RESUMEN
AIMS: To evaluate the success of a commercially available analgesic device (CoolSense; Coolsense Ltd, Tel Aviv, Israel) in ameliorating pain while sampling from subcutaneous tissue cages in sheep. METHODS: The CoolSense device was used as part of a major parent study involving repetitive percutaneous sampling of subcutaneous tissue cages in seven sheep. Sampling was performed by passing a hypodermic needle through the skin and withdrawing fluid from the tissue cage. Each sheep had 10 tissue cages that were individually sampled 14 times over 74 h. The device was placed on the skin of the sampling site immediately before sampling cooling and numbing the skin. The reaction of the sheep was observed by the operators, flinching or jumping as the needle was passed through the skin was deemed to be a failure. We recorded the success or failure of the device for each needle stick. This was opportunistic data collection as part of a pharmacokinetic trial, therefore no controls were included. RESULTS: A total of 1655 observations were recorded and then analysed using a generalised linear mixed model. Overall, 1380 of 1655 (83.4%) observations were recorded as successfully providing analgesia. Marked inter-occasion variability was noted with success ranging from 61.42% to 92.86% across sheep:period (approximately 140 observations each). As no controls were available, the effect of treatment could not be evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: The CoolSense device is a viable option for veterinary research and clinical applications.
Asunto(s)
Dolor , Animales , Dolor/veterinaria , OvinosRESUMEN
The primary goal of this pilot study was to assess, the efficacy of a new nutraceutical, 4CYTE™ Epiitalis® Forte, containing, as a standalone, a proprietary plant oil extract, Epiitalis, in dogs presenting with signs of osteoarthritis (OA). Fifty dogs aged 9.2 (±3.2) years with signs of naturally occurring OA were included in this report. They were free of other comorbidities and were not on any medications except for those utilised for managing their OA. In these dogs, the current treatments were continued to avoid any sudden changes in their disease management. The effects of the 4CYTE Epiitalis Forte were assessed both at the beginning and at the end of a 1 month-long treatment period. The evaluation consisted of an objective lameness assessment (TPI%[total pressure index]) using a gait analysis (GAITRite® Portable Walkway System) and a subjective quality-of-life questionnaire, the Helsinki Chronic Pain Index (HCPI). Additional exploratory objective measurements included the Symmetry Index (SI) and the fore/hind limb ratio (T/P TPI%). Of dogs, 74% (34/46) registered a numerical improvement in TPI% in their worse limb. In addition, of the 93.5% of the dogs that demonstrated improvement in their HCPI scores by at least 5% on the quality-of-life questionnaire, 79% demonstrated improvements in gait based on TPI%. Finally, there were improvements measured in both exploratory objective endpoints SI and T/P TPI%. These encouraging results will be used to develop a protocol for a follow-up placebo-controlled randomised study to confirm the efficacy of this new nutraceutical for dogs suffering from OA.
Asunto(s)
Enfermedades de los Perros , Osteoartritis , Animales , Suplementos Dietéticos , Perros , Marcha , Osteoartritis/veterinaria , Proyectos PilotoRESUMEN
Expressions are derived for additional contributions to the linear, quadratic, and cubic electric susceptibilities of molecular crystals that arise when molecules are displaced by the applied electric field. The contributions depend on quantities related to the infrared intensity of lattice vibrations, to the Raman intensity of lattice vibrations, and to the intensity of hyper-Rayleigh scattering. Some nonlinear contributions are zero except for response to a static electric field applied directly or produced by optical rectification. There are also contributions from averaging the susceptibilities in the equilibrium structure over the lattice modes.
RESUMEN
A microscopic theory is presented for piezoelectricity, electrostriction, and pyroelectricity in molecular crystals. The required coefficients are derived by combining a theoretical treatment of the dependence of molecular dipole moments on molecular displacement and a generalized elastic theory for internal strain.
RESUMEN
We present an n-fold way kinetic Monte Carlo simulation of the hopping motion of Li+ ions in polyethylene on a grid of mesh 0.36 A superimposed on the voids of the rigid polymer. The structure of the polymer is derived from a higher-order simulation, and the energy of the ion at each site is derived by the self-consistent polarization field method. The ion motion evolves in time from free flight through anomalous diffusion to normal diffusion, with the average energy tending to decrease with increasing temperature through thermal annealing. We compare the results with those of hopping models with probabilistic energy distributions of increasing complexity by analyzing the mean-square displacement and the average energy of an ensemble of ions. The Gumbel distribution describes the ion energy statistics in this system better than the usual Gaussian distribution does; including energy correlation greatly affects the ion dynamics. The analysis uses the standard data compression program GZIP, which proves to be a powerful tool for data analysis by giving a measure of recurrences in the ion path.
RESUMEN
Calculations for the crystalline energetic material RDX (1,3,5-trinitro-1,3,5-triazacyclohexane) yield the effective polarizability (17.2 angstroms3), local electric field tensor, effective dipole moment (9.40 D), and dipole-dipole energy (-27.2 kJ/mol). Fourier-transform techniques give the polarization energy P for a single charge in the perfect crystal as -1.14 eV; the charge-dipole energy W(D) is zero if the crystal carries no bulk dipole moment. Polarization energies for charge-transfer (CT) pairs combine with the Coulomb energy E(C) to give the screened Coulomb energy E(scr); screening is nearly isotropic with E(scr) approximately = E(C)2.6. For CT pairs W(D) reduces to a term deltaW(D) arising from the interaction of the charge on each ion with the change in dipole moment on the other ion relative to the neutral molecule. The dipole moments are calculated as 7.40 D for the neutral molecule and 6.84 D and 7.44 D for the anion and cation, giving the lowest two CT pairs at -1.34 eV and -0.94 eV. The changes in P and W(D) near a molecular vacancy yield traps with depths that reach 400 meV for single charges and 185 meV for the nearest-neighbor CT pair. Divacancies yield traps with depths nearly equal to the sum of those produced by the separate vacancies. These results are consistent with a mechanism in which detonation of RDX is initiated by mechanical generation of CT pairs that localize at vacancies, recombine, and release energy sufficient to break bonds; crystals of molecules with lower dipole moments should be less sensitive.
RESUMEN
Calculations for the acetanilide crystal yield the effective polarizability (16.6 A(3)), local electric field tensor, effective dipole moment (5.41 D), and dipole-dipole energy (-12.8 kJ/mol). Fourier-transform techniques are used to calculate the polarization energy P for a single charge in the perfect crystal (-1.16 eV); the charge-dipole energy W(D) is zero if the crystal carries no bulk dipole moment. Polarization energies for charge-transfer (CT) pairs combine with the Coulomb energy E(C) to give the screened Coulomb energy E(scr); screening is nearly isotropic, with E(scr) approximately E(C)/2.7. For CT pairs W(D) reduces to a term deltaW(D) arising from the interaction of the charge on each ion with the change in dipole moment on the other ion relative to the neutral molecule. The dipole moments calculated by density-functional theory methods with the B3LYP functional at the 6-311++G(**) level are 3.62 D for the neutral molecule, changing to 7.13 D and 4.38 D for the anion and cation, relative to the center of mass. Because of the large change in the anion, deltaW(D) reaches -0.9 eV and modifies the sequence of CT energies markedly from that of E(scr), giving the lowest two CT pairs at -1.98 eV and -1.41 eV. The changes in P and W(D) near a vacancy are calculated; W(D) changes for the individual charges because the vacancy removes a dipole moment and modifies the crystal dielectric response, but deltaW(D) and E(C) do not change. A vacancy yields a positive change DeltaP that scatters a charge or CT pair, but the change DeltaW(D) can be negative and large enough to outweigh DeltaP, yielding traps with depths that can exceed 150 meV for single charges and for CT pairs. Divacancies yield traps with depths nearly equal to the sum of those produced by the separate vacancies and so they can exceed 300 meV. These results are consistent with a mechanism of optical damage in which vacancies trap optically generated CT pairs that recombine and release energy; this can disrupt the lattice around the vacancy, thereby favoring trapping and recombination of CT pairs generated by subsequent photon absorption, leading to further lattice disruption. Revisions to previous calculations on trapping of CT pairs in anthracene are reported.
RESUMEN
Polarization energies are calculated for a single excess charge on a polyethylene chain in amorphous polyethylene using (i) local segment and nonlocal distributed molecular polarizabilities, (ii) material structures simulated by both general-purpose and specialist Monte Carlo software, and (iii) uniform and Gaussian distributions of charge with different extents of charge delocalization. Local and distributed response lead to results that are essentially the same except that they correspond to different mean polarizabilities. With increasing delocalization of the charge along the chain, the polarization energies shift to higher values and the width of their distribution decreases, the differences being more pronounced for the uniform distribution. The polarization energies for charges delocalized over 10-20 methylene units form a distribution some 14 eV wide centered around 1 eV, narrowing significantly for more homogeneous polymer melts. The calculations are relevant to trapping of charge in polyethylene. They also yield the microscopic variation in the potential along the polymer chain caused by the polarization energy difference, and so may provide useful inputs to theories of electronic conduction in polymer materials.
RESUMEN
Topological partitioning of electronic properties is used to investigate the polarizability of para-nitroaniline and meta-nitroaniline. The distributed polarizabilities for atoms are combined into total local or generalized distributed contributions for the amino, ring, and nitro functional groups; generalized distributed group contributions have not been calculated before. The local group contributions are transferable between the two molecules only when charge transfer is suppressed, but the generalized distributed contributions prove surprisingly similar in the two molecules, apparently because they treat charge-transfer contributions explicitly.
RESUMEN
The method of images is tested by comparing two ways of calculating the polarization energy in crystalline fullerene C60 and in bulk amorphous polyethylene (PE): (i) treating the whole molecular material microscopically, and (ii) replacing part of the material by a uniform dielectric continuum of the same relative permittivity. The method of images is accurate to within 5% once the distance of the charge from the surface of the dielectric continuum exceeds about twice the average spacing between the polarizable units in the molecular material. For C60 crystals the method of images always overestimates the magnitude of the polarization energy, partly because it ignores the reduction in the relative permittivity of the dielectric continuum near its surface. For amorphous PE the method of images can overestimate or underestimate the true result, depending on the local density around the charge.
RESUMEN
Mixing of chicken heterophils and Salmonella enterica serovar Typhimurium resulted in a rapid disappearance of heterophils when examined by scanning electron microscopy and trypan blue dye exclusion test. This disappearance appeared to be caused by a rapid degranulation of heterophils.
Asunto(s)
Degranulación de la Célula , Pollos/sangre , Granulocitos/fisiología , Salmonella enterica/fisiología , Animales , Quimiotaxis de Leucocito , Pollos/inmunología , Granulocitos/ultraestructura , Microscopía Electrónica de Rastreo/veterinariaRESUMEN
Neoplastic diseases associated with retroviruses were diagnosed in four Burmese pythons (Python molurus bivattatus) from a single collection. Snake No. 1 was a 7-year-old female with recurrent undifferentiated mesenchymal round cell tumor (lymphosarcoma) of the oral cavity. At necropsy, similar neoplastic masses were evident in the uterus and ovary, and there was diffuse involvement of the spleen. Snake No. 2 was a 4.5-year-old female that was euthanatized because of complications following resection of a segmental colonic adenocarcinoma. Snake No. 3 was a 5-year-old female that was euthanatized because of a large transitional cell carcinoma of the right kidney. Snake No. 4 was a 19-year-old female that was euthanatized following recurrence of an intermandibular fibrosarcoma. Ultrastructural examination revealed few to numerous extracellular and intracellular (intravacuolar) type C-like retroviral particles in all tumors. Tumors were about 90-95 nm in diameter, with an electron-dense core and bilaminar external membrane. The relationship of the intraneoplastic viral particles to the etiology of the tumors is uncertain.
Asunto(s)
Boidae , Neoplasias/veterinaria , Infecciones por Retroviridae/veterinaria , Retroviridae/aislamiento & purificación , Virión/aislamiento & purificación , Animales , Resultado Fatal , Femenino , Neoplasias/ultraestructura , Neoplasias/virología , Retroviridae/ultraestructura , Infecciones por Retroviridae/diagnóstico , Virión/ultraestructuraRESUMEN
Twenty feline vaccine-associated sarcomas were examined by transmission electron microscopy. Tumors contained pleomorphic spindle cells, histiocytoid cells, and giant cells. Most tumors contained myofibroblasts, which had morphologic features similar to those of fibroblasts. These cells were further distinguished by subplasmalemmal dense plaques and thin cytoplasmic actin myofilaments organized as elongated bundles concentrated at irregular intervals forming characteristic dense bodies. Intracellular crystalline particulate material was found in 5 of the 20 tumors. Energy dispersive X-ray spectroscopy was used to identify the crystalline material within one tumor as aluminum-based. One tumor from a feline leukemia virus-infected cat contained budding and immature retroviral particles.
Asunto(s)
Enfermedades de los Gatos/etiología , Enfermedades de los Gatos/patología , Fibrosarcoma/veterinaria , Vacunación/veterinaria , Vacunas/efectos adversos , Aluminio/análisis , Animales , Gatos , Fibroblastos/patología , Fibroblastos/ultraestructura , Fibrosarcoma/etiología , Fibrosarcoma/ultraestructura , Inmunohistoquímica/veterinaria , Microscopía Electrónica/veterinaria , Espectrometría por Rayos X/veterinaria , Vacunación/efectos adversosRESUMEN
OBJECTIVE: To characterize retroviruses isolated from boid snakes with inclusion body disease (IBD). ANIMALS: 2 boa constrictors with IBD and 1 boa exposed to an affected snake. PROCEDURE: Snakes were euthanatized, and tissue specimens and blood samples were submitted for virus isolation. Tissue specimens were cultured with or without commercially available viper heart cells and examined by use of transmission electron microscopy (TEM) for evidence of viral replication. Reverse transcriptase activ ty was determined in sucrose gradient-purified virus. Western blotting was performed, using polyclonal antibodies against 1 of the isolated viruses. Specificity of the rabbit anti-virus antibody was evaluated, using an immunogold-labeling TEM technique. RESULTS: 3 viruses (RV-1, RV-2, and RV-3) were isolated. The isolates were morphologically comparable to members of the Retroviridae family. Reverse transcriptase activity was high in sucrose gradient fractions that were rich in virus. Polyclonal antibody against RV-1 reacted with proteins of similar relative mobility in RV-1 and RV-2. By use of immunogold labeling, this antibody also recognized virions of both RV-1 and RV-2. CONCLUSIONS AND CLINICAL RELEVANCE: A retrovirus was isolated from boid snakes with IBD or exposed to IBD. Western blot analysis of viral proteins indicated that viruses isolated from the different snakes were similar. Whether this virus represents the causative agent of IBD is yet to be determined. The isolation of retroviruses from boid snakes with IBD is an important step n the process of identifying the causative agent of this disease.
Asunto(s)
Boidae/virología , Cuerpos de Inclusión Viral/virología , Infecciones por Retroviridae/veterinaria , Retroviridae/aislamiento & purificación , Animales , Anticuerpos Antivirales/análisis , Western Blotting/veterinaria , Células Cultivadas , Técnicas de Cultivo/veterinaria , Efecto Citopatogénico Viral , Inmunohistoquímica/veterinaria , Microscopía Electrónica/veterinaria , ADN Polimerasa Dirigida por ARN/metabolismo , Retroviridae/clasificación , Retroviridae/enzimología , Retroviridae/inmunología , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/virologíaRESUMEN
The anti-idiotype monoclonal antibody breast cancer vaccine 11D10 (TriAb) was administered before and after autologous stem cell transplantation (ASCT) in 45 patients with metastatic breast cancer whose disease was responsive to conventional chemotherapy. Evidence of a positive anti-anti-idiotype antibody (Ab3) humoral response was noted at a median of 1.76 months post-ASCT (range, before ASCT-6 months) with this strategy. Maximal Ab3 levels and idiotype-specific T-cell proliferative responses were observed at a median of 3 and 4 months, respectively, after ASCT. The achievement of rapid immune responses after ASCT, during a known period of decreased immunoresponsiveness, opens the possibility of an additional antitumor effect at a time when the tumor burden is relatively small. Moreover, in this interim analysis, patients with the most vigorous humoral and cellular immune responses had a significant improvement in progression-free survival. Further follow-up and evaluation of this approach is warranted.
Asunto(s)
Anticuerpos Antiidiotipos/inmunología , Neoplasias de la Mama/terapia , Vacunas contra el Cáncer/uso terapéutico , Glucolípidos/inmunología , Glicoproteínas/inmunología , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Anticuerpos Monoclonales , Neoplasias de la Mama/inmunología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Celular , Gotas Lipídicas , Activación de Linfocitos , Persona de Mediana Edad , Tasa de Supervivencia , Linfocitos T/inmunología , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Between April 1997 and March 1998 we evaluated the immune response and outcome in 11 chemosensitive patients who were treated with the anti-idiotype antibody vaccine TriAb after recovery from intensive therapy and autologous stem cell transplant (ASCT). Triab was commenced after recovery from the acute effects of ASCT; a minimum interval of 1 month was required from completion of consolidation radiotherapy, if given. Nine patients (82%) manifest anti-anti-idiotype antibody (Ab3) responses post ASCT. The maximal Ab3 response was seen after a median of 10 doses (range 5-20), which corresponded to a median of 14 months (range 5-19) post ASCT. Evidence of a T cell proliferative response was seen in eight patients; the response was modest in most of these. At a median follow-up of 24 months (range 22-33) after ASCT, four patients are alive without evidence of disease progression. All four of these patients were in the subgroup with more vigorous immune responses. Subsequent efforts have been directed toward the achievement of higher levels of immune responses more rapidly post ASCT. Bone Marrow Transplantation (2000) 26, 729-735.
Asunto(s)
Anticuerpos Antiidiotipos/uso terapéutico , Neoplasias de la Mama/terapia , Vacunas contra el Cáncer/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Anticuerpos Antiidiotipos/toxicidad , Antígenos de Neoplasias/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/inmunología , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/toxicidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunoterapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Metástasis Linfática/inmunología , Activación de Linfocitos , Persona de Mediana Edad , Factores de Tiempo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Microsporidia are increasingly recognized as opportunistic infections in immunodeficient patients, predominantly patients with AIDS. The two microsporidia most commonly associated with disease in AIDS patients are Enterocytozoon bieneusi and Encephalitozoon intestinalis (previously known as Septata intestinalis). The most common clinical presentation of microsporidiosis in AIDS patients is diarrhea, most commonly caused by the Enterocytozoon bieneusi species. Encephalitozoon intestinalis is a recently described species that has been reported to cause disseminated human infection including cholangitis. We report a case of AIDS cholangiopathy that presented with abdominal pain and cholestatic liver tests. Ultrasound examination and ERCP revealed a picture of sclerosing cholangitis. Bile samples obtained at ERCP were negative for microsporidia; stool studies for microsporidia and cryptosporidia were also negative. No organisms were identified on routine light microscopy of the biopsy specimens from the duodenum, ampulla, and bile duct. E. intestinalis spores were demonstrated in the bile duct biopsies, by methylene blue and azure 11 staining and confirmed by electron microscopy. Albendazole therapy was successful in eradicating E. intestinalis with clinical improvement and improvement in CD4 count. However, the cholangiographic picture did not improve and repeat cholangiography revealed progressive bile duct injury. Albendazole therapy was delayed and may have been too late to prevent bile duct damage; the drug had to be approved by the US Food and Drug Administration for compassionate use. This is an unusual case of sclerosing cholangitis caused by an unusual organism and requiring biliary sphincterotomy and stent placement for progressive stricturing despite eradication of the infection.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/parasitología , Colangitis Esclerosante/parasitología , Encephalitozoon/aislamiento & purificación , Encefalitozoonosis/parasitología , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Albendazol/uso terapéutico , Animales , Antiprotozoarios/uso terapéutico , Conductos Biliares/parasitología , Conductos Biliares/ultraestructura , Biopsia con Aguja , Colangiopancreatografia Retrógrada Endoscópica , Colangitis Esclerosante/diagnóstico , Colangitis Esclerosante/tratamiento farmacológico , Diagnóstico Diferencial , Encefalitozoonosis/diagnóstico , Encefalitozoonosis/tratamiento farmacológico , Humanos , MasculinoRESUMEN
Microangiopathic hemolytic anemia (MAHA) is a well-described complication of stem cell transplantation. Plasmapheresis is one modality utilized as therapy for patients who develop this complication. However, plasmapheresis may alter whole blood levels of certain medications and its effect on tacrolimus in bone marrow transplant patients is unknown. Because tacrolimus has a narrow therapeutic range, the effect of plasmapheresis on whole blood concentrations would be important to know. We report three allogeneic BMT patients who were receiving tacrolimus as acute GVHD therapy while undergoing plasmapheresis for MAHA. Tacrolimus levels seemed unaffected by plasmapheresis in these patients.
Asunto(s)
Anemia Hemolítica/etiología , Anemia Hemolítica/prevención & control , Trasplante de Médula Ósea/efectos adversos , Inmunosupresores/sangre , Plasmaféresis , Tacrolimus/sangre , Adulto , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Lactante , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Trasplante HomólogoRESUMEN
Fifteen cancer patients, deemed blood HSC "mobilization failures" due to CD34 + cell yields of < 0.5 x 10(6) /kg from two consecutive daily cytaphereses, underwent G-CSF primed autologous bone marrow harvest in an attempt to obtain adequate hematopoietic support for subsequent autotransplantation. CD34 + cell yields from the primed marrow harvest were variable; however, some patients had > 5-fold increases in CD34 + cell yields in the marrow compared to cytapheresis, and 4 patients had CD34 + cell yields of > 1.0 (i.e., 1.2, 1.44, 1.61 and 2.45) x 10(6) /kg from the primed marrow harvest. None of the five patients previously exposed to stem cell toxins or fludarabine achieved > 0.85 x 10(6) /kg CD34 + cells with the primed marrow harvest. A significant difference was noted between G-CSF primed blood and marrow for CD34 + cells but not for GM-CFU ( p = 0.011 and p = 0.135, respectively, paired t-test). All evaluable patients engrafted; a median ANC > 0.5 x 10(9) /L recovery was achieved on D + 12 (range + 9 to + 17) in 12 of 13 evaluable patients - one died on D + 9 without recovery. The last day of platelet transfusion occurred at a median D + 13 (range + 8 to > + 66); only one patient remained platelet transfusion-dependent beyond D + 34. As anticipated, patients with higher numbers of CD34 + cells transplanted had somewhat more rapid recoveries. Although stem cell damage is obviously a key factor in mobilization failure patients, these findings raise the possibility that poor mobilization, at least in some patients, results from a mechanism other than, or in addition to, simple stem cell damage. Moreover, they raise the issue of the minimum number of marrow CD34 + - or more arguably other - cells needed for adequate short- and long-term reconstitution. The role of G-CSF in this situation, especially regarding dose and/or schedule, is intriguing but remains to be clarified. G-CSF primed marrow harvest is a potential option in certain poor mobilizers but, as fully expected, is frequently inadequate. Whether such is preferable to "steady-state" marrow harvest, continued or repeated G-CSF primed cytapheresis (with or without chemotherapy), or primed marrow with G-CSF in other schedules - or with other cytokines - is unclear and will be the subject of further study.