RESUMEN
INTRODUCTION: The COVID-19 pandemic resulted in reconfiguration of the NHS. Elective services were stopped and trauma services focused on decreasing patient-clinician interactions and managing injuries nonoperatively wherever possible. The everyday life of the general public changed dramatically with the introduction of a national lockdown to prevent the spread of COVID-19. This paper looks at the experience of a South West London trauma unit. MATERIALS AND METHODS: All patients reviewed in fracture clinic and by the orthopaedic on-call team between 23 March to 23 April 2020 were included. Data on the mechanism of injury and whether this was a usual activity, the injury sustained and its management were collected. RESULTS: A total of 167 trauma injuries were seen, compared with 735 new patients with injuries in the previous month. The number of trauma operations completed decreased by 38%; 55% of injuries occurred inside the home and 44% outside the home during daily exercise. Some 31% of injuries were secondary to a new activity taken up during lockdown. Three open fractures and two polytrauma cases were seen that would have normally been managed at the local major trauma centre. CONCLUSION: Overall, both the number of injuries seen and trauma operations completed during the enforced lockdown decreased. This is probably due to a change in the way the general public are living their lives, and the reconfigurations within the NHS in response to the COVID-19 pandemic. This is an interesting time within trauma and orthopaedic departments, as they continue to adapt to the changing injuries and working environment.
Asunto(s)
Accidentes Domésticos/estadística & datos numéricos , Ejercicio Físico , Fracturas Óseas/epidemiología , Centros Traumatológicos , Accidentes por Caídas/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ciclismo/lesiones , COVID-19/prevención & control , Niño , Preescolar , Control de Enfermedades Transmisibles , Femenino , Fracturas del Cuello Femoral/epidemiología , Fracturas del Cuello Femoral/etiología , Fracturas del Cuello Femoral/cirugía , Fijación Interna de Fracturas , Fracturas Óseas/etiología , Fracturas Óseas/cirugía , Jardinería , Humanos , Lactante , Londres/epidemiología , Masculino , Persona de Mediana Edad , Fracturas del Radio/epidemiología , Fracturas del Radio/etiología , Fracturas del Radio/cirugía , SARS-CoV-2 , Adulto JovenRESUMEN
Gibberellins (GAs) control many aspects of plant development, including seed germination, shoot growth, flower induction and growth and fruit expansion. Leaf explants of Solanum nigrum (Black Nightshade; Solanaceae) were used for Agrobacterium-mediated delivery of GA-biosynthetic genes to determine the influence of their encoded enzymes on the production of bioactive GAs and plant stature in this species. Constructs were prepared containing the neomycin phosphotransferase (nptII) gene for kanamycin resistance as a selectable marker, and the GA-biosynthetic genes, their expression under the control of the CaMV 35S promoter. The GA-biosynthetic genes comprised AtGA20ox1, isolated from Arabidopsis thaliana, the product from which catalyses the formation of C(19)-GAs, and MmGA3ox1 and MmGA3ox2, isolated from Marah macrocarpus, which encode functionally different GA 3-oxidases that convert C(19)-GAs to biologically active forms. Increase in stature was observed in plants transformed with AtGA20ox1, MmGA3ox2 and MmGA3ox1 + MmGA3ox2, their presence and expression being confirmed by PCR and RT-PCR, respectively, accompanied by an increase in GA(1) content. Interestingly, MmGA3ox1 alone did not induce a sustained increase in plant height, probably because of only a marginal increase in bioactive GA(1) content in the transformed plants. The results are discussed in the context of regulating plant stature, since this strategy would decrease the use of chemicals to promote plant growth.
Asunto(s)
Giberelinas/biosíntesis , Oxigenasas de Función Mixta/metabolismo , Solanum nigrum/metabolismo , Arabidopsis/enzimología , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Oxigenasas de Función Mixta/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Regiones Promotoras Genéticas , Solanum nigrum/genética , Transformación GenéticaRESUMEN
There is little written about the value of revision surgery on lower-limb amputations. We report on 71 revision amputation procedures performed by a single surgeon in this retrospective analysis. The majority of our revisions (61%) were in amputees who had suffered trauma. We judged success from a surgical and a rehabilitation perspective using scoring systems. Revisions for bony and soft-tissue pathology had good outcomes from a surgical (85% and 82%) and a rehabilitation perspective. Revisions for infection had satisfactory results from a surgical perspective (73%) but less so from a rehabilitation perspective (25%). The results of the revisions for pain were poor showing surgical success only 50% of the time where a neuroma was suspected and only 25% when there was no apparent cause. There was little or no improvement in rehabilitation in both the pain groups. Revision surgery for certain pathologies gives a good surgical outcome and can improve pain and mobility status. Patient selection for surgery is key and evaluation by a multidisciplinary team is recommended.
Asunto(s)
Amputación Quirúrgica/rehabilitación , Extremidad Inferior/cirugía , Dolor Postoperatorio/rehabilitación , Procedimientos Innecesarios/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/estadística & datos numéricos , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Reoperación/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Reino Unido , Adulto JovenRESUMEN
In 1996 the quality of the early management of 100 consecutive patients referred to the SW Thames regional pelvic and acetabular unit between 1989 and 1992 was studied. The management of these patients was assessed in four specific areas, and guidelines were laid down. It was found that in 56% of patients the early management did not meet these suggested standards, with 34% having deficiencies in more than one area. These results were presented and published. Five years later, the early management of a further 100 consecutive referrals was assessed using these same guidelines, in order to close the audit loop. The treatment of 57% of patients still did not reach the guideline standards, but the number with problems in more than one area fell to 20%. There has been improvement in the early management of pelvic and acetabular injuries. The use of external fixation in cases of severe haemorrhage increased, but frames were often poorly applied. Early communication with the specialist centre was encouraged but unfortunately there was still an unacceptable delay in referral. The frequency of delayed referral actually increased during the 5 years between study groups.
Asunto(s)
Acetábulo/lesiones , Fracturas Óseas/terapia , Huesos Pélvicos/lesiones , Calidad de la Atención de Salud , Centros Traumatológicos/normas , Acetábulo/diagnóstico por imagen , Competencia Clínica , Inglaterra , Fracturas Óseas/diagnóstico por imagen , Hospitales Públicos/normas , Humanos , Auditoría Médica , Huesos Pélvicos/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Derivación y Consulta/normas , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To assess the effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase (AChE) levels in normal dogs. ANIMALS: Nine adult mixed breed dogs weighing between 18 and 27 kg. PROCEDURES: Fifty micro L of 0.25% demecarium bromide were applied to one eye of each dog every 8 h for 6 days. Blood was analyzed for AChE levels prior to commencement of eye drops, and at 45 min, 1 h 45 min, 4 h 45 min, 1 day, 3 days, and 7 days following commencement of eye drops using a 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) reaction. RESULTS: Acetylcholinesterase levels declined over the first 24 h following commencement of demecarium administration in most dogs. This decline was highly variable and was statistically significant by 24 h. In some individuals AChE levels were suppressed to levels approaching clinical toxicity. By day 3 AChE levels had risen to levels above baseline in most dogs. CONCLUSIONS: Topical ocular application of demecarium causes transient suppression of systemic acetylcholinesterase levels in most dogs. Acetylcholinesterase levels generally do not fall to toxic levels, but may do so in certain individuals. Demecarium bromide eye drops generally do not cause AChE toxicity, but dogs receiving such therapy should be monitored for signs of AChE toxicity, and concomitant use of other AChE inhibitors should be avoided.
Asunto(s)
Acetilcolinesterasa/efectos de los fármacos , Compuestos de Amonio Cuaternario/farmacología , Acetilcolinesterasa/sangre , Administración Tópica , Animales , Perros , Soluciones Oftálmicas , Compuestos de Amonio Cuaternario/administración & dosificación , Valores de ReferenciaRESUMEN
OBJECTIVE: To determine effects of commonly used ophthalmic antibiotics on cellular morphologic characteristics and migration of canine corneal epithelium in cell culture. SAMPLE POPULATION: Corneal epithelial cells harvested from corneas of 12 euthanatized dogs and propagated in cell culture. PROCEDURE: Cells were treated with various antibiotics after a defect was created in the monolayer. Cellular morphologic characteristics and closure of the defect were compared between antibiotic-treated and control cells. RESULTS: Cells treated with ciprofloxacin and cefazolin had the greatest degree of rounding, shrinkage, and detachment from plates. Cells treated with neomycin-polymyxin B-gramicidin and gentamicin sulfate had rounding and shrinkage but with less detachment. Cells treated with tobramycin and chloramphenicol grew similarly to control cells. On the basis of comparisons of defect circumference between control cells and cells exposed to antibiotics, tobramycin affected cellular migration the least. CONCLUSIONS AND CLINICAL RELEVANCE: Effects of ciprofloxacin and cefazolin on morphologic characteristics of canine corneal epithelial cells in vitro should be taken into consideration before using these antibiotics for first-line of treatment for noninfected ulcers. Of the antibiotics tested that have a primarily gram-negative spectrum of coverage, gentamicin inhibited corneal epithelial cell migration and had greater cytopathologic effects than tobramycin did. For antibiotics with a gram-positive coverage, chloramphenicol had no cytopathologic effects on cells in comparison to cefazolin, which caused most of the cells to shrink and detach from the plate. Polymyxin B-neomycin-gramicidin was midrange in its effects on cellular morphologic characteristics and migration.
Asunto(s)
Antibacterianos/farmacología , Movimiento Celular/efectos de los fármacos , Córnea/efectos de los fármacos , Perros/fisiología , Animales , Antiinfecciosos/farmacología , Cefazolina/farmacología , Cefalosporinas/farmacología , Cloranfenicol/farmacología , Ciprofloxacina/farmacología , Córnea/citología , Técnicas de Cultivo , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Gentamicinas/farmacología , Estadísticas no Paramétricas , Tobramicina/farmacologíaRESUMEN
OBJECTIVE: To determine aqueous humor flow rate in clinically normal dogs, using fluorophotometry. ANIMALS: 20 clinically normal Beagles. PROCEDURE: A study was performed on 5 dogs to establish an optimal protocol for fluorophotometric determination of aqueous humor flow rate. This protocol then was used to measure aqueous humor flow rate in 15 dogs. Corneas were loaded with fluorescein by topical application, and corneal and aqueous humor fluorescein concentrations were measured 5, 6.5, and 8 hours after application. Concentration-versus-time plots were generated, and slopes and ratios of the fluorescein concentration in the cornea and aqueous humor from these graphs were used to calculate flow rates. Calculations were performed by use of automated software provided with the fluorophotometer and by manual computation, and the 2 calculation methods were compared. RESULTS: The protocol established for the 5 dogs resulted in semilogarithmic and parallel decay of corneal and aqueous humor concentrations. Manually calculated mean +/- SD aqueous humor flow rates for left, right, and both eyes were 5.58 +/- 2.42, 4.86 +/- 2.49, and 5.22 +/- 1.87 microl/min, respectively, whereas corresponding flow rates calculated by use of the automated software were 4.54 +/- 3.08, 4.54 +/- 3.10, and 4.54 +/- 2.57 microl/min, respectively. Values for the left eye were significantly different between the 2 computation methods. CONCLUSIONS AND CLINICAL RELEVANCE: Aqueous humor flow rates can be determined in dogs, using fluorophotometry. This technique can be used to assess pathologic states and medical and surgical treatments that alter aqueous humor dynamics.
Asunto(s)
Humor Acuoso/fisiología , Perros/fisiología , Fluorofotometría/veterinaria , Animales , Ojo/metabolismo , Fluorofotometría/métodos , Modelos BiológicosRESUMEN
OBJECTIVE: To evaluate effects of topical application of a 2% solution of dorzolamide on intraocular pressure (IOP) and aqueous humor flow rate in clinically normal dogs. ANIMALS: 15 Beagles. PROCEDURE: The IOP was measured in both eyes of all dogs for 3 days to determine baseline values. In a single-dose study, 50 microl of dorzolamide or control solution was applied in both eyes at 7:00 AM, and IOP was measured 7 times/d. In a multiple-dose study, dorzolamide or control solution was applied to both eyes 3 times/d for 6 days, and IOP was measured 4 times/d during treatment and for 5 days after cessation of treatment. Aqueous humor flow rate was measured for all dogs fluorophotometrically prior to treatment and during the multiple-dose study. RESULTS: In the single-dose study, dorzolamide significantly decreased IOP from 30 minutes to 6 hours after treatment. Mean decrease in IOP during this time span was 3.1 mm Hg (18.2%). Maximal decrease was detected 6 hours after treatment (3.8 mm Hg, 22.5%). In the multiple-dose study, dorzolamide decreased IOP at all time points, and maximal decrease was detected 3 hours after treatment (4.1 mm Hg, 24.3%). Mean aqueous humor flow rate decreased from 5.9 to 3.4 microl/min (43%) after treatment in the dorzolamide group. CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of a 2% solution of dorzolamide significantly decreases IOP and aqueous humor flow rate in clinically normal dogs. Therefore, topical administration of dorzolamide should be considered for the medical management of dogs with glaucoma.
Asunto(s)
Humor Acuoso/efectos de los fármacos , Inhibidores de Anhidrasa Carbónica/farmacología , Perros/fisiología , Presión Intraocular/efectos de los fármacos , Sulfonamidas/farmacología , Tiofenos/farmacología , Administración Tópica , Animales , Humor Acuoso/fisiología , Inhibidores de Anhidrasa Carbónica/administración & dosificación , Femenino , Fluorofotometría/veterinaria , Glaucoma/tratamiento farmacológico , Glaucoma/veterinaria , Presión Intraocular/fisiología , Masculino , Distribución Aleatoria , Sulfonamidas/administración & dosificación , Tiofenos/administración & dosificaciónRESUMEN
The gibberellin (GA) 20-oxidase (CmGA20ox1) from immature pumpkin seed produces predominantly inactive tricarboxylic acid GAs. We expressed CmGA20ox1 under the control of the CaMV 35S promoter in Solanum dulcamara to assess the usefulness of this gene for reducing GA content in transgenic plants. All transgenic plants obtained were semi-dwarfs with smaller, deep-green leaves and highly pigmented stems compared to the wild-type. Such transformants flowered earlier than the wild-type plants and produced more fruit and more seeds per fruit. The transgene was efficiently expressed, producing high levels of CmGA20ox1 transcript and protein. Furthermore, the concentration of GA(1) was reduced in leaves of the transformants to approximately 20% or less of that in the wild-type and to about 40% or less in stems. The concentrations of other 13-hydroxylated GAs were also reduced, except for the tricarboxylic acid, GA(17), which accumulated in the transformants due to 13-hydroxylation of GA(25). By contrast, the concentrations of non-13-hydroxylated GAs, GA(4) and GA(34), were not consistently reduced, indicating that the effect of expressing the pumpkin gene may not be predictable. Transcript abundance for a native GA 20-oxidase gene was higher in the leaves and stems of S. dulcamara transformed with the pumpkin gene than in wild-type, reflecting the feedback control of 20-oxidase gene expression that serves as a homeostatic mechanism for GAs.
Asunto(s)
Oxigenasas de Función Mixta/genética , Solanaceae/crecimiento & desarrollo , Secuencia de Bases , Cartilla de ADN , ADN Complementario , Plantas Modificadas Genéticamente , Deportes de Raqueta , Solanaceae/enzimología , Solanaceae/genéticaRESUMEN
The migration of uncemented press-fit CLS (Cementless Total Hip Replacement System) acetabular cups was measured retrospectively from standard anteroposterior pelvic radiographs using a digitizer and software specifically developed for this study. A radiographic and clinical review also were undertaken. There were 96 patients in the study group. The mean follow-up for radiographic review was 2.23 years, and the mean follow-up for clinical review was 3 years. Migration was measured in the cranial and medial directions. Mean migration of the cup at 2 years was 1.35 mm in the cranial direction and 2.15 mm in the medial direction. Radiographic appearances altered little over the study period. Fifty-five (57.3%) patients demonstrated bone ingrowth onto the prosthesis, predominantly in DeLee and Charnley zone 1. Twenty-one patients demonstrated nonprogressive sclerotic lines; no lucent lines were encountered. Statistical analysis showed a significant correlation between acetabular ingrowth and reduced cup migration in the medial direction (P = .011 at 5 years). There was no statistical relationship between migration of the cup and radiographic features or clinical outcome.
Asunto(s)
Acetábulo , Artroplastia de Reemplazo de Cadera/efectos adversos , Migración de Cuerpo Extraño/diagnóstico por imagen , Migración de Cuerpo Extraño/etiología , Falla de Prótesis , Adulto , Anciano , Artroplastia de Reemplazo de Cadera/instrumentación , Cementos para Huesos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Oseointegración , Diseño de Prótesis , Radiografía , Estudios Retrospectivos , Factores de TiempoRESUMEN
The migration of uncemented CLS (Cementless Total Hip Replacement System) femoral stems was measured retrospectively from standard anteroposterior pelvic radiographs using a digitizer and software specifically designed for this study. The study population was comprised of 117 patients with 126 uncemented CLS femoral stems. All radiographs were reviewed and the incidence of thigh pain obtained by means of a questionnaire. The mean clinical follow-up was 3 years and the mean follow-up for radiographic review was 2.77 years. The mean femoral stem migration was 2 mm at 2 years and 3.66 mm at 7 years. Radiographic features varied little with no specific predictive features in patients with excessive early migration or those who complained of thigh pain. There was no statistical relationship between the presence of thigh pain and femoral stem migration.
Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Fémur , Migración de Cuerpo Extraño/diagnóstico por imagen , Migración de Cuerpo Extraño/etiología , Falla de Prótesis , Adulto , Anciano , Artroplastia de Reemplazo de Cadera/instrumentación , Cementos para Huesos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/etiología , Valor Predictivo de las Pruebas , Diseño de Prótesis , Radiografía , Estudios Retrospectivos , Muslo , Factores de TiempoRESUMEN
Soluble enzyme preparations from embryos and endosperm of Marah macrocarpus (previously Echinocystis macrocarpa) were incubated with [14C4]gibberellin(GA)12-aldehyde, [14C4]GA12, [14C1] GA9, 2,3-didehydro[14C1]GA9, [14C1]GA20, and [17-13C, 3H]GA5. Embryo preparations converted GA12-aldehyde, GA12, and GA9 to GA4 and GA7; 2,3-didehydroGA9 to GA7; GA5 to GA3; and GA20 (incompletely) to GA1 and GA60, but not to GA3. Endosperm preparations converted GA12-aldehyde and GA12 to GA15, GA24, and GA9, but, unlike embryo preparations, not to GA4 or GA7. However, GA4 and GA7 were formed from GA9 and GA7 was formed from 2,3-didehydroGA9. Metabolism of GA5 to GA3 and GA20 to GA1 was low. 2,3-DidehydroGA9 accumulated when GA9 was incubated with a desalted endosperm preparation. A cDNA clone (M3-8), selected from an embryo-derived cDNA library using a DNA fragment generated by reverse transcriptase polymerase chain reaction, was expressed in Escherichia coli. The fusion protein converted GA12 to GA9 (major) and GA25 (minor); GA53 was metabolized less effectively and only to GA44. Thus, the M3-8 protein is functionally similar to GA 20-oxidases from Arabidopsis thaliana, Spinacia oleracea, and Pisum sativum, but different from that from Cucurbita maxima seeds, to which its amino acid sequence is most closely related. mRNA hybridizing to M3-8 accumulated in embryos and endosperm of M. macrocarpus, but was absent in vegetative tissues.
Asunto(s)
Giberelinas/metabolismo , Oxigenasas de Función Mixta/metabolismo , Plantas/metabolismo , Secuencia de Aminoácidos , Clonación Molecular , ADN Complementario , Escherichia coli , Biblioteca de Genes , Oxigenasas de Función Mixta/biosíntesis , Oxigenasas de Función Mixta/química , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Semillas/metabolismo , Homología de Secuencia de Aminoácido , Especificidad por SustratoRESUMEN
PCR was used with degenerate primers based on conserved amino acid sequences in gibberellin (GA) 20-oxidases to isolate cDNA clones for these enzymes from young seeds of pea (Pisum sativum) and developing embryos of French bean (Phaseolus vulgaris). One GA 20-oxidase cDNA (Ps27-12) was obtained from pea and three (Pv 15-11, Pv73-1 and Pv85-26) from bean. Their identities were confirmed by demonstrating that fusion proteins expressed in Escherichia coli exhibited GA 20-oxidase activity, converting [14C]GA12 to [14C]GA9. The intermediates in this three-step reaction, GA15 and GA24, were also identified as products. The expression proteins from three of the clones (Ps27-12, Pv15-11 and Pv73-1) were also shown to convert GA53 to GA20, as effectively as they did GA12. On the basis of transcript levels measured by northern blot analysis, the pea GA 20-oxidase gene is most highly expressed in young leaves, fully expanded internodes, very young seeds (until 4 days after anthesis) and expanding pods (from 3 days after anthesis at least until day 6). Expression in pods from 3-day-old unpollinated ovaries is higher than in those from pollinated ovaries. Treatment of unpollinated ovaries with GA3 to induce parthenocarpic fruit-set severely reduced the amount of GA 20-oxidase mRNA, whereas treatment with 2,4-D, although inducing fruit-set, did not reduce the levels of these transcripts. Plant decapitation above an unpollinated ovary resulted in very high levels of GA 20-oxidase mRNA in the pod. The three GA 20-oxidase genes from French bean showed very different patterns of expression: Pv 15-1 was expressed in the roots, young leaves, and developing seeds, but most highly in immature cotyledons, while Pv73-1 has a similar expression pattern to Ps27-12, with transcripts found only in young seeds and young leaves, where it was particularly abundant. Transcripts corresponding to Pv85-26 were detected in developing seeds, and just traces in the young leaves. Southern blot analysis indicated that the bean GA 20-oxidases are each encoded by single-copy genes, whereas one more gene, homologous to Ps27-12, could also exist in pea.
Asunto(s)
Fabaceae/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Oxigenasas de Función Mixta/genética , Pisum sativum/genética , Plantas Medicinales , Secuencia de Aminoácidos , Clonación Molecular , ADN de Plantas/análisis , Escherichia coli/genética , Fabaceae/crecimiento & desarrollo , Dosificación de Gen , Genes de Plantas/genética , Giberelinas/biosíntesis , Datos de Secuencia Molecular , Pisum sativum/crecimiento & desarrollo , Filogenia , ARN Mensajero/análisis , ARN de Planta/análisis , Proteínas Recombinantes , Semillas/química , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
An Abyssinian cat presented with epistaxis, melaena and retinal vascular changes. Plasma protein levels were markedly elevated and a monoclonal gammopathy was present on serum protein electrophoresis. Based on these laboratory findings, hyperviscosity syndrome was assumed to be responsible for the clinical signs. The cat responded initially to fluid therapy, but relapsed and then developed unilateral exophthalmia. The animal was euthanased and an extramedullary plasmacytoma of the right orbit was diagnosed at postmortem examination.
Asunto(s)
Enfermedades de los Gatos/patología , Neoplasias Orbitales/veterinaria , Plasmacitoma/veterinaria , Animales , Autopsia/veterinaria , Proteínas Sanguíneas/análisis , Médula Ósea/patología , Enfermedades de los Gatos/sangre , Enfermedades de los Gatos/diagnóstico , Gatos , Fluidoterapia/veterinaria , Inmunoglobulina M/sangre , Masculino , Neoplasias Orbitales/diagnóstico , Neoplasias Orbitales/patología , Paraproteinemias/sangre , Paraproteinemias/veterinaria , Células Plasmáticas/patología , Plasmacitoma/diagnóstico , Plasmacitoma/patologíaRESUMEN
Enzyme replacement is a potential therapy for mucopolysaccharidosis I (MPS I), a lysosomal storage disorder caused by alpha-L-iduronidase deficiency. Previous work showed improvement in the tissues of MPS I dogs treated intravenously for 3 months with recombinant human alpha-L-iduronidase (25,000 units or approximately 0.1 mg/kg/week). We have now treated an MPS I-affected dog for 13 months to assess the clinical effects of enzyme replacement. The treated dog gained more weight, was more active, and had less joint stiffness than the untreated littermate. Biochemical and histologic studies demonstrated uptake of alpha-L-iduronidase and decreased lysosomal storage in the liver, kidney, spleen, lymph nodes, synovium, adrenals, and lungs. The brain had detectable enzyme activity and decreased glycosaminoglycan storage although histologic improvement was not evident. Cartilage and heart valve did not show any detectable improvement. A fivefold higher dose (approximately 0.5 mg/kg) administered five times over 10 days to two other dogs resulted in higher tissue enzyme activity and similarly decreased glycosaminoglycan storage and excretion. Antibodies to human alpha-L-iduronidase were induced in all treated dogs and may be associated with immune complex deposition and proteinuria. Recombinant canine alpha-L-iduronidase also induced antibody formation to a similar degree. The results support the conclusion that enzyme replacement is a promising therapy for MPS I though immunologic complications may occur.
Asunto(s)
Iduronidasa/uso terapéutico , Mucopolisacaridosis I/tratamiento farmacológico , Animales , Formación de Anticuerpos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Química Encefálica , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Iduronidasa/metabolismo , Iduronidasa/farmacología , Lisosomas/metabolismo , Lisosomas/patología , Masculino , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Distribución TisularRESUMEN
OBJECTIVE: To compare the relative efficacies of 4 topical nonsteroidal anti-inflammatory drugs at preventing blood-aqueous barrier (BAB) disruption in dogs. DESIGN: 1 eye of each dog was treated with 1% suspensions of diclofenac, flurbiprofen, suprofen, or tolmetin, or with control solution. After 4 applications of eyedrops at 10-minute intervals, BAB disruption was induced in the treated eye by anterior chamber paracentesis. The severity of BAB disruption was measured by anterior chamber fluorophotometry. ANIMALS: 40 ocular-normal dogs. PROCEDURE: After pretreatment with eyedrops, rapid 100-microliters nonleaking anterior chamber paracentesis was performed in 1 eye of each dog to induce BAB disruption. 1 day after paracentesis, 1 ml of 10% fluorescein sodium was injected i.v.. The amount of fluorescein entering the anterior chamber of each eye was measured 30 to 60 minutes later by use of a computerized scanning fluorophotometer. The degree of BAB disruption was determined by comparing the amount of fluorescein entering the aqueous humor of the paracentesed eye with that of the nonparacentesed eye. RESULTS: At postparacentesis day 1, the order of statistically significant BAB-stabilizing efficacy among groups was: diclofenac > flurbiprofen > suprofen > tolmetin = control solution. CONCLUSIONS: Topically applied 1% suspensions of diclofenac, flurbiprofen, and suprofen are effective at preventing BAB disruption after paracentesis in dogs, indicating their potential usefulness for treatment of prostaglandin-mediated ocular disease. 1% tolmetin is no more effective than control solution.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Barrera Hematoacuosa/efectos de los fármacos , Barrera Hematoacuosa/fisiología , Diclofenaco/farmacología , Perros/fisiología , Flurbiprofeno/farmacología , Suprofeno/farmacología , Tolmetina/farmacología , Animales , Cámara Anterior/metabolismo , Antiinflamatorios no Esteroideos/administración & dosificación , Diclofenaco/administración & dosificación , Perros/metabolismo , Ojo/metabolismo , Fluoresceína , Fluoresceínas/farmacocinética , Fluorofotometría/métodos , Fluorofotometría/veterinaria , Flurbiprofeno/administración & dosificación , Fenómenos Fisiológicos Oculares , Soluciones Oftálmicas , Distribución Aleatoria , Suprofeno/administración & dosificación , Tolmetina/administración & dosificaciónRESUMEN
One hundred consecutive referrals with pelvic and acetabular fractures treated over a three year period were reviewed with regard to their early management. Early management was subdivided into four areas: 1. initial assessment and treatment; 2. imaging; 3. referral; 4. management of associated injuries. The cases comprised 26 pelvic fractures (18 treated operatively), 69 acetabular fractures (50 treated operatively), and 5 combination fractures (3 treated operatively). Guidelines were laid down in each of the four areas of management and each patient's management was compared with this ideal. 56% of cases had deficient management by our criteria. There were important failures in diagnosis and early treatment of these complex injuries. A set of simple guidelines is offered to help improve the situation.
Asunto(s)
Fijación de Fractura/métodos , Fracturas Óseas/cirugía , Huesos Pélvicos/lesiones , Acetábulo/diagnóstico por imagen , Acetábulo/lesiones , Acetábulo/cirugía , Protocolos Clínicos , Fracturas Óseas/diagnóstico por imagen , Hemorragia/cirugía , Humanos , Masculino , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/cirugía , RadiografíaRESUMEN
OBJECTIVE: A series of studies examined how various blood ethanol concentrations influenced the effectiveness of a negative punishment procedure in a risk-taking/decision-making task. Based on the animal punishment literature plus the impression that ethanol diminishes the effects of punishment and impairs decision making, it was predicted that individuals receiving alcohol would increase their risk- taking behavior despite the presence of a negative punishment stimulus (point loss) given on a variable schedule. METHODS: In Experiment 1, a within-subjects design with repeated measures was used where 10 male subjects played a modified computer-generated choice game under three levels of punishment certainty, three levels of punishment severity and four ranges of blood ethanol (0.00%, 0.01-0.049%, 0.050-0.099%, 0.10-0.15%) RESULTS: Results indicated significant decreases in risk taking as either punishment certainty or severity was increased. However, no significant effects were found for ethanol, or interactions of ethanol with punishment certainty or punishment severity. Two additional studies examining aspects of the experimental procedure produced similar results CONCLUSIONS: Overall, the results of these studies do not support the hypothesis that high concentrations of blood alcohol are sufficient in and of themselves to eliminate the suppression function of negative punishment contingencies leading to increased risk-taking behavior. The implications of these results for understanding blood alcohol effects are discussed.
Asunto(s)
Intoxicación Alcohólica/psicología , Toma de Decisiones , Etanol/sangre , Motivación , Castigo , Adulto , Intoxicación Alcohólica/sangre , Conducta de Elección/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Asunción de RiesgosRESUMEN
Using degenerate oligonucleotide primers based on a pumpkin (Cucurbita maxima) gibberellin (GA) 20-oxidase sequence, six different fragments of dioxygenase genes were amplified by polymerase chain reaction from arabidopsis thaliana genomic DNA. One of these was used to isolate two different full-length cDNA clones, At2301 and At2353, from shoots of the GA-deficient Arabidopsis mutant ga1-2. A third, related clone, YAP169, was identified in the Database of Expressed Sequence Tags. The cDNA clones were expressed in Escherichia coli as fusion proteins, each of which oxidized GA12 at C-20 to GA15, GA24, and the C19 compound GA9, a precursor of bioactive GAs; the C20 tricarboxylic acid compound GA25 was formed as a minor product. The expression products also oxidized the 13-hydroxylated substrate GA53, but less effectively than GA12. The three cDNAs hybridized to mRNA species with tissue-specific patterns of accumulation, with At2301 being expressed in stems and inflorescences, At2353 in inflorescences and developing siliques, and YAP169 in siliques only. In the floral shoots of the ga1-2 mutant, transcript levels corresponding to each cDNA decreased dramatically after GA3 application, suggesting that GA biosynthesis may be controlled, at least in part, through down-regulation of the expression of the 20-oxidase genes.