RESUMEN
OBJECTIVE: Necrotising otitis externa is increasingly being seen and treated within the UK. The aim of this study was to explore the potential cost of a cohort of patients with necrotising otitis externa presenting to a single tertiary NHS trust. METHOD: This was a retrospective study with data from 14 patients with confirmed necrotising otitis externa who were treated, monitored, discharged or who died between October 2016 and November 2018. Direct costs using the tariffs from the 2018 to 2019 financial year included in-patient stay, imaging, peripheral inserted central catheter line cost, ENT and out-patient parenteral antibiotic therapy visits and antimicrobial duration. RESULTS: The mean cost of treatment per patient was £17 615 (range, £9407 to £38 230) with an extreme outlier costing more than £122 000. CONCLUSION: Awareness and education at a primary care level and research into robust imaging to aid termination of treatment may lower costs in the future by catching pathology early and reducing treatment duration.
Asunto(s)
Otitis Externa , Antibacterianos/uso terapéutico , Estrés Financiero , Humanos , Otitis Externa/tratamiento farmacológico , Estudios Retrospectivos , Medicina EstatalRESUMEN
BACKGROUND: Malignant otitis externa is a potentially fatal infection of the skull base. With an ageing population and increasing prevalence of diabetes, the incidence of malignant otitis externa in the British population is rising. To date, there remain no accepted diagnostic criteria, few prognostic indicators and no consensus treatment pathways. METHOD: A prospective case series was conducted at a tertiary referral teaching hospital. RESULTS: A cohort of susceptible individuals predominates (elderly, male, with immunosuppression and diabetes), with 25 per cent reporting a preceding incident. Otorrhoea, otalgia and canal granulation were the commonest presenting features, alongside positive pseudomonas cultures. No clear markers for predicating disease severity were isolated; however, a high initial haemoglobin A1c level demonstrated a significant moderately positive correlation with length of treatment. CONCLUSION: A treatment pathway designed to provide a standardised approach to investigation and treatment is proposed, which aims to increase earlier diagnosis, streamline care and facilitate the development of best practice.
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Algoritmos , Sistemas de Apoyo a Decisiones Clínicas , Neoplasias del Oído/terapia , Otitis Externa/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Oído/diagnóstico , Femenino , Hospitales de Enseñanza , Humanos , Masculino , Persona de Mediana Edad , Otitis Externa/diagnóstico , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Reino UnidoRESUMEN
OBJECTIVES: To compare the difference in ENT and Audiology visits, treatments dispensed and potential savings pre- and post-bone anchored hearing aid (BAHA) insertion in patients with chronic suppurative otitis media exacerbated by behind the ear hearing aids. DESIGN: A retrospective pilot study. SETTING: District General Hospital. PARTICIPANTS: All patients who had BAHA inserted from January 2001 to January 2006. PARAMETERS: Age, gender, number of visits per month, treatments per month dispensed from the ENT and Audiology Departments and direct and limited indirect medical costs pre- and post-BAHA insertion. RESULTS: Twelve of 26 (46%) adult patients had BAHA inserted over the 5-year period for CSOM. The male to female ratio was 1 : 3 with a median age of 61 (range 29-81). The number of visits and treatments dispensed per month in the ENT Department fell from a mean of 0.42-0.33 (P < 0.08) and 0.22-0.14 (P < 0.02) respectfully. When the difference in medical cost was taken into account BAHA offered a potential saving of pound 627.80 per patient. CONCLUSION: Although the initial acquisition of surgical equipment and BAHA sound processors is expensive, there is a reduction in the number of treatments and visits required for patients with chronic suppurative otitis media after BAHA is inserted leading to a reduction in average costs.
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Audífonos/economía , Otitis Media Supurativa/rehabilitación , Adulto , Anciano , Anciano de 80 o más Años , Atención Ambulatoria/estadística & datos numéricos , Costos y Análisis de Costo , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Reino UnidoRESUMEN
OBJECTIVE: This paper highlights the importance of reporting air-bone gap closure in stapes surgery according to the American Academy of Otolaryngology - Head and Neck Surgery guidelines and reviews compliance in recent years. METHODS: A retrospective case series was conducted and the outcomes were reviewed. Closure of the air-bone gap was calculated in 204 adult patients using the aforementioned guidelines. Results were recalculated ignoring the Carhart phenomenon to determine any significant difference. Adherence to guidelines was also reported as a secondary outcome. RESULTS: Ignoring the Carhart phenomenon resulted in 75 per cent over-reporting of successful air-bone gap closure (p < 0.001). Over-reporting occurred in 5.9 per cent of papers, and in 11.8 per cent it was difficult to determine how the results were reached. CONCLUSION: Despite the existence of clear guidelines, stapes surgery outcomes are still being over-reported as successful. This can lead to incorrect information being provided to patients during the consent process and makes comparative studies difficult.
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Conducción Ósea/fisiología , Documentación/normas , Adhesión a Directriz , Pérdida Auditiva Conductiva/cirugía , Otosclerosis/cirugía , Cirugía del Estribo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Audiometría , Femenino , Pérdida Auditiva Conductiva/etiología , Humanos , Masculino , Persona de Mediana Edad , Otosclerosis/complicaciones , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Bait collection is a multibillion dollar worldwide activity that is often managed ineffectively. For managers to understand the impacts on protected inter-tidal mudflats and waders at appropriate spatial scales macrofaunal surveys combined with video recordings of birds and bait collectors were undertaken at two UK sites. Dug sediment constituted approximately 8% of the surveyed area at both sites and is less muddy (lower organic content) than undug sediment. This may have significant implications for turbidity. Differences in the macrofaunal community between dug and undug areas if the same shore height is compared as well as changes in the dispersion of the community occurred at one site. Collection also induces a 'temporary loss of habitat' for some birds as bait collector numbers negatively correlate with wader and gull abundance. Bait collection changes the coherence and ecological structure of inter-tidal mudflats as well as directly affecting wading birds. However, as ß diversity increased we suggest that management at appropriate hectare/site scales could maximise biodiversity/function whilst still supporting collection.
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Biodiversidad , Aves , Ecosistema , Animales , EcologíaRESUMEN
The A-chain of the plant toxin abrin was covalently linked to monoclonal anti-Thy 1.1 antibody (OX7) with the use of either N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) or 2-iminothiolane hydrochloride (2IT). The SPDP reagent generates a linkage containing a disulfide bond and an amide bond, whereas the 2IT reagent generates a linkage containing a disulfide bond and an amidinium bond. The two immunotoxins were powerfully and specifically toxic to Thy 1.1-expressing murine AKR-A lymphoma cells in vitro. Both reduced the rate of protein synthesis of the cells by 50% at a concentration of 10(-11) M. However, clonogenic assays revealed that about 1% of the AKR-A cells survived treatment with high concentrations of OX7-SPDP-abrin A, whereas only about 0.1% survived treatment with similar concentrations of OX7-2IT-abrin A. Several clones of the surviving cells were isolated. Of 11 clones of cells that had survived exposure to OX7-SPDP-abrin A, 10 were resistant to further treatment with OX7-SPDP-abrin A but had normal sensitivity to OX7-2IT-abrin A. These clones expressed moderate to high levels of the Thy 1.1 antigen and were fully sensitive to abrin. In contrast, all 10 clones of cells that had survived exposure to OX7-2IT-abrin A were substantially or entirely resistant to both immunotoxins. They expressed low to high levels of the Thy 1.1 antigen and were fully sensitive to abrin. The 2IT-linked immunotoxin was much more effective than the SPDP-linked immunotoxin at protecting nu/nu mice against the growth of AKR-A lymphoma cells in the peritoneal site. A single iv injection of 0.3 nmol OX7-2IT-abrin A eradicated at least 99.99% of the tumor cells, as judged from the extension in the median survival time of the animals, whereas OX7-SPDP-abrin A eradicated only about 99% of the cells. The tumors that developed in the animals that received OX7-2IT-abrin A were Thy 1.1-negative, whereas those in the recipients of OX7-SPDP-abrin A generally expressed normal levels of the Thy 1.1 antigen. The difference in antitumor activity of the immunotoxins was not due to differences in their in vivo fate, inasmuch as they were cleared from the bloodstream at an identical rate and broke down at the same rate to release free antibody.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Abrina/farmacología , Reactivos de Enlaces Cruzados/farmacología , Inmunotoxinas/farmacología , Neoplasias Experimentales/terapia , Proteínas de Plantas/farmacología , Abrina/uso terapéutico , Animales , Antígenos de Superficie/análisis , Supervivencia Celular/efectos de los fármacos , Inmunotoxinas/metabolismo , Inmunotoxinas/uso terapéutico , Isoanticuerpos/uso terapéutico , Linfoma/terapia , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos BALB C , Antígenos Thy-1 , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
The carbohydrate present on ricin A chain causes ricin A chain immunotoxins to be cleared rapidly in animals by the reticuloendothelial system. In an effort to overcome this problem we destroyed the carbohydrate on ricin A chain by treating it with a mixture of sodium metaperiodate and sodium cyanoborohydride and then linked the "deglycosylated" A chain to monoclonal anti-Thy 1.1 antibody. The deglycosylation procedure did not affect the ability of the A chain component of the immunotoxin to inhibit protein synthesis in a cell-free system or the capacity of the immunotoxin to inhibit protein synthesis in Thy-1.1 positive lymphoma cells in vitro. Immunotoxins prepared with deglycosylated A chain were cleared from the bloodstream of mice more slowly than native ricin A chain immunotoxins. The difference in the blood clearance rates of the two immunotoxins could be accounted for by a decreased entrapment of the deglycosylated ricin A chain immunotoxin by the liver. Both immunotoxins broke down in vivo with the appearance of free antibody in the bloodstream. The site of cleavage of the immunotoxin was possibly the liver because immunotoxins taken up by it rapidly became unreactive with antiricin but retained reactivity with anti-mouse immunoglobulin G suggesting that dissociation of the A chain from the antibody had occurred. The immunotoxins taken up by the liver were metabolized further and the acid insoluble radioactive metabolites gradually accumulated in the stomach, thyroid, and salivary gland. The deglycosylated ricin A chain immunotoxin should be a more effective antitumor agent in vivo because it is cleared from the blood more slowly and so has greater opportunity to localize within the tumor target.
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Inmunotoxinas/farmacología , Isoanticuerpos/uso terapéutico , Ricina/uso terapéutico , Animales , Técnicas de Cultivo , Citotoxicidad Inmunológica , Glicosilación , Semivida , Isoanticuerpos/administración & dosificación , Cinética , Hígado/metabolismo , Linfoma/tratamiento farmacológico , Ratones , Ricina/administración & dosificación , Distribución TisularRESUMEN
Two new coupling agents were synthesized for making immunotoxins containing disulfide bonds with improved stability in vivo: sodium S-4-succinimidyloxycarbonyl-alpha-methyl benzyl thiosulfate (SMBT) and 4-succinimidyloxycarbonyl-alpha-methyl-alpha(2-pyridyldithio)tolue ne (SMPT). Both reagents generate the same hindered disulfide linkage in which a methyl group and a benzene ring are attached to the carbon atom adjacent to the disulfide bond and protect it from attack by thiolate anions. An immunotoxin consisting of monoclonal anti-Thy-1.1 antibody (OX7) linked by means of the SMPT reagent to chemically deglycosylated ricin A-chain had better stability in vivo than an immunotoxin prepared with 2-iminothiolane hydrochloride (2IT) which generates an unhindered disulfide linkage. About 48 h after i.v. injection into mice, one-half of the SMPT-linked immunotoxin present in the blood was in intact form and one-half as released free antibody, whereas equivalent breakdown of the 2IT-linked immunotoxin was seen at about 8 h after injection. Consequently, the blood levels of the SMPT-linked immunotoxin remained higher than those of the 2IT-linked immunotoxin despite loss of immunotoxin from the blood by other mechanisms. Forty-eight h after injection, 10% of the injected dose of the SMPT-linked immunotoxin remained in the bloodstream as compared with only 1.5% of the 2IT-linked immunotoxin. The ability of immunotoxins prepared with the new reagents to inhibit protein synthesis by Thy-1.1-expressing AKR-A/2 lymphoma cells in vitro was identical to that of immunotoxins prepared with 2IT or N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). Clonogenic assays showed that fewer than 0.01% of AKR-A/2 cells survived exposure to high concentrations of OX7-abrin A-chain immunotoxins prepared with SMBT, 2IT, or SPDP. Twelve clones of cells which had survived treatment with the SMBT-linked immunotoxin were isolated. None of the clones was selectively resistant to the SMBT-linked immunotoxin when retested in cytotoxicity assays. In conclusion, immunotoxins prepared with the new coupling agents should have improved antitumor activity in vivo because they are longer lived and do not break down so readily to release free antibody which could compete for the target antigens.
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Inmunotoxinas , Animales , Anticuerpos Monoclonales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Fenómenos Químicos , Química , Disulfuros , Estabilidad de Medicamentos , Inmunoglobulina G , Inmunotoxinas/metabolismo , Inmunotoxinas/farmacología , Indicadores y Reactivos , Masculino , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos , Relación Estructura-ActividadRESUMEN
Immunotoxins containing the ribosome-inactivating protein, saporin, are very effective antitumor agents but are highly toxic to mice. They induce severe necrotic lesions in the liver parenchyma of the recipients. Such extensive damage to the liver parenchyma is not observed with ricin A-chain immunotoxins even at 5-fold higher dosage. The hepatotoxicity of the saporin immunotoxins was found in the present study to arise from a combination of two effects. First, saporin and saporin immunotoxins were 30- and 6-fold more toxic to primary cultures of mouse liver parenchymal cells than were ricin A-chain and ricin A-chain immunotoxins, respectively. This was despite the fact that the cells bound 4- to 5-fold less saporin or saporin immunotoxins than ricin A-chain or ricin A-chain immunotoxins. The binding of ricin A-chain and its immunotoxin to the cells was mediated through the carbohydrate residues present on the A-chain whereas saporin is not glycosylated and thus must bind to other sites on the cell surface which result in transport of saporin relatively efficiently to the cytosol. The second reason for the hepatotoxic action of the saporin immunotoxin was that it had a longer blood half-life (t 1/2 alpha = 1.1 h; t 1/2 beta = 17.1 h) than the ricin A-chain immunotoxin (t 1/2 = 0.52 h; t 1/2 beta = 9.7 h). Analyses using a two-compartment pharmacokinetic model showed that the two immunotoxins broke down in vivo to give free antibody at a similar rate (t 1/2 = 10-12 h) but that the ricin A-chain immunotoxin was eliminated 11 times more rapidly than the saporin immunotoxin by routes other than breakdown. It was calculated that, in mice given a median lethal dose of saporin immunotoxin, the blood levels of immunotoxin remained above the concentration that killed 50% of parenchymal cells in vitro for more than 48 h. In mice given a median lethal dose of ricin A-chain immunotoxin, the blood levels fell below the concentration that was toxic to parenchymal cells in vitro within 4 h. The longer blood half-life of the saporin immunotoxin may also explain our previous finding that it had antitumor activity superior to that of a ricin A-chain immunotoxin in mice.
Asunto(s)
Inmunotoxinas/farmacocinética , Hígado/efectos de los fármacos , N-Glicosil Hidrolasas , Proteínas de Plantas/toxicidad , Ricina/farmacocinética , Animales , Células Cultivadas , Semivida , Matemática , Ratones , Proteínas de Plantas/farmacocinética , Proteínas Inactivadoras de Ribosomas Tipo 1 , Ricina/toxicidad , SaporinasRESUMEN
A monoclonal anti-Thy-1.1 antibody (OX7) was coupled to either native or chemically deglycosylated ricin A-chain (dgA) using one of two different cross-linking agents. One cross-linker, N-succinimidyloxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio)tolu ene (SMPT), generates a sterically hindered disulfide bond which is relatively resistant to reduction, whereas the other, 2-iminothiolane hydrochloride, generates an unhindered disulfide bond with greater lability. A two-compartment pharmacokinetic model was used to analyze the blood levels of each immunotoxin and its breakdown product (free antibody) after i.v. injection into mice. Immunotoxins prepared with SMPT broke down in vivo 6.3-fold more slowly than those prepared with 2-iminothiolane hydrochloride, and immunotoxins containing native A-chain were cleared 2- to 3-fold more rapidly from the bloodstream than those containing dgA. As a result, 24 h after injection, 16% of the OX7-SMPT-dgA remained in the blood as compared with 0.4 to 2.5% of the other immunotoxins. Immunotoxins prepared with dgA were about 3-fold more toxic to mice than those prepared with native A-chain, whereas immunotoxins prepared with SMPT were only slightly more toxic than those prepared with 2-iminothiolane hydrochloride. When equivalent toxic doses of the immunotoxins were administered i.v. to mice which had been given injections of Thy-1.1+ AKR-A/2 lymphoma cells, the OX7-SMPT-dgA gave the best antitumor effect. A dose equivalent to one-seventh of the median lethal dose extended the survival time of the animals by the extent expected if 99.999% of the tumor cells had been eradicated. Furthermore, the tumors that did develop in the mice treated with OX7-SMPT-dgA were mutants which were resistant to all the immunotoxins. Some of the mutants were deficient in Thy-1.1 whereas others were not. In conclusion, both the use of the SMPT cross-linker and deglycosylation of the A-chain significantly improve the therapeutic index of the immunotoxins in AKR-A/2 tumor-bearing mice.
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Antineoplásicos/farmacología , Inmunotoxinas/farmacología , Ricina/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Estabilidad de Medicamentos , Femenino , Glicosilación , Inmunotoxinas/metabolismo , Isoanticuerpos/inmunología , Dosificación Letal Mediana , Linfoma/patología , Linfoma/terapia , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos BALB C , Células Tumorales CultivadasRESUMEN
Inhibitors of angiogenesis hold potential in the treatment of cancer and other diseases where the disease is caused or maintained by the inappropriate growth of blood vessels. In the present study, a novel inhibitor of angiogenesis was synthesized by covalently linking a nonanticoagulating derivative of heparin, heparin adipic hydrazide (HAH), by an acid-labile bond to the antiangiogenic steroid, cortisol. The rationale was that the heparin derivative, which binds to sulfated polyanion receptors on endothelial cells, should concentrate the steroid on the surface of vascular endothelial cells. Endocytosis of the conjugate and decomposition of the acid-labile linkage inside lysosomes and other acidic intracellular compartments should then lead to release of the cortisol and expression of its antiproliferative activity. Analysis of the stability of HAH-cortisol showed that it was stable at pH 7.4 and broke down rapidly (t1/2 15 min) at pH 4.8 at 37 degrees C. Treatment of murine pulmonary capillary endothelial cells with HAH-cortisol at 10(-5) M (with respect to cortisol) suppressed their DNA synthesis by 50% and inhibited their migration into wounded areas of confluent monolayers. HAH-cortisol at 10(-4) M (with respect to cortisol) did not suppress the DNA synthesis of Lewis lung carcinoma cells. Daily i.p. injections of HAH-cortisol into mice bearing s.c. sponge implants retarded vascularization of the sponge, and injections directly into the sponge abolished vascularization for as long as the injections were continued. Daily i.v. injections of HAH-cortisol at doses causing no apparent toxicity retarded the growth of solid s.c. Lewis lung carcinomas in mice by up to 65%. In all of these assays, equivalent treatments with a mixture of the HAH plus cortisol was significantly less effective. The antiproliferative effect of HAH-cortisol on endothelial cells appeared independent of the glucocorticoid activity of the steroid since HAH conjugated to 5 beta-pregnane-3 alpha,17 alpha,21-triol-20-one, a steroid lacking glucocorticoid or mineralocorticoid activity, was even more effective at inhibiting DNA synthesis by murine pulmonary capillary endothelial cells than was HAH-cortisol. In conclusion, HAH-cortisol represents the prototype of a new class of angiogenesis inhibitors for the treatment of cancer and other angiogenic diseases.
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Heparina/análogos & derivados , Heparina/uso terapéutico , Hidrocortisona/análogos & derivados , Hidrocortisona/uso terapéutico , Neoplasias Pulmonares/irrigación sanguínea , Neovascularización Patológica/prevención & control , Animales , Anticoagulantes/uso terapéutico , Anticoagulantes/toxicidad , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , División Celular/efectos de los fármacos , Células Cultivadas , Cortodoxona/análogos & derivados , Cortodoxona/uso terapéutico , ADN de Neoplasias/biosíntesis , Estabilidad de Medicamentos , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Heparina/toxicidad , Hidrocortisona/toxicidad , Concentración de Iones de Hidrógeno , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , PorcinosRESUMEN
Ricin B chain incubated at 37 degrees C in the absence of lactose loses its ability to bind the galactose-containing protein, asialofetuin. Circular dichroism analysis of the B chain during thermal denaturation indicates that the loss of galactose-binding ability by the B chain correlates with limited unfolding of the molecule. As a result of this conformational change, disulfide bonds that are shielded from the solvent by the compact folded structure of the B chain become exposed and the chitobiosyl cores of both N-linked oligomannose chains become susceptible to cleavage by endoglycosidases. The heat-denatured B chain does not enhance the toxicity of a ricin A chain-containing rabbit anti-human immunoglobulin (RAHIg-A) to Daudi cells. However, when heat-denatured B chain is coupled to goat anti-rabbit immunoglobulin (GARIg), the resulting immunotoxin, GARIg-hdB, potentiates the killing of RAHIg-A-treated Daudi cells to an extent similar to that of an immunotoxin prepared with GARIg and native B chain. These results indicate that the native, galactose-binding structure of the B chain is not necessary to enhance the cytotoxicity of the cell-reactive A chain immunotoxin (IT-A) and suggests that regions of the B chain exposed by unfolding the molecule may mediate potentiation of cytotoxicity.
Asunto(s)
Adyuvantes Inmunológicos/toxicidad , Citotoxinas/toxicidad , Galactosa/metabolismo , Ricina/toxicidad , Línea Celular , Disulfuros , Sinergismo Farmacológico , Calor , Humanos , Conformación Proteica , Desnaturalización Proteica , Receptores de Superficie Celular/fisiología , Relación Estructura-ActividadRESUMEN
OBJECTIVE: The aim of this paper was to propose a guideline for the management of intrinsic facial nerve tumours based on our practice and findings in the literature. METHOD: A retrospective review of intrinsic facial nerve tumours over the last 15 years was performed. Parameters measured included age, presenting symptoms, pre- and post-treatment hearing and House-Brackmann grading, tumour position, treatment and duration of follow up. RESULTS: A total of 15 patients presented with intrinsic facial nerve tumours over the study period. The most common presenting complaint was facial symptoms (93.3 per cent), followed by hearing loss (46.7 per cent). Three patients with stable facial nerve function (House-Brackmann grades II-III) were treated conservatively. Twelve patients underwent surgery to treat progressive or recurrent symptoms. Facial function was maintained or improved in 60.0 per cent of patients and hearing was preserved in 66.7 per cent. CONCLUSION: We propose that all stable tumours associated with good facial function of grade III or below should be treated conservatively. For symptomatic or progressive lesions, tailored surgery depending on the tumour site and hearing level should be offered to preserve native nerve function and facial musculature. For patients with prolonged paralysis, tumours can be monitored and other forms of facial reanimation and support offered.
Asunto(s)
Neoplasias de los Nervios Craneales/cirugía , Enfermedades del Nervio Facial/cirugía , Parálisis Facial/terapia , Hueso Temporal/inervación , Adulto , Anciano , Neoplasias de los Nervios Craneales/complicaciones , Nervio Facial/cirugía , Enfermedades del Nervio Facial/complicaciones , Parálisis Facial/etiología , Femenino , Pérdida Auditiva/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Since the development of intratympanic aminoglycoside in the 1950s, otologists have been able to chemically ablate the vestibule. We present the results of using low-dose intratympanic gentamicin to treat Ménière's disease. METHOD: A retrospective review was performed of all patients who underwent low-dose intratympanic gentamicin therapy over seven years. Data on gender, age, number of procedures, pure tone audiometry and symptom control were analysed. RESULTS: In all, 38 patients underwent low-dose intratympanic gentamicin therapy. These comprised 25 females and 13 males, with an average age of 58.4 years. Hearing was preserved in 87.5 per cent of patients, with no significant difference before and after treatment (p = 0.744). In all, 85.7 per cent of patients had complete or substantial symptom control (classes A and B, respectively). CONCLUSION: Low-dose intratympanic gentamicin therapy was effective in controlling the symptoms of Ménière's disease patients, while preserving hearing.
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Antibacterianos/administración & dosificación , Gentamicinas/administración & dosificación , Enfermedad de Meniere/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Audiometría de Tonos Puros , Estudios de Cohortes , Femenino , Humanos , Inyección Intratimpánica , Masculino , Enfermedad de Meniere/fisiopatología , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The present study investigates the relationships between copper (Cu) and zinc (Zn) concentrations in sediment, pore water and their bioaccumulation in the polychaete Nereis (Alitta) virens, as well as the importance of site-specific sediment characteristics in that process. Sediment, pore water and N. virens were sampled from seven sites with different pollution histories along the English Channel coast. Results showed that site-specific metal levels and sediment characteristics were important in determining the bioavailability of metals to worms. Significant correlations were found between Cu in the sediment and in the pore water and between Zn in the pore water and in N. virens. Zn from the pore water was thus more readily available from a dissolved source to N. virens than Cu. Data also showed that metal concentrations in N. virens were lower than those found in other closely related polychaetes, indicating that it may regulate tissue concentrations of Cu and Zn.
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Monitoreo del Ambiente/métodos , Metales/análisis , Poliquetos/fisiología , Contaminantes Químicos del Agua/análisis , Animales , Disponibilidad Biológica , Cobre , Sedimentos Geológicos/química , Metales/metabolismo , Agua , Contaminantes Químicos del Agua/metabolismo , ZincRESUMEN
OBJECTIVE: This study investigated whether patients who remain symptomatic more than a year following idiopathic facial paralysis gain benefit from tailored facial physiotherapy. METHODS: A two-year retrospective review was conducted of all symptomatic patients. Data collected included: age, gender, duration of symptoms, Sunnybrook facial grading system scores pre-treatment and at last visit, and duration of treatment. RESULTS: The study comprised 22 patients (with a mean age of 50.5 years (range, 22-75 years)) who had been symptomatic for more than a year following idiopathic facial paralysis. The mean duration of symptoms was 45 months (range, 12-240 months). The mean duration of follow up was 10.4 months (range, 2-36 months). Prior to treatment, the mean Sunnybrook facial grading system score was 59 (standard deviation = 3.5); this had increased to 83 (standard deviation = 2.7) at the last visit, with an average improvement in score of 23 (standard deviation = 2.9). This increase was significant (p < 0.001). CONCLUSION: Tailored facial therapy can improve facial grading scores in patients who remain symptomatic for prolonged periods.
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Parálisis de Bell/terapia , Modalidades de Fisioterapia/estadística & datos numéricos , Adulto , Anciano , Toxinas Botulínicas Tipo A/uso terapéutico , Músculos Faciales , Nervio Facial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares/uso terapéutico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
DNA encoding ricin A chain was derived from preproricin cDNA and ligated into the expression vector pDS5/3. Transcription is controlled from the coliphage promoter PN25 fused with the lac operator of E.coli. When induced, E.coli 71.18 cells transformed with the recombinant plasmid express ricin A chain which is soluble and has full biological activity.
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Escherichia coli/metabolismo , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes/biosíntesis , Ricina/biosíntesis , ADN/genética , Vectores Genéticos , Humanos , Regiones Operadoras Genéticas , Regiones Promotoras Genéticas , Biosíntesis de Proteínas/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Ricina/genética , Ricina/farmacologíaRESUMEN
An electrothermal atomic absorption method for the determination of antimony in biological fluids, derived from Triostam or Pentostam, is described. Comparison of the results obtained by this method has been made with hydride generation atomic absorption and by measuring the gamma emission of 125Sb-Pentostam. Using electrothermal atomic absorption, the concentrations and distributions of the pentavalent and trivalent antimony drugs, either in free or liposome-entrapped forms, have been determined in vitro after incubation with human blood. The effect of entrapping Pentostam within liposomes has also been studied in vivo in mice, and its concentration and distribution compared with results obtained using the free drug.
Asunto(s)
Antimonio/análisis , Animales , Antimonio/sangre , Humanos , Liposomas , Hígado/análisis , Ratones , Espectrofotometría Atómica/métodos , Bazo/análisisRESUMEN
Endocrine and environmental factors control reproduction of the polynoid scale worm Harmothoe imbricata. We confirmed that the rate of vitellogenesis was greater in winter specimens transferred from ambient regimes of photoperiod and temperature to a light:dark (LD) photoperiod of 16:8 at 10 degrees C and showed that the number of females spawning was significantly greater than for those transferred to LD8:16 at 10 degrees C. The endocrine mediation of this response was investigated using prostomium implantations. Significantly more LD8:16 females implanted with prostomia from LD16:8 conditioned females spawned than LD8:16 females implanted with LD8:16 prostomia. Females without prostomia failed to spawn. LD16:8 exposure may increase levels of a possible "spawning hormone" in the prostomium. Spawning proceeded in these LD16:8 females and allowed spawning to occur in LD8:16 females implanted with LD16:8 prostomia. In LD8:16 prostomia, titers of the spawning hormone reached the threshold in significantly fewer individuals, so that significantly fewer females implanted with LD8:16 prostomia spawned. Using Y-maze choice chambers, pair formation was shown to be under pheromonal control, with males being attracted to mature females but not to females carrying fertilized oocytes or to LD8:16 conditioned females. Production of this attraction pheromone can, therefore, be manipulated through photoperiodic control, suggesting a link between oogenesis, spawning, and pheromone production.
Asunto(s)
Poliquetos/fisiología , Animales , Sistema Endocrino/fisiología , Femenino , Masculino , Oocitos/crecimiento & desarrollo , Apareamiento , Feromonas/fisiología , Fotoperiodo , Poliquetos/metabolismoRESUMEN
Sex and scents have long been associated. Musk, for example, is a sexual scent that has been used for many years in the perfume industry. In humans, the debate on the existence of sex pheromones continues, whereas in insects their role is well known. Through recent research, we are discovering that such chemicals are equally important in conveying sexual signals between aquatic animals.