellular domain of its high-affinity receptor (sIL-10R1) has been crystallized from polyethylene glycol solutions. Crystals suitable for diffraction analysis required the modification of the NXS/T glycosylation sites on sIL-10R1 by site-directed mutagenesis and inclusion of the detergent cyclohexyl-methyl-beta-D-maltopyranoside in the crystallization experiments. The crystals belong to space group P3(2)12 or its enantimorph P3(1)12, with unit-cell parameters a = b = 46.23, c = 307.78 A, alpha = beta = 90, gamma = 120 degrees, and diffract X-rays to approximately 2.9 A. The IL-10 dimer is positioned on a crystallographic twofold, resulting in one IL-10 chain and one sIL-10R1 chain in the asymmetric unit, which corresponds to a solvent content of approximately 44%.


Assuntos
Interleucina-10/química , Receptores de Interleucina/química , Animais , Clonagem Molecular , Cristalização , Cristalografia por Raios X , Drosophila/química , Conformação Proteica , Receptores de Interleucina-10 , Solubilidade
17.
Nucl Med Biol ; 28(8): 959-73, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11711316

RESUMO

1-Methylpiperidin-4-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IPIP, Fig. 1) was investigated as a potential radioiodinated molecular probe targeted to the muscarinic receptor complex. The IPIP stereoisomers were synthesized via a chiral intermediate in >95% enantiomeric excess. The R-isomers demonstrated a M(1) to M(2) subtype selectivity of approximately 3 to 1 and the S-isomers demonstrated non-subtype selective binding in vitro. IPIP was radiolabeled with iodide-125 with an average radiochemical yield of 74.4% (+/-14.8, n = 5), specific activities >800 mCi/micromol, and radiochemical purities >97%. In vivo the Z-isomers demonstrated high uniform cerebral uptake suggesting non-subtype selective binding. In contrast, E-R-IPIP, after allowing a low uptake in M(2) rich areas to clear, demonstrated a retention of activity in M(1) and M(4) rich cerebral regions. In addition, the cerebral uptake of E-R-IPIP and Z-S-IPIP were inhibited by 70-90% via pretreatment with R-QNB, an established muscarinic antagonist. An ex vivo metabolism study demonstrated Z-S-IPIP was stable at the receptor site with an absence of radiolabeled metabolites.


Assuntos
Sondas Moleculares/síntese química , Fenilacetatos/síntese química , Piperidinas/síntese química , Receptores Muscarínicos/metabolismo , Animais , Feminino , Sondas Moleculares/química , Sondas Moleculares/farmacocinética , Fenilacetatos/química , Fenilacetatos/farmacocinética , Piperidinas/química , Piperidinas/farmacocinética , Quinuclidinil Benzilato/análogos & derivados , Ratos , Estereoisomerismo , Relação Estrutura-Atividade , Distribuição Tecidual
18.
Med Eng Phys ; 23(8): 583-95, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11719081

RESUMO

Previous studies have indicated a correlation between local variation in wall shear stress in arterial blood flow and atheroma development. The purpose of this study was to analyze the hemodynamics in vascular segments from morphologically realistic three-dimensional (3D) reconstruction, and to compare the computed wall shear stress in a compliant vascular segment model and the corresponding rigid walled model. Cross-sectional images of the segments of femoral and carotid arteries in five Yucatan miniswine were obtained using intravascular ultrasound (IVUS) imaging and the segment geometry was reconstructed at different times in the cardiac cycle. The actual measured wall motion from the reconstruction was employed to specify the moving boundaries for simulation of physiological distensibility. Velocity profiles and wall shear stress were computed using unsteady computational fluid dynamics analysis. The computed results revealed that the maximum wall shear stress in the compliant model was approximately 4-17 percent less than that in the rigid model if the wall motion is larger than 10 percent. Our analysis demonstrates that inaccuracies due to inflow velocity profile can be minimized by the extension of the model upstream. The phase angle between the diameter change and wall shear is affected by the local changes in geometry of the arteries. These simulations can be potentially used to analyze the effect of regional wall motion changes in the presence of atherosclerotic lesions on the local fluid dynamics and to correlate the same with subsequent growth of the lesions.


Assuntos
Artérias/diagnóstico por imagem , Artérias/patologia , Fluxo Pulsátil , Ultrassom , Animais , Artérias Carótidas/diagnóstico por imagem , Cateterismo , Simulação por Computador , Elasticidade , Eletrocardiografia , Artéria Femoral/diagnóstico por imagem , Hemodinâmica , Modelos Estatísticos , Estresse Mecânico , Porco Miniatura , Fatores de Tempo , Ultrassonografia
19.
Cardiovasc Pathol ; 10(4): 179-88, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11600335

RESUMO

BACKGROUND: Bioprosthetic heart valve use is limited by progressive degeneration. Early degenerative changes are often occult, making assessment of tissue integrity difficult. Ultrasound tissue characterization may detect alterations in tissue structure and allow early detection of leaflet degeneration. METHODS: Using a modified echocardiographic unit (Acuson), radiofrequency (RF) integrated backscatter amplitude (IBA) (integral/RF/dt) was measured in 38 leaflets from nine explanted and six control porcine valves. Regions of interest in each leaflet were studied using four ultrasound frequencies. Radiographic gray scale mean and leaflet thickness were measured at each region of interest. Percent collagen and mineral were calculated for each region of interest using color-image processing of histologic sections and compared to IBA. RESULTS: IBA values for control vs. explanted leaflets were (mean value+/-standard deviation): 8.2+/-4.69 dB vs. -4.7+/-4.64 dB at 7.0 MHz; -5.8+/-4.34 dB vs. -3.1+/-5.34 dB at 5.0 MHz; -3.8+/-3.38 dB vs. -2.1+/-3.18 dB at 3.5 MHz; and -9.0+/-4.58 dB vs. -7.1+/-4.25 dB at 2.5 MHz. Collagen content was 27.7+/-8.50% vs. 33.2+/-10.90%, mineral content was 0.1+/-0.10% vs. 2.1+/-4.30%, and radiographic gray scale mean was 150.6+/-1.96 vs. 145.3+/-5.14 for control vs. explanted leaflets, respectively. For control and explanted leaflets IBA, collagen content, mineral content, and radiographic gray scale mean were different (control vs. explanted P<0.05). Leaflet thickness was also noted to be different between the two groups. IBA was different among explanted leaflets with low, medium, and high mineral content. CONCLUSION: IBA was found to be a useful technique to differentiate normal from explanted porcine prosthetic valves in vitro. This method may be useful in the serial assessment of bioprosthetic leaflet degenerative properties in vivo.


Assuntos
Bioprótese , Ecocardiografia/métodos , Próteses Valvulares Cardíacas , Adulto , Idoso , Animais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Calcinose , Cálcio/análise , Colágeno/análise , Ecocardiografia/instrumentação , Feminino , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Processamento de Imagem Assistida por Computador , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Valva Mitral/cirurgia , Ondas de Rádio , Suínos , Fatores de Tempo , Ultrassonografia
20.
J Am Soc Echocardiogr ; 14(10): 994-1000, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11593204

RESUMO

The objective of this study was to validate a real-time 3-dimensional echocardiography (3DE) technique for the determination of left ventricular (LV) volume and ejection fraction (EF). In 10 mongrel dogs, an electromagnetic flow (EMF) probe was placed on the aorta, and the thorax was closed. Transthoracic imaging was performed during multiple hemodynamic conditions (n = 58) with simultaneous measurement of stroke volume (SV) with the use of EMF. From the volumetric data set, LV volumes were manually traced off-line by 2 independent observers with an apical rotation method (6 planes) and a conventional method (biplane) in a subset of conditions. This tracing technique was also evaluated in 18 human subjects in whom the calculated EF values were compared with values derived by multigated radionuclide angiography (MUGA). Excellent correlation and close limits of agreement were noted between SV measured by 3DE and EMF (r = 0.93) in dogs. In comparison with EMF-derived SV, 3DE provided better correlation than the biplane method (r = 0.93 versus r = 0.61). Interobserver and intraobserver variabilities were comparable (r = 0.94 and r = 0.94, respectively). In a comparison of MUGA-derived EF values and those obtained by 3DE in human subjects, 3DE provided better correlation than the biplane method (r = 0.94 versus r = 0.85). Real-time 3DE accurately measures left ventricular volumes transthoracically over a wide range of hemodynamic conditions in dogs and accurately determines EF in humans.


Assuntos
Ecocardiografia Tridimensional/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Cães , Estudos de Viabilidade , Imagem do Acúmulo Cardíaco de Comporta , Hemodinâmica , Humanos , Modelos Lineares , Volume Sistólico , Fatores de Tempo , Função Ventricular Esquerda
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