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1.
Vet Ophthalmol ; 27(2): 114-126, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37199512

RESUMEN

OBJECTIVE: Assess the utility of a Sub-Tenon's anesthesia (STA) protocol to provide suitable operating conditions for canine cataract surgery and compare it to an alternative low-dose neuromuscular blockade (LD-NMB) protocol used for canine cataract surgery. PROCEDURES: Clinical study of dog eyes undergoing cataract surgery with either an STA or LD-NMB protocol. While intraoperative vitreal expansion scores and intraoperative complications were collected prospectively, globe position, intraocular pressure, return of vision, and postoperative complications were collected retrospectively. Statistical testing was used to compare results between the STA and the LD-NMB groups for the data available. RESULTS: A total of 224 eyes from 126 dogs were assessed, with 133/224 (59.4%) eyes from 99/126 (78.6%) dogs receiving STA and 91/124 (40.6%) eyes from 72/126 (57.1%) dogs receiving LD-NMB. Forty-five of these dogs (45/126; 37.7%) received STA for one eye and LD-NMB for the other eye. There was no significant change in intraocular pressure measurements following STA administration. This was not measured for the LD-NMB group. The globe achieved a central position in 110/133 (82.7%) of eyes that received STA. This was not measured for the LD-NMB group. Intraoperative vitreal expansion scores were slightly higher in STA-treated eyes compared to LD-NMB-treated eyes. The intraoperative complication rate for STA-treated eyes was higher (73/133; 54.8%) compared to NMB-treated eyes (12/91; 13.2%). The most common intraoperative complication for STA was chemosis (64/133; 48.1%), the risk of which increased with an increase in the volume of local anesthetic injected. The post-operative complication rate was higher in STA-treated eyes (28/133; 21.1%) compared to NMB-treated eyes (16/91; 17.6%). Post-operative corneal ulceration was the most common postoperative complication in STA-treated eyes (6/133; 4.5%). CONCLUSION: The STA protocol described resulted in suitable operating conditions, but more intraoperative and postoperative complications compared to the LD-NMB protocol. Despite these complications, the STA protocol did not cause a significant deleterious impact on post-operative outcomes as defined in the present study.


Asunto(s)
Catarata , Enfermedades de los Perros , Bloqueo Neuromuscular , Facoemulsificación , Perros , Animales , Bloqueo Neuromuscular/veterinaria , Estudios Retrospectivos , Facoemulsificación/veterinaria , Anestésicos Locales , Anestesia Local/veterinaria , Complicaciones Posoperatorias/veterinaria , Catarata/veterinaria , Complicaciones Intraoperatorias/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/cirugía
2.
Vet Ophthalmol ; 22(4): 485-492, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30365226

RESUMEN

OBJECTIVE: To analyze a study population of dogs with primary corneal endothelial degeneration (PCED) for information on the patterns of disease and to report the efficacy of superficial keratectomy (SK) for resolution of non-healing corneal ulcers associated with PCED. ANIMALS STUDIED: Primary corneal endothelial degeneration was diagnosed in 238 dogs between 1998 and 2017. Corneal ulceration associated with PCED was present in 89 dogs (109 eyes), of which 47 eyes were treated with SK. PROCEDURES: A retrospective assessment of medical records was performed to determine the signalment patterns of PCED, and the success rate of the SK procedure for resolving PCED-associated corneal ulceration. Descriptive statistics were reported on the signalment of PCED cases, with odd ratios and confidence intervals calculated to detect breed predispositions. RESULTS: Primary corneal endothelial degeneration was diagnosed in 238 dogs, 40.8% were female and 59.2% were male, with a mean age at diagnosis of 11.4 years. Dachshunds, Dalmatians, English Springer Spaniels, Welsh Springer Spaniels, Chihuahuas, Cocker Spaniels, and Golden Retrievers were significantly over-represented. All PCED-affected Dalmatians developed associated corneal ulceration. Follow-up information was available for 41/47 eyes treated with SK. At the first reassessment, 87.8% were healed which increased to 97.6% with subsequent monitoring. Four eyes (9.8%) had late corneal ulcer occurrence following SK, at a median time following SK of 182 weeks post-surgery. CONCLUSIONS: Superficial keratectomy was an effective option for resolving painful non-healing corneal ulcers associated with PCED. Dalmatians may be at increased risk of developing PCED-associated corneal ulceration.


Asunto(s)
Enfermedades de la Córnea/veterinaria , Úlcera de la Córnea/veterinaria , Enfermedades de los Perros/cirugía , Queratectomía/veterinaria , Animales , Enfermedades de la Córnea/complicaciones , Enfermedades de la Córnea/cirugía , Úlcera de la Córnea/etiología , Úlcera de la Córnea/cirugía , Perros , Femenino , Masculino , Estudios Retrospectivos
3.
Vet Ophthalmol ; 21(6): 601-611, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29411508

RESUMEN

OBJECTIVE: To test a sub-Tenon's anesthesia technique in dogs as an alternative to systemic neuromuscular blockade to aid in canine cataract surgery under general anesthesia. PROCEDURES: A prospective controlled clinical study was performed involving 12 dogs undergoing bilateral cataract surgery under general anesthesia. One eye was randomly assigned to have phacoemulsification and prosthetic lens implantation performed with sub-Tenon's anesthesia (STA), and the control eye had surgery performed with systemic neuromuscular blockade (NMB). Intraocular pressure (IOP) was measured immediately before and after STA administration. Globe position, globe rotation, pupillary dilation, and vitreal expansion were assessed for both STA and NMB eyes during surgery. RESULTS: Sub-Tenon's anesthesia produced a globe position suitable for cataract surgery with the degree of vitreal expansion not significantly different to control NMB eyes. STA produced greater anterior globe displacement than NMB in all cases. STA had no significant effect on IOP. CONCLUSION: Sub-Tenon's anesthesia was an effective alternative to systemic neuromuscular blockade for canine cataract surgery and may be beneficial for surgical exposure in deep orbited breeds.


Asunto(s)
Anestesia de Conducción/veterinaria , Catarata/veterinaria , Enfermedades de los Perros/cirugía , Implantación de Lentes Intraoculares/veterinaria , Facoemulsificación/veterinaria , Cápsula de Tenon , Anestesia de Conducción/métodos , Animales , Bupivacaína/administración & dosificación , Perros , Femenino , Presión Intraocular/efectos de los fármacos , Masculino , Bloqueo Neuromuscular/veterinaria , Nervio Oculomotor/efectos de los fármacos , Distribución Aleatoria , Cápsula de Tenon/efectos de los fármacos
4.
Osteoarthritis Cartilage ; 21(1): 226-36, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23069853

RESUMEN

OBJECTIVE(S): Meniscectomy (MX) of sheep induces a well-established animal model of human osteoarthritis (OA). This study compared the clinical (lameness) and pathological outcomes of unilateral, complete medial MX vs two less traumatic and more easily performed meniscal destabilisation procedures. METHODS: Four-year old wethers (n = 6/group) underwent sham operation, cranial pole release (CPR), mid-body transection (MBT) or total MX of the medial meniscus. Joints were assessed for gross pathology (cartilage erosion and osteophytes), histomorphometry, two histopathology scoring methods (modified Mankin-type and Pritzker score), and immunohistology for ADAMTS- and MMP-cleaved neoepitopes, at 12 weeks post-op. Ground reaction forces (GRFs) were determined by force plate in a subset (n = 4/group) at baseline, 2.5, 8, and 12 weeks post-op. RESULTS: Gross pathology scores of operated groups differed significantly from sham animals (P < 0.05) but not from each other, though qualitative differences were noted: CPR sheep developed more cranial and focal lesions, while MBT and MX joints showed more widespread lesions and osteophyte formation. Similarly, histopathology scores were significantly elevated vs sham but did not differ between operated groups at P < 0.05, except for a trend for lower tibial cartilage histopathology in MBT consistent with the immunohistologic pattern of reduced aggrecanase-cleavage neoepitope in that model. CPR sheep developed less femoral subchondral sclerosis, suggesting some residual biomechanical effect from the destabilised but intact meniscus. Few significant differences were noted between operated groups in force plate analyses, though gait abnormalities appeared to be least in CPR sheep, and most persistent (>12 weeks) in MBT animals. CONCLUSION: The well-validated ovine MX model and the simpler meniscal destabilisation procedures resulted in broadly similar joint pathology and lameness. Meniscal CPR or MBT, as easier and more clinically relevant procedures, may represent preferred models for the induction of OA and evaluation of potential disease-modifying therapies.


Asunto(s)
Cartílago Articular/patología , Marcha/fisiología , Meniscos Tibiales/patología , Osteoartritis de la Rodilla/patología , Animales , Artritis Experimental , Endopeptidasas/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Meniscos Tibiales/cirugía , Osteofito/patología , Ovinos
5.
Osteoarthritis Cartilage ; 19(7): 874-85, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21619935

RESUMEN

OBJECTIVES: To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation. METHODS: SOST and other Wnt-ß-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA and protein expression by ovine chondrocytes in response to interleukin-1α (IL-1α) or tumour necrosis factor-α (TNFα) was examined in explant cultures. The effect of 25 or 250 ng/ml recombinant SOST alone or in combination with IL-1α, on ovine articular cartilage explant aggrecan degradation, and chondrocyte gene expression of Wnt-ß-catenin pathway proteins, metalloproteinases and their inhibitors, and cartilage matrix proteins was quantified. RESULTS: Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and mRNA levels were upregulated in vitro by IL-1α but not TNFα. Chondrocyte SOST staining was significantly increased only in the focal area of cartilage damage in surgically-induced OA in sheep and mice, as well as end-stage human OA. In contrast, osteocyte SOST was focally decreased in the subchondral bone in sheep OA in association with bone sclerosis. SOST was biologically active in chondrocytes, inhibiting Wnt-ß-catenin signalling and catabolic metalloproteinase [matrix metalloproteinases (MMP) and distintegrin and metalloproteinase with thrombospndin repeats (ADAMTS)] expression, but also decreasing mRNA levels of aggrecan, collagen II and tissue inhibitors of metalloproteinaes (TIMPs). Despite this mixed effect, SOST dose-dependently inhibited IL-1α-stimulated cartilage aggrecanolysis in vitro. CONCLUSIONS: These results implicate SOST in regulating the OA disease processes, but suggest opposing effects by promoting disease-associated subchondral bone sclerosis while inhibiting degradation of cartilage.


Asunto(s)
Proteínas Morfogenéticas Óseas/metabolismo , Cartílago Articular/metabolismo , Condrocitos/metabolismo , Osteoartritis de la Rodilla/metabolismo , Animales , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Condrocitos/efectos de los fármacos , Humanos , Interleucina-1alfa/farmacología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Osteoartritis de la Rodilla/patología , ARN Mensajero/metabolismo , Ovinos , Factor de Necrosis Tumoral alfa/farmacología
6.
Osteoarthritis Cartilage ; 18 Suppl 3: S80-92, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20864026

RESUMEN

OBJECTIVE: Sheep and goats are commonly used large animal species for studying pathogenesis and treatment of osteoarthritis (OA). This review focuses on the macroscopic and microscopic criteria for assessing OA in sheep and goats and recommends particular assessment criteria to assist standardization in the conduct and reporting of preclinical trials of OA. METHODS: A review was conducted of all published OA studies using sheep and goats and the most common macroscopic, microscopic, or ultrastructural scoring systems were summarised. General recommendations regarding methods of OA assessment in the sheep and goat have been made and a preliminary study of their reliability and utility was undertaken. RESULTS: The modified Mankin scoring system is recommended for semiquantitative histological assessment of OA due to its already widespread adoption, ease of use, similarity to scoring systems used for OA in humans, and its achievable inter-rater reliability. Specific recommendations are also provided for histological scoring of synovitis and scoring of macroscopic lesions of OA. CONCLUSIONS: The proposed system for assessment of sheep and goat articular tissues appears to provide a useful versatile method to quantify OA change. It is hoped that by adopting more standardised quantitative outcome measures, better comparison between different studies and arthritis models will be possible. The suggested scoring systems can be modified in the future as our knowledge of disease pathophysiology advances.


Asunto(s)
Artritis Experimental/patología , Osteoartritis/patología , Animales , Cartílago Articular/patología , Modelos Animales de Enfermedad , Cabras , Articulaciones/patología , Índice de Severidad de la Enfermedad , Ovinos , Membrana Sinovial/patología
7.
Rheumatology (Oxford) ; 47(8): 1172-8, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18565987

RESUMEN

OBJECTIVE: IA therapy with hyaluronan (HA) is reported to provide symptomatic relief and disease modification in OA. This study assessed the pathological changes in the synovium of an ovine model of OA and evaluated the effects of two HA preparations on this pathology. METHODS: Eighteen sheep had bilateral lateral meniscectomy to induce OA. Four months post-surgery animals received IA saline or HA (Hyalgan) weekly for 5 weeks or three injections of an amide derivative of HA (HYADD 4-G) every 2 weeks (n = 6 per group). Six months after meniscectomy, sheep were killed, knee joint synovium processed, scored for pathological change and compared with synovium from non-operated animals. Sections of synovium from normal and treated joints were also immunostained for TNF-alpha, HSP-47, TGF-beta, CD44, connective tissue growth factor (CTGF) or iNOS. HA synthesis by synovial fibroblasts isolated from each OA joint was quantified. RESULTS: Aggregate scores of pathological change were higher in OA joint synovia compared with controls, with individual measures of subintimal fibrosis and vascularity predominantly affected. Depth of intimal fibrosis was also significantly higher in meniscectomized joints. IA treatment with Hyalgan decreased aggregate score, vascularity and depth of fibrosis. HYADD 4-G treatment decreased vascularity, intimal hyperplasia and increased high-molecular weight HA synthesis by synovial fibroblasts. CD44, CTGF or iNOS expression was increased in the synovial lining of OA joints compared with normal, but there was no significant modulation of this increase by either HA preparation. CONCLUSION: Increased fibrosis and vascularity are hallmarks of pathological change in synovium in this meniscectomy model of OA. Both the IA HA and an amide derivative of HA reduced aspects of this pathology thus providing a potential mechanism for improving joint mobility and function in OA.


Asunto(s)
Artritis Experimental/tratamiento farmacológico , Ácido Hialurónico/uso terapéutico , Osteoartritis/tratamiento farmacológico , Membrana Sinovial/patología , Animales , Artritis Experimental/etiología , Artritis Experimental/patología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Fibroblastos/metabolismo , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/biosíntesis , Inyecciones Intraarticulares , Meniscos Tibiales/cirugía , Osteoartritis/etiología , Osteoartritis/patología , Oveja Doméstica , Membrana Sinovial/metabolismo
8.
Clin Exp Rheumatol ; 26(4): 561-7, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18799085

RESUMEN

OBJECTIVES: Published scoring methods for quantifying synovitis focus on acute inflammatory parameters, and are unsuitable as outcome measures in experimental surgical models of osteoarthritis (OA). The aim of the present study was to define a modified histopathological scoring system for ovine synovium more suited to the chronic pathology induced by ovine meniscectomy, and to apply it to detect any therapeutic effects following intraarticular injection of hyaluronan (HA) (Hyalgan). METHODS: OA was induced in 12 sheep by bilateral lateral meniscectomy, before weekly intraarticular injections of HA or saline vehicle from 16-20 weeks post-operatively, prior to sacrifice at 26 weeks. Six matched sheep were used as controls. Synovial sections were qualitatively scored for hyperplasia, inflammatory infiltrate, fibrosis, and hypervascularity; cell number, depth of fibrosis, and vessel number were also quantified using a graticule. RESULTS: OA synovia had significantly elevated scores for inflammatory cell infiltration, subintimal fibrosis, vascularity, and aggregate score relative to controls. HA-treated sheep had significantly lower vascularity score (p=0.015), aggregate score (p=0.007), depth of fibrosis (p=0.003) and vessel number (p=0.048) compared to saline-injected sheep. CONCLUSION: This study confirms the presence of a chronic synovitis in this OA model, characterised by subintimal fibrosis and hypervascularity (but only modest infiltrate and minimal intimal hyperplasia), which is partially ameliorated by intraarticular hyaluronate therapy.


Asunto(s)
Ácido Hialurónico/administración & dosificación , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Membrana Sinovial/patología , Viscosuplementos/administración & dosificación , Animales , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Femenino , Fibrosis/tratamiento farmacológico , Hiperplasia/tratamiento farmacológico , Inyecciones Intraarticulares , Índice de Severidad de la Enfermedad , Oveja Doméstica , Membrana Sinovial/efectos de los fármacos
9.
Aust Vet J ; 85(6): 226-31, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17547635

RESUMEN

A 6-year-old desexed female German Shepherd dog was referred to the Murdoch University Veterinary Hospital for assessment and management of acute onset vomiting, diarrhoea, polydipsia and lethargy of 2 days duration. Surgical, microbiological and histological findings were consistent with necrotising cholecystitis secondary to gall bladder torsion, resulting in gall bladder rupture and secondary non-septic bile peritonitis. A chronic peritoneopleural perforation resulting from an abdominal cavity foreign body and congenital peritoneopericardial hernia were also present. The dog made a full recovery following cholecystectomy, foreign body removal, repair of the peritoneopleural perforation and peritoneopericardial herniorrhaphy. This is the first recorded case of gall bladder torsion in the dog.


Asunto(s)
Colecistitis/veterinaria , Enfermedades de los Perros/diagnóstico , Cuerpos Extraños/veterinaria , Enfermedades de la Vesícula Biliar/veterinaria , Peritonitis/veterinaria , Animales , Colecistectomía/métodos , Colecistectomía/veterinaria , Colecistitis/diagnóstico , Colecistitis/etiología , Colecistitis/cirugía , Enfermedades de los Perros/cirugía , Perros , Femenino , Cuerpos Extraños/complicaciones , Cuerpos Extraños/diagnóstico , Cuerpos Extraños/cirugía , Enfermedades de la Vesícula Biliar/complicaciones , Enfermedades de la Vesícula Biliar/diagnóstico , Enfermedades de la Vesícula Biliar/cirugía , Peritonitis/diagnóstico , Peritonitis/etiología , Peritonitis/cirugía , Rotura/veterinaria , Anomalía Torsional/complicaciones , Anomalía Torsional/diagnóstico , Anomalía Torsional/cirugía , Anomalía Torsional/veterinaria , Resultado del Tratamiento
10.
Aust Vet J ; 85(6): 212-6, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17547632

RESUMEN

Hip palpation has been used to provide semiquantitative information regarding passive joint laxity and susceptibility to hip dysplasia. The purpose of this study was to: (1) evaluate the intra- and inter-examiner repeatability of the hip reduction angle measured at 4 months of age by three examiners using manual goniometry and an electromagnetic tracking system; (2) compare the hip reduction angle measured with manual goniometry to the hip reduction angle measured with the electromagnetic tracking system; and (3) evaluate the hip reduction angle, distraction index and Ortolani manoeuvre at 4 months of age as predictors of the development of hip osteoarthritis at 12 months of age in 11 Labrador Retriever dogs. Intra- and inter-examiner repeatability was demonstrated for both the manual and electromagnetic goniometric measurement of the hip reduction angle (coefficient of variation < 4.3% and < 6.1%; and P = 0.163 and P = 0.836 respectively). The hip reduction angle measured by manual goniometry was moderately correlated to the hip reduction angle measured by the electromagnetic tracking system (r = 0.603, P < 0.0000). The hip reduction angle measured by manual and electromagnetic goniometry was a poor predictor of osteoarthritis at 12 months of age (r = 0.231, P < 0.062, and r = 0.321, P < 0.01). The distraction index was moderately correlated with the development of osteoarthritis by 12 months of age (r = 0.493, P < 0.0000). The Ortolani sign was sensitive (100%) but not specific (41%) for the development of osteoarthritis at 12 months of age. The hip reduction angle did not further quantify the Ortolani manoeuvre as a predictor of osteoarthritis in Labrador Retrievers.


Asunto(s)
Biometría/métodos , Enfermedades de los Perros/patología , Displasia Pélvica Canina/patología , Inestabilidad de la Articulación/veterinaria , Osteoartritis de la Cadera/veterinaria , Factores de Edad , Animales , Animales Recién Nacidos , Diagnóstico Diferencial , Enfermedades de los Perros/diagnóstico , Perros , Femenino , Displasia Pélvica Canina/complicaciones , Displasia Pélvica Canina/diagnóstico , Inestabilidad de la Articulación/complicaciones , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/patología , Masculino , Variaciones Dependientes del Observador , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/etiología , Palpación/veterinaria , Examen Físico/veterinaria , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad
11.
Radiat Res ; 93(1): 93-106, 1983 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-6681674

RESUMEN

We examined the dependence of heat killing and thermotolerance on the position and progression of Chinese hamster ovary (CHO) cells in the cell cycle. We measured cell cycle perturbations and survival of asynchronous and synchronized G1-, S-, and G2-phase cells resulting from continuous heating at 42.0 degrees C for up to 80 hr. Thermotolerance under these conditions was transient in nature, was dependent on the position of cells in the cell cycle, and occurred concurrently with a heat-induced delay of progression of G1- and G2-phase cells. When G1 cells were heated, survival decreased to 25% after 4 hr, at which time the thermotolerance was expressed. For G2 cells survival decreased initially at the same rate (T0 congruent to 3 hr) but thermotolerance was not expressed until approximately 12 hr, at which time the survival was 4%. The rate of decrease in survival was much more rapid for cells heated in mid-S phase (T0 congruent to 0.5 hr), and these cells did not express thermotolerance at a measurable level. Concurrent with the expression of thermotolerance, the progression of cells heated in G1 and G2 was delayed. Following the expression of tolerance, progression resumed at a rate approximately equal to the rate of decrease in survival of the G1 population. Cells heated in mid-S phase continued to progress through the cell cycle until they reached G2, where they were also delayed.


Asunto(s)
Ciclo Celular , Supervivencia Celular , Calor/uso terapéutico , Animales , Línea Celular , Cricetinae , Cricetulus , Femenino , Citometría de Flujo , Interfase , Neoplasias/terapia , Ovario , Factores de Tiempo
12.
Radiat Res ; 98(3): 491-505, 1984 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-6729049

RESUMEN

This report extends our investigations of the cell cycle dependence of the expression of thermotolerance to include tolerance expressed by Chinese hamster ovary (CHO) cells exposed to 45.0 degrees C hyperthermia. We examined the response of asynchronous cells following exposure at 45.0 degrees C. A maximum in thermotolerance under these conditions was reached approximately 12 hr after a 15-min exposure to 45.0 degrees C hyperthermia and progressively decreased thereafter. Cells were delayed in S and G2 phase for 24 hr, after which time cell growth resumed. We then characterized the response of CHO cell populations synchronized in G1 or early or late S phase. We observed that the expression of tolerance depended on the position of cells in the cell cycle and was modulated by changes in the sensitivity of cells as they progressed through the cell cycle subsequent to the tolerance induction dose. We measured the variation in the sensitivity of these cells to 45.0 degrees C hyperthermia throughout the cell cycle and found substantial changes as cells progressed through S phase. Cells in early S phase were the most sensitive to heat at this temperature, and as these cells progressed through S phase, they became progressively more resistant. In addition, G1 cells were delayed for approximately 15 to 18 hr by a 15-min, 45.0 degrees C heat pulse, whereas S-phase cells were delayed to a lesser extent. The data presented in this report suggest that the induction of thermotolerance is relatively non-cell-cycle specific, but the magnitude of expression of tolerance depends on the position of cells in the cell cycle at the time of the subsequent challenge heat dose.


Asunto(s)
Regulación de la Temperatura Corporal , Ciclo Celular , Temperatura , Animales , Células Cultivadas , Cricetinae , Cricetulus , Femenino , Citometría de Flujo , Interfase , Ovario/citología , Factores de Tiempo
13.
Radiat Res ; 104(3): 429-42, 1985 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-4080985

RESUMEN

We have extended our studies on the cell cycle dependence of thermotolerance to include HeLa cells heated at 45.0 degrees C to compare the results to Chinese hamster ovary (CHO) cells. We found that asynchronous HeLa cells were more resistant to heat than CHO cells but showed a similar development and decay of thermotolerance. Flow cytometry (FCM) was used to study redistributions in the cell cycle after an initial heat dose. Cells heated for 35 min at 45.0 degrees C were delayed in G1 by about 7 h compared to controls, with delays in late S and G2/M phase also. The heat sensitivity varied through the cell cycle; G1 cells were the most resistant to heat, while S-phase cells were uniformly sensitive throughout S phase, and G2 cells were resistant. Thermotolerance could be induced and expressed in early or late S-phase cells, but to a lesser extent than for G1 cells. The results were similar in many respects to CHO cells, but there were significant differences.


Asunto(s)
Aclimatación , Ciclo Celular , Células HeLa/fisiología , Calor , Citometría de Flujo , Humanos
14.
Surgery ; 114(2): 308-13, 1993 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8342134

RESUMEN

BACKGROUND: Our previous studies have implicated phospholipase A2-dependent platelet-activating factor (PAF) production in the genesis of polymorphonuclear neutrophil (PMN)-mediated tissue injury after gut ischemia-reperfusion. Further, these studies have suggested a discordance of PMN sequestration and tissue injury. CD11B-dependent PMN-endothelial cell adhesion has been purported to play a dominant role in PMN-mediated tissue injury. We therefore undertook this study with the hypothesis that PAF-induced PMN superoxide production requires CD11B-mediated PMN-endothelial cell adherence. METHODS: Human PMNs, isolated by Percoll gradient centrifugation, were exposed to PAF (10 ng/ml). At fixed times of exposure during 120 minutes, (1) superoxide production, (2) CD11B receptor expression, and (3) PMN adhesion to unstimulated human umbilical vein endothelial cell cultures were assayed. RESULTS: PAF induced prompt changes in PMN priming (increased superoxide production after N-formyl-methyl-leucyl-phenylalanine activation), adhesion to unstimulated endothelial cells, and CD11B receptor expression. Priming was temporally concordant with the rise and fall of CD11B expression but appeared to precede adhesion. CD11B blockade (F(Ab') 2 anti-CD11B [60.1] antibodies), before or at maximal PAF priming, reduced PMN adhesion but had no effect on superoxide production. CONCLUSIONS: In summary, PAF-induced PMN priming occurs in temporal concordance with the expression of CD11B and subsequent endothelial cell adherence, but CD11B-mediated adherence is not essential for this process.


Asunto(s)
Antígeno de Macrófago-1/fisiología , Neutrófilos/efectos de los fármacos , Factor de Activación Plaquetaria/farmacología , Adhesión Celular , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Humanos , Antígeno de Macrófago-1/análisis , Neutrófilos/fisiología
15.
Surgery ; 114(3): 624-8, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8367822

RESUMEN

Thoracic aortic disruptions after blunt trauma are highly lethal injuries. Diagnosis of these injuries has traditionally been based on clinical suspicion, chest radiographs, and aortography. The roles of dynamic computed tomography and transesophageal echocardiography are currently under investigation. Intravascular ultrasonography is a new technology with potential as a diagnostic adjunct in the evaluation of these injuries. We present a case of traumatic aortic disruption identified by intravascular ultrasonography after nondiagnostic aortography and dynamic computed tomography studies.


Asunto(s)
Accidentes de Tránsito , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/lesiones , Heridas no Penetrantes/diagnóstico por imagen , Adulto , Aortografía , Hemorragia/diagnóstico , Hemorragia/etiología , Humanos , Masculino , Tomografía Computarizada por Rayos X , Ultrasonografía , Heridas no Penetrantes/cirugía
16.
Arch Surg ; 127(8): 893-7; discussion 897-8, 1992 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1642532

RESUMEN

Gut bacteria translocation has been invoked as a prime cause of early postinjury death. To examine this hypothesis, we obtained emergency department blood cultures in 132 acutely injured patients requiring urgent laparotomy for trauma. In the latter half of these patients, mesenteric lymph node and liver biopsy cultures were also performed. The incidence of early bacteremia was 11% (10/94) in the patients without shock compared with 32% (12/38) in the group with shock. The majority (73%) were gram-positive bacteremias. Most notably, Staphylococcus was isolated in 13% (5/38) of the patients with shock, but these isolates were of no apparent clinical significance. In contrast, 18% (7/38) of the patients with shock had enteric bacteremias, and all of these patients died. Cultures were positive in 11% of the liver samples and 15% of the mesenteric lymph nodes. With the exception of two patients with concurrent enteric bacteremias, these hepatic and mesenteric lymph node bacteria were of no clinical significance. In conclusion, bacterial translocation occurs infrequently, and virtually all enteric bacteria were found in dying patients; the cause or effect remains to be defined.


Asunto(s)
Bacteriemia/epidemiología , Choque Traumático/etiología , Adulto , Bacteriemia/microbiología , Humanos , Incidencia , Hígado/microbiología , Hígado/patología , Estudios Prospectivos , Choque Hemorrágico/etiología , Choque Traumático/complicaciones , Choque Traumático/mortalidad , Tasa de Supervivencia
17.
Arch Surg ; 128(7): 746-50; discussion 750-2, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8317955

RESUMEN

OBJECTIVE: Emergency repair of the torn descending thoracic aorta has been associated with an almost 15% incidence of paraplegia. The literature to date suggests that the incidence of paraplegia is not influenced by mechanical adjuncts to enhance distal aortic perfusion during cross-clamping and therefore, "clamp and sew" has been considered an acceptable technique. The purpose of the present study was to review our experience with repair of descending thoracic aortas using partial left heart bypass and to compare this favorable initial experience with the available data on the use of the heparinless centrifugal pump. DESIGN: A retrospective review of the routine use of partial left heart bypass in 16 consecutive patients with descending thoracic aorta disruptions. Results were compared with similar reports in the recent literature on trauma. SETTING: A level 1 trauma facility in the Denver, Colo, metropolitan area. PATIENTS: All patients with multisystem blunt trauma with a mean injury severity score of 36. INTERVENTION: Repair of the descending thoracic aorta disruption using partial left heart bypass with a heparinless centrifugal pump. MAIN OUTCOME MEASURES: Primary outcome measures were survival and paraplegia; other monitored variables included proximal and distal aortic pressure, flow rates, and oxygen transport. RESULTS: Among the 14 survivors (88%) there were no cases of paraplegia, and intraoperative hemodynamics and oxygen transport were well maintained with partial left heart bypass. This experience is added to the available reported data on the use of the centrifugal pump. In these additional 42 patients, the mortality rate was 7%, with no incidence of paraplegia. CONCLUSIONS: This collective experience failed to disclose a single case of paraplegia when partial left heart bypass was employed for repair of descending thoracic aorta. Moreover, the use of partial left heart bypass in this cohort of critically injured patients is associated with survival and perioperative morbidity rates comparable with the best recent reports of emergency thoracic aortic repair.


Asunto(s)
Aorta Torácica/lesiones , Paraplejía/prevención & control , Complicaciones Posoperatorias/prevención & control , Heridas no Penetrantes/cirugía , Traumatismos Abdominales , Adulto , Puente Cardiopulmonar/métodos , Traumatismos Craneocerebrales , Urgencias Médicas , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Traumatismo Múltiple , Estudios Retrospectivos , Tasa de Supervivencia , Heridas no Penetrantes/mortalidad
18.
Arch Surg ; 129(1): 39-45, 1994 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8279939

RESUMEN

OBJECTIVE: To find a predictive model for postinjury multiple organ failure (MOF). DESIGN: A 3-year cohort study ending December 1992 (first year: retrospective; last 2 years: prospective). SETTING: Denver General Hospital (Colo) is a regional level I trauma center. PATIENTS: Consecutive trauma patients with an Injury Severity Score (ISS) greater than 15, with an age greater than 16 years, and who survived longer than 24 hours. Stepwise logistic regression analysis was performed in all patients (n = 394), in the subgroup of patients with 0 to 12 hours, plus 12 to 24 hours base deficit (BD) results (n = 220), and in a second subgroup of patients with BD plus lactate results at 0 to 12 hours and 12 to 24 hours (n = 106). MAIN OUTCOME: Postinjury MOF. RESULTS: The following variables were identified as independent predictors of MOF in the analysis of all patients: age more than 55 years, ISS greater than or equal to 25, and more than 6 U of red blood cells in the first 12 hours after admission (U RBC/12 hours). In the subgroup with BD results, the same analysis identified age greater than 55 years, greater than 6 U RBC/12 hours, and BD greater than 8 mEq/L (0 to 12 hours), while in the last subgroup analysis including BD and lactate results, greater than 6 U RBC/12 hours, BD greater than 8 mEq/L (0 to 12 hours), and lactate greater than 2.5 mmol/L (12 to 24 hours) were independently associated with MOF. CONCLUSIONS: Age greater than 55 years, ISS greater than or equal to 25, and greater than 6 U RBC/12 hours are early independent predictors of MOF. Subgroup analyses indicate that BD and lactate levels may add substantial predictive value. Moreover, these results emphasize the predominant role of the initial insult in the pathogenesis of postinjury MOF.


Asunto(s)
Insuficiencia Multiorgánica/epidemiología , Heridas y Lesiones/complicaciones , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Cohortes , Transfusión de Eritrocitos , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Factores de Riesgo
19.
Am J Surg ; 164(5): 501-5, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1443377

RESUMEN

Flexible fiberoptic bronchoscopy (FFB) to remove mucous plugs followed by selective intrabronchial air insufflation (SII) to expand the atelectatic lung was used in 17 surgical intensive care unit (SICU) patients with pulmonary lobar collapse. Thirteen patients were admitted for acute trauma, and the remainder were elderly postoperative patients. Lobar collapses occurred on SICU days 1 to 18 (mean +/- SEM: 5 +/- 1 days), and duration ranged from 4 to 258 hours (mean: 77 +/- 18 hours). Indications for FFB with SII included critical hypoxemia in 5 patients, worsening collapse in 2, and failure to respond to aggressive respiratory care in 10 (59%). FFB with SII was effective in 14 (82%) patients: 10 achieved full lung re-expansion, and 4 partial lung re-expansion. When lobar collapse was of less than 72 hours' duration, 92% (12 of 13) of patients had lungs re-expanded compared with 50% (2 of 4) whose collapse existed for more than 72 hours. The mean PaO2/FIO2 (fraction inspired oxygen) ratio was 135 +/- 18 prior to FFB with SII and increased to 205 +/- 21 after FFB with SII. Complications were minor and clinically insignificant. In conclusion, SII appears to be a simple, safe, effective adjunct to FFB in the treatment of SICU patients with pulmonary lobar collapse.


Asunto(s)
Insuflación , Oxígeno/uso terapéutico , Atelectasia Pulmonar/terapia , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bronquios , Broncoscopía , Niño , Protocolos Clínicos , Cuidados Críticos , Expectorantes/uso terapéutico , Femenino , Tecnología de Fibra Óptica , Humanos , Insuflación/métodos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Oxígeno/administración & dosificación , Estudios Prospectivos , Atelectasia Pulmonar/tratamiento farmacológico , Succión , Irrigación Terapéutica
20.
Am J Surg ; 166(6): 606-10; discussion 610-1, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8273837

RESUMEN

Recent studies have shown that selective gut decontamination can reduce the incidence of pneumonia, but this does not decrease multiple organ failure (MOF) or mortality. These findings have prompted the hypothesis that pneumonia is an inconsequential symptom of MOF. To test this, we prospectively evaluated 123 high-risk trauma patients (mean Injury Severity Score = 36.2 +/- 1.5). Organ dysfunction, scored daily according to a 12-point scale, ultimately developed in 28 (23%) patients. Major infections were diagnosed, based on strict criteria, in 59 patients (48%), and pneumonia developed in 52 patients (43%). Pneumonia was significantly associated with MOF (82% of patients with MOF versus 30% of patients without MOF, p < 0.0001). In 14 (50%) of the patients with MOF, pneumonia preceded a significant rise (greater than or equal to 3) in serial MOF scoring. Of note, 10 (71%) of these patients died. Among the remaining 14 patients with MOF, 10 developed pneumonia, but this was associated with a minimal increase (less than or equal to 2) in MOF scoring (3 patients died). These data, by temporal association with MOF scoring, implicate pneumonia in precipitating or significantly worsening organ failure in 50% of the patients who developed MOF.


Asunto(s)
Insuficiencia Multiorgánica/etiología , Neumonía/etiología , Heridas y Lesiones/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/complicaciones , Neumonía/complicaciones , Neumonía/mortalidad , Estudios Prospectivos , Factores de Tiempo , Heridas y Lesiones/mortalidad
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