RESUMEN
The title compound, C6H2F4N2O, displays amide bond lengths of 1.218â (3)â Å and 1.366â (3)â Å for the C=O and C-N bonds, respectively. The Cp-N-C-O (p = pyridine) torsion angle of 179.0â (2)° indicates an anti-conformation for the grouping. Inter-molecular hydrogen bonding is observed between the amine N-H group and the carbonyl O atom, which generates chains of mol-ecules propagating along the b-axis direction.
RESUMEN
Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential role in protecting cell viability through modulation of oxidative stress. TRPM2 is highly expressed in cancer. When TRPM2 is inhibited, mitochondria are dysfunctional, ROS levels are increased, and cell viability is reduced. Here, the importance of NF-E2-related factor (Nrf2) in TRPM2-mediated suppression of oxidant stress was explored. In TRPM2 depleted cells, antioxidant cofactors glutathione, NADPH, and NADH were significantly reduced. Cytoplasmic and nuclear expression of Nrf2 and of IQGAP1, a modulator of Nrf2 stability regulated by intracellular calcium, were decreased. Antioxidant enzymes transcriptionally regulated by Nrf2 and involved in GSH, NADPH, and NADH generation were significantly lower including PRX1 and PRX3, GPX4, GSTP1, GCLC, and MTHFD2. The glutamine pathway leading to GSH production was suppressed, and ATP and GTP levels were impaired. Reconstitution with wild type TRPM2 or Nrf2, but not TRPM2 pore mutant E960D, rescued expression of enzymes downstream of Nrf2 and restored GSH and GTP. Cell viability, ROS, NADPH, NADH, and ATP levels were fully rescued by TRPM2 and partially by Nrf2. These data show that TRPM2 maintains cell survival following oxidative stress through modulation of antioxidant pathways and cofactors regulated by Nrf2.
Asunto(s)
Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Canales Catiónicos TRPM/metabolismo , Animales , Antioxidantes/metabolismo , Calcio/metabolismo , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/fisiología , Femenino , Glutatión/metabolismo , Humanos , Ratones , Mitocondrias/metabolismo , Oxidantes/metabolismo , Estrés Oxidativo/fisiología , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Adult-type rhabdomyoma (ATR) is a rare mesenchymal tumor of skeletal muscle differentiation. Extracardiac ATR occurs most commonly in the head and neck, but do so in a heterogeneous fashion, arising at numerous different locations within this region. METHODS: At our institution, we encountered a patient who was diagnosed clinically with parathyroid adenoma based on signs and symptoms of hyperparathyroidism and suggestive radiologic findings. A parathyroidectomy with intraoperative consultation was performed. RESULTS: The frozen section diagnosis was ambiguous and a diagnosis of ATR was only made on permanent section. CONCLUSION: Awareness of this tumor can prevent incorrect diagnosis and overtreatment intraoperatively. Herein, we describe the clinical history, pathologic findings, and review histologic features of rhabdomyomas.
Asunto(s)
Adenoma/diagnóstico , Neoplasias de las Paratiroides/diagnóstico , Rabdomioma/diagnóstico , Anciano de 80 o más Años , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias de las Paratiroides/cirugía , Paratiroidectomía , Rabdomioma/cirugíaRESUMEN
BACKGROUND: Interest in vitamin D has increased during the past 2 decades, with a corresponding increase in laboratory testing of 25-hydroxyvitamin D [25(OH)D]. The vast majority of specimens tested display normal or deficient levels of 25(OH)D; concentrations rarely fall in the potentially toxic range. METHODS: We performed a retrospective investigation of elevated 25(OH)D levels during a 16-year period at the University of Iowa Hospitals and Clinics (UIHC), a 734-bed tertiary-/quaternary-care academic medical center in the midwestern United States. Detailed medical-record review was performed for patients with serum/plasma 25(OH)D concentrations higher than 120 ng per mL. RESULTS: A total of 127,932 serum/plasma 25(OH)D measurements were performed on 73,779 unique patients. Of these patients, 780 (1.05%) had results that exceeded 80 ng per mL and 89 patients (0.12%) had results that exceeded 120 ng per mL. Only 4 patients showed symptoms of vitamin D toxicity. Three of these cases involved inadvertent misdosing of liquid formulations. CONCLUSIONS: Symptomatic vitamin D toxicity is uncommon, and elevated levels of 25(OH)D do not strongly correlate with clinical symptoms or total serum/plasma calcium levels. Our study highlights the potential risks of the liquid formulation of vitamin D.
Asunto(s)
Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Calcio/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Iowa , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vitamina D/sangre , Vitamina D/uso terapéutico , Vitamina D/toxicidad , Adulto JovenRESUMEN
AIMS: Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. METHODS AND RESULTS: We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours. Immunohistochemistry for PHOX2B was performed with a rabbit monoclonal antibody. PHOX2B positivity was defined as the presence of nuclear immunoreactivity in ≥5% of cells. PHOX2B was positive in 70 (92%) peripheral neuroblastic tumours, including 68 of 72 (94%) paediatric and two of four (50%) adult cases. Furthermore, PHOX2B was consistently negative in all non-peripheral neuroblastic tumours, with staining being absent in 160 cases and limited in four cases. CONCLUSION: PHOX2B is a highly sensitive and specific immunohistochemical marker for peripheral neuroblastic tumours, including neuroblastoma. PHOX2B reliably distinguishes neuroblastoma from histological mimics such as Wilms tumour, Ewing sarcoma, and CIC-rearranged round cell sarcoma. PHOX2B negativity in two of four adult neuroblastoma cases raises the possibility that some adult neuroblastomas are of a different lineage than paediatric cases.
Asunto(s)
Biomarcadores de Tumor/análisis , Proteínas de Homeodominio/biosíntesis , Neuroblastoma/diagnóstico , Factores de Transcripción/biosíntesis , Adolescente , Adulto , Anciano , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Proteínas de Homeodominio/análisis , Humanos , Lactante , Recién Nacido , Neoplasias Renales/diagnóstico , Masculino , Persona de Mediana Edad , Sarcoma de Células Pequeñas/diagnóstico , Sensibilidad y Especificidad , Factores de Transcripción/análisis , Tumor de Wilms/diagnóstico , Adulto JovenRESUMEN
AIMS: Paired-like homeobox 2b (PHOX2B) is a transcription factor with expression outside of the central nervous system restricted to neurons and chromaffin cells of the autonomic nervous system. Germline mutations cause congenital central hypoventilation syndrome and predispose to neuroblastoma and Hirschsprung disease. Among paediatric small round cell tumours, PHOX2B is neuroblastoma-specific. Two studies of adult autonomic nervous system tumours (n = 62) produced conflicting results (all tumours stained in one; expression restricted to 40% of paragangliomas in the other). We examined PHOX2B expression in a large cohort of phaeochromocytomas and paragangliomas, as well as well-differentiated neuroendocrine tumours (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs). METHODS AND RESULTS: Tissue microarrays (TMAs) were constructed from 609 tumours: 111 phaeochromocytomas, 146 paragangliomas, 250 WDNETs, and 102 PDNECs. PHOX2B immunohistochemistry was scored for extent (%) and intensity (0-3+), and an H-score (extent × intensity) was calculated. PHOX2B expression was seen in 32% of phaeochromocytomas and in 47% of paragangliomas. Mean/median H-scores for these tumours were in the 30-55 range (i.e. weak to moderate staining). No WDNETs and only 7% of PDNECs stained, the latter often strongly. In a representative cohort of corresponding whole sections (n = 55), the results in WDNETs and PDNECs were unchanged, whereas half of the phaeochromocytomas/paragangliomas that were negative on TMAs became focally, weakly positive. CONCLUSIONS: We found frequent, weak to moderate PHOX2B expression in phaeochromocytomas/paragangliomas and no expression in WDNETs, which could be diagnostically useful in the distinction of these tumours. Expression in a minority of PDNECs probably reflects the transcription factor lineage infidelity that is characteristic of this tumour class.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/metabolismo , Proteínas de Homeodominio/metabolismo , Neuroblastoma/patología , Tumores Neuroendocrinos/metabolismo , Paraganglioma/metabolismo , Feocromocitoma/metabolismo , Factores de Transcripción/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Estudios de Cohortes , Proteínas de Homeodominio/genética , Humanos , Neuroblastoma/metabolismo , Tumores Neuroendocrinos/patología , Paraganglioma/patología , Feocromocitoma/patología , Análisis de Matrices Tisulares , Factores de Transcripción/genéticaRESUMEN
Small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) and mantle cell lymphoma (MCL) usually are distinctly different in regard to clinical presentation, morphology, immunophenotype and molecular/genetic findings. In spite of this, select cases may show overlapping characteristics and represent a diagnostic challenge. Recently LEF1 staining was identified as a fairly characteristic finding in CLL/SLL, with positivity identified in up to 95% of cases. LEF1 staining has not been reported as being present in cases of MCL, making this stain a useful tool in distinguishing these diagnoses. We identified an index case of MCL with cyclin D1 expression and the presence of the typical t(11;14) IGH-CCND1, which expressed LEF1. Subsequently, we assessed LEF1 immunohistochemical staining in a series of 23 cases of MCL, as confirmed by staining for cyclin D1 and/or SOX11. We found expression present in one additional case, and evaluated some published literature suggesting a frequency of 4-9% expression of LEF1 by MCL. LEF1 expression by immunohistochemistry in MCL is unusual but can be seen rarely, and could represent a potential diagnostic pitfall.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Leucemia Linfocítica Crónica de Células B/metabolismo , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/patología , Diagnóstico Diferencial , Humanos , Inmunohistoquímica/métodos , Inmunofenotipificación/métodos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células del Manto/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in modulating cell survival following oxidant injury and is highly expressed in many cancers including neuroblastoma. Here, in xenografts generated from neuroblastoma cells in which TRPM2 was depleted with CRISPR/Cas9 technology and in in vitro experiments, tumor growth was significantly inhibited and doxorubicin sensitivity increased. The hypoxia-inducible transcription factor 1/2α (HIF-1/2α) signaling cascade including proteins involved in oxidant stress, glycolysis, and mitochondrial function was suppressed by TRPM2 depletion. TRPM2-depleted SH-SY5Y neuroblastoma cells demonstrated reduced oxygen consumption and ATP production after doxorubicin, confirming impaired cellular bioenergetics. In cells in which TRPM2 was depleted, mitochondrial superoxide production was significantly increased, particularly following doxorubicin. Ectopic expression of superoxide dismutase 2 (SOD2) reduced ROS and preserved viability of TRPM2-depleted cells, however, failed to restore ATP levels. Mitochondrial reactive oxygen species (ROS) were also significantly increased in cells in which TRPM2 function was inhibited by TRPM2-S, and pretreatment of these cells with the antioxidant MitoTEMPO significantly reduced ROS levels in response to doxorubicin and protected cell viability. Expression of the TRPM2 pore mutant E960D, in which calcium entry through TRPM2 is abolished, also resulted in significantly increased mitochondrial ROS following doxorubicin treatment, showing the critical role of TRPM2-mediated calcium entry. These findings demonstrate the important function of TRPM2 in modulation of cell survival through mitochondrial ROS, and the potential of targeted inhibition of TRPM2 as a therapeutic approach to reduce cellular bioenergetics, tumor growth, and enhance susceptibility to chemotherapeutic agents.
Asunto(s)
Señalización del Calcio , Glucólisis , Mitocondrias/metabolismo , Proteínas de Neoplasias/metabolismo , Neuroblastoma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Canales Catiónicos TRPM/metabolismo , Sustitución de Aminoácidos , Calcio , Línea Celular Tumoral , Supervivencia Celular , Eliminación de Gen , Humanos , Mitocondrias/genética , Mitocondrias/patología , Mutación Missense , Proteínas de Neoplasias/genética , Neuroblastoma/genética , Neuroblastoma/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Canales Catiónicos TRPM/genéticaRESUMEN
INTRODUCTION: We describe the uses and efficacy of botulinum toxin injection to the inferior rectus muscle in vertical strabismus resulting from orbital pathology. METHODS: A retrospective review of patients undergoing inferior rectus botulinum toxin injection between 1982 and 2006 for vertical strabismus due to orbital pathology. RESULTS: There were 13 patients identified; 6 with idiopathic orbital inflammatory syndrome (IOIS) including myositis, 3 with previous orbital wall fractures, 1 post-optic nerve sheath Schwannoma resection, 1 with lymphoma, 1 with metastasis, and 1 post-superior ophthalmic vein hemorrhage. A beneficial effect with inferior rectus botulinum toxin was obtained in 9/13 (69%) patients (mean follow-up 14 months). Resolution or improvement occurred in 4/6 (67%) patients with IOIS. Resolution was also obtained in the patient with previous optic nerve sheath Schwannoma resection, and the patient who sustained the superior ophthalmic vein hemorrhage. Improvement was noted in both the patient with lymphoma and in the patient with a metastasis. However, in patients with orbital wall fractures, only 1 of 3 patients obtained improvement. Benefit appeared independent of the size of vertical deviation, with 4/6 (67%) showing improvement with a pre-toxin angle 4-12 PD, and 5/7 (71%) improving with a pre-toxin angle 16-25 PD. Eleven patients received only 1 injection, one patient received 2, and another had an ongoing course of 8 injections. DISCUSSION: Vertical strabismus secondary to a range of orbital conditions, particularly inflammatory, often can be successfully managed by inferior rectus botulinum toxin injections.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Movimientos Oculares/fisiología , Enfermedades Orbitales/complicaciones , Estrabismo/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares/administración & dosificación , Músculos Oculomotores , Estudios Retrospectivos , Estrabismo/etiología , Estrabismo/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
METHODS: Persistent symptomatic strabismus may be seen in up to 25% of patients post retinal detachment surgery. Surgical correction of ocular misalignment in this situation can be technically difficult to perform and the results are less predictable than in other forms of strabismus surgery. We report on our experience of the use of botulinum toxin injections as an alternative. RESULTS: A retrospective review was made of all patients who had received botulinum toxin injections in the management of their strabismus following retinal detachment surgery at our institution between November 1982 and January 2006. One hundred and forty patients fulfilled our criteria with a mean length of follow-up of 27 months. Thirty-three patients (23.6%) were symptom free following botulinum toxin injection alone and were discharged from the clinic, 50.5% of these after only 2 injections. Fusion was regained in 37.9%. The only factor associated with lack of restoration of fusion in the multivariate analysis was visual acuity in the injected eye. Complications were seen in 2.9% of patients. CONCLUSION: Botulinum toxin injections may represent a safe and acceptable alternative to surgery and may be particularly useful for those in whom surgery is contraindicated or not desired.
Asunto(s)
Toxinas Botulínicas/administración & dosificación , Procedimientos Quirúrgicos Oftalmológicos/efectos adversos , Complicaciones Posoperatorias , Desprendimiento de Retina/cirugía , Estrabismo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antidiscinéticos/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Músculos Oculomotores , Estudios Retrospectivos , Estrabismo/etiología , Estrabismo/fisiopatología , Resultado del Tratamiento , Agudeza Visual , Adulto JovenRESUMEN
METHODS: Retrospective case note review of management of patients with bilaterally severely reduced vision presenting with symptomatic strabismus. RESULTS: There were 10 females and 7 males, mean age at treatment was 36 years, range 19 to 74 years. Thirteen patients had an exotropia ranging from 20 to 90(Δ) (mean 52(Δ)). Four had an esotropia ranging from 30 to 70(Δ) (mean 53(Δ)). Vision in each eye ranged from 6/24 Snellen to light perception, except for one patient with Usher's syndrome who had grossly restricted visual fields and vision of 6/12 and 6/36. The etiology was retinitis pigmentosa in 5 patients; 3 had cone dystrophy, 2 were high myopes. Other etiologies included CMV retinitis in both eyes secondary to HIV, bilateral optic atrophy post craniopharyngioma, and cortical visual impairment. All patients were unable to see well enough to assess their strabismus but were aware of its presence from family members and friends and wished improvement. Eleven patients underwent botulinum toxin injections; 2 of these then proceeded to surgery. A total of 8 patients had surgery. Post-operative angles ranged from 6(Δ) to 25(Δ) of esotropia. Five patients continue with maintenance toxin. Follow-up ranged from 3 months to 15 years. DISCUSSION/CONCLUSIONS: This is the first report of patients with bilaterally severely reduced vision requesting treatment for strabismus that they were unable to see for themselves. All patients were pleased they had undergone treatment for their strabismus despite being unable to see the outcome.
Asunto(s)
Músculos Oculomotores/cirugía , Estrabismo/cirugía , Visión Binocular , Baja Visión/complicaciones , Adulto , Anciano , Movimientos Oculares , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Músculos Oculomotores/fisiopatología , Estudios Retrospectivos , Estrabismo/complicaciones , Estrabismo/fisiopatología , Resultado del Tratamiento , Baja Visión/fisiopatología , Agudeza Visual , Adulto JovenRESUMEN
The homoleptic thio-ether title complex, [Ni(C(6)H(12)S(3))(2)](BF(4))(2)·2CH(3)NO(2), shows the expeced hexa-kis-(thio-ether) octa-hedral environment around the Ni(II) atom. It crystallized as two crystallographically independent complex cations, [Ni(9S3)(2)](2+) (9S3 = 1,4,7-trithia-cyclo-nona-ne), within the unit cell where each Ni(II) lies on an inversion center. In addition to the complex cations, there are two crystallographically independent BF(4) (-) anions present to balance the charge, and each shows disorder along a pseudo-C(3) axis with ratios of 0.53â (2):0.47â (2) and 0.55â (2):0.45â (2). Two nitro-methane solvent mol-ecules per complex cation are also present in the unit cell.
RESUMEN
INTRODUCTION: We describe the uses and effectiveness of botulinum toxin to the inferior rectus muscle in iatrogenic vertical strabismus. METHODS: A retrospective review of our database to identify patients who had undergone inferior rectus botulinum toxin injection between 1982 and 2006 for iatrogenic vertical strabismus. RESULTS: There were 13 patients, 5 female, with an age range of 14 to 78 years. Eight left eyes were injected. The mean period of follow-up was 3.3 years. Etiologies included post-local anesthetic, post-plaque radiotherapy for malignant melanoma, adherence syndrome after inferior oblique surgery, and post-botulinum toxin to the levator muscle to produce a temporary therapeutic ptosis. Reversal on first injection occurred in 7 patients and occurred in a further 2 patients on second injection. Pre-injection binocularity was not demonstrable in 3 patients; 2 of these patients did have binocular vision demonstrable after botulinum toxin injection. Seven patients had one injection, 3 patients had two, 1 had three, 1 had five, and 1 had six. DISCUSSION: The data demonstrate the range of indications that can be successfully treated and managed with inferior rectus botulinum toxin injection in iatrogenic vertical strabismus.
Asunto(s)
Antidiscinéticos/administración & dosificación , Toxinas Botulínicas/administración & dosificación , Enfermedad Iatrogénica , Músculos Oculomotores/efectos de los fármacos , Estrabismo/tratamiento farmacológico , Estrabismo/etiología , Adolescente , Adulto , Anciano , Anestésicos Locales/efectos adversos , Antidiscinéticos/efectos adversos , Toxinas Botulínicas/efectos adversos , Braquiterapia/efectos adversos , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The proportion of individuals above retirement age is expanding and consequently there is increased demand for ophthalmic surgery, including strabismus. In 2001 we published a pilot study reviewing all strabismus operations performed on patients aged 60 and over between 1992 and 1999. Almost a decade later, we repeated the analysis, aiming to identify any longitudinal trends. METHODS: Using the hospital information system, we conducted a retrospective review of all elective strabismus surgery in patients aged 60 years and over, performed by one surgeon (JPL) between January 2000 and September 2008. All operations were under general anesthesia. RESULTS: We identified 237 strabismus operations (9.1% of total operations) that were performed in patients aged 60 or over. This is significantly higher compared with the proportion of elderly patients in the previous study (111 patients, 7% of total operations, P=0.015). Gender distribution was similar to our previous study (105 females, 51% vs 59 females, 53.1%, P=0.814). Ages ranged from 60 to 96 years (mean 69.5 ± 6.8). A decade ago, the more common diagnoses were fourth (22%) and sixth (10%) cranial nerve palsies, consecutive (14%) and secondary (9%) strabismus, whereas recently thyroid eye disease (18%), sixth nerve palsy (13%) and iatrogenic (11%) causes have overtaken the other categories (P=0.011). Adjustable sutures were undertaken in 144 patients (61%). CONCLUSION: Strabismus in elderly patients continues to be related to neurogenic etiologies but thyroid eye disease and iatrogenic causes are on the increase. This is the first 10-year longitudinal analysis to be presented, with the caveat that our data are obtained from a single practice.
Asunto(s)
Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos/tendencias , Estrabismo/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Estrabismo/diagnósticoRESUMEN
Exposure to cyanide can occur in a variety of ways, including exposure to smoke from cigarettes or fires, accidental exposure during industrial processes, and exposure from the use of cyanide as a poison or chemical warfare agent. Confirmation of cyanide exposure is difficult because, in vivo, cyanide quickly breaks down by a number of pathways, including the formation of both free and protein-bound thiocyanate. A simple method was developed to confirm cyanide exposure by extraction of protein-bound thiocyanate moieties from cyanide-exposed plasma proteins. Thiocyanate was successfully extracted and subsequently derivatized with pentafluorobenzyl bromide for GC-MS analysis. Thiocyanate levels as low as 2.5 ng mL(-1) and cyanide exposure levels as low as 175 µg kg(-1) were detected. Samples analyzed from smokers and non-smokers using this method showed significantly different levels of protein-bound thiocyanate (p<0.01). These results demonstrate the potential of this method to positively confirm chronic cyanide exposure through the analysis of protein-bound cyanide in human plasma.
Asunto(s)
Proteínas Sanguíneas/química , Cianuros/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Tiocianatos/análisis , Animales , Fluorobencenos/química , Humanos , Fumar , PorcinosRESUMEN
INTRODUCTION: Duane syndrome is a difficult condition to treat. Patients and parents need to be informed that it will not resolve and it is not possible to create normal eye movements surgically. Botulinum toxin may be used to assess the likelihood of reducing the abnormal head posture and reducing the diplopia by increasing the field of binocular single vision. If results are favorable then surgery may be offered. This article is a retrospective review of patients with Duane syndrome treated with botulinum toxin using the toxin clinic database between 1980 and 2007. METHODS: Eighty-eight patients were identified, 48 females and 40 males. The average age at presentation was 29 years, range 5 to 68 years. The left eye was affected in 50 (57%) patients and 21 (24%) patients were affected bilaterally. The average angle was 28.6 +/- 18.4 Delta for the esotropic patients and 32.5 +/- 14.5 Delta for the exotropic patients. In 58 patients the medial rectus was injected, in 30 the lateral rectus. RESULTS: As a result of the outcome of botulinum toxin, 41 (46.5%) patients proceeded to surgery; 12 (14%) continued with maintenance toxin. Forty-seven (53%) demonstrated a long-term reduction in deviation. Transient complications were ptosis in 11 patients and induced vertical deviation in 10. CONCLUSION: This is the first study to explore the diagnostic role of botulinum toxin in Duane syndrome. It is a safe treatment that may also offer long-term benefits.
Asunto(s)
Antidiscinéticos , Toxinas Botulínicas , Síndrome de Retracción de Duane/diagnóstico , Adolescente , Adulto , Anciano , Anestesia General , Anestesia Local , Antidiscinéticos/administración & dosificación , Antidiscinéticos/efectos adversos , Blefaroptosis/inducido químicamente , Toxinas Botulínicas/administración & dosificación , Toxinas Botulínicas/efectos adversos , Niño , Preescolar , Síndrome de Retracción de Duane/fisiopatología , Síndrome de Retracción de Duane/cirugía , Electromiografía , Femenino , Humanos , Inyecciones Intramusculares/métodos , Masculino , Persona de Mediana Edad , Músculos Oculomotores , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To analyze the effectiveness of botulinum toxin injection for convergence spasm. METHODS: Review of the Toxin Clinic database to identify patients who had undergone botulinum toxin injection to the medial rectus muscle for convergence spasm. RESULTS: There were 11 females and 6 males. Average age at treatment was 34 years (range 12-57 years). All patients had a variable esotropia, ranging from 10 to 90+ prism diopters but most could demonstrate some binocular function. All patients had convergence spasm, pupil miosis, and diplopia. Previous treatment included surgery, atropine, plus lenses, and occlusion. Fourteen patients (82%) were temporarily overcorrected after their first injection. Three patients (18%) were symptom free after just one injection and were subsequently discharged, all having been temporarily overcorrected. Seven patients (41%) continue with botulinum toxin on a regular basis, with or without occlusive contact lens, to remain symptom free, two being discharged after the third and fifth injections symptom free. Seven patients found no benefit from this treatment and so were discharged from the clinic or did not attend for follow-up appointments. CONCLUSION: Our rather extensive experience with these patients has led us to conclude that in some patients convergence spasm may be a type of dystonia, and may like other dystonias be suitable for botulinum toxin treatment.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Convergencia Ocular , Fármacos Neuromusculares/administración & dosificación , Músculos Oculomotores , Espasmo/tratamiento farmacológico , Espasmo/fisiopatología , Adolescente , Adulto , Niño , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Carbon-carbon bond formation is the central method by which synthetic chemists add complexity, which often represents value, to molecules. Uniting a carbon chain with an aromatic substrate to yield an alkyl arene product is thus a molecular means of creating value-added materials. A traditional method for generating alkyl arenes is Friedel-Crafts catalysis, in which an alkyl halide or olefin is activated to react with an aromatic substrate. Unfortunately, despite the development of new generations of solid-state catalysts, the reaction often requires relatively harsh conditions and frequently gives poor to moderate selectivity. Conversely, a halide can first be incorporated into the aromatic ring, and the aryl halide can subsequently be joined by a variety of catalytic coupling techniques. But generating the aryl halide itself can be problematic, and such methods typically are not atom-economical. The addition of aromatic C-H bonds across the C-C double bonds of olefins (olefin hydroarylation) is therefore an attractive alternative in the preparation of alkyl arenes. Despite the dominance and practical advantages of heterogeneous catalysts in industrial synthesis, homogeneous systems can offer an enhanced ability to fine-tune catalyst activity. As such, well-defined homogeneous catalysts for the hydroarylation of olefins provide a potentially promising avenue to address issues of selectivity, including the production of monoalkylated arene products and the control of linear-to-branched ratios for synthesis of long-chain alkyl arenes, and provide access to more ambient reaction conditions. However, examples of homogeneous catalysts that are active for the conversion of unactivated aromatic and olefin substrates to alkyl arene products that function via metal-mediated C-H activation pathways are limited. In this Account, we present results from research aimed at the development of Ru(II) catalysts supported by the hydridotris(pyrazolyl)borate (Tp) ligand for the addition of aromatic C-H bonds across olefins. On the basis of detailed mechanistic studies with TpRu(L)(NCMe)R catalysts, in which the neutral ancillary ligand L is varied, we have arrived at guidelines for the development of improved catalysts that are based on the octahedral-d6 motif.
RESUMEN
BACKGROUND: In the healthcare system in the United Kingdom, a number of patients may be offered botulinum toxin as an alternative to surgery in the treatment of their strabismus. We report on our experience of treating those who have received 25 or more injections. METHODS: A retrospective review of the botulinum toxin clinic database was used to identify patients who underwent 25 or more injections between November 1982 and January 2006. All patients with strabismus who met this criterion were included. A statistical analysis was performed in which we compared aspects of this group with those who had received 24 or fewer injections. RESULTS: Fifty-seven patients (0.90%) fulfilled our criteria. There were 37 women and 20 men, with a mean age at first injection of 39 years (range, 15 to 80 years). The number of injections per patient ranged from 25 to 68 (mean, 34). The duration of treatment was between 3 and 22 years. The time interval between injections tended to increase in most patients and the angle tended to reduce. There was no statistical difference between the age at first injection, sex, site injected, diagnosis, and complication rate between the long-term group and the group that received 24 or fewer injections. The long-term group, however, had undergone more previous operations (p < or = 0.001) and had a lower degree of binocularity (p = 0.001). CONCLUSIONS: The treatment of strabismus with botulinum toxin on a long-term basis is practicable and valuable in patients with poor binocular potential, complicated strabismus, or multiple previous strabismus operations. A trend toward fewer injections with time was observed, and no significant adverse effects were observed with long-term treatment.
Asunto(s)
Toxinas Botulínicas/administración & dosificación , Estrabismo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Toxinas Botulínicas/efectos adversos , Toxinas Botulínicas/economía , Bases de Datos Factuales , Esquema de Medicación , Esotropía/tratamiento farmacológico , Exotropía/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Costos de la Atención en Salud , Humanos , Inyecciones Intramusculares/estadística & datos numéricos , Masculino , Registros Médicos , Persona de Mediana Edad , Músculos Oculomotores , Estudios Retrospectivos , Estrabismo/fisiopatología , Estrabismo/cirugía , Resultado del Tratamiento , Visión Binocular , Agudeza Visual , Adulto JovenRESUMEN
The authors report the results of a retrospective review of patients who underwent nasal transposition of the vertical rectus muscles between 1997 and 2004. Eight patients were identified, 4 males and 4 females. There was an average age at surgery of 37 years, with a range from 8 to 79 years. The aetiologies included 6 patients with trauma to their medial rectus (4 following endoscopic sinus surgery) and 2 patients with paralytic medial rectus muscles secondary to 3rd nerve palsy. All patients underwent whole tendon transposition of the superior and inferior rectus muscles, with resection of both muscles in 7 cases, before reattachment adjacent to the upper and lower borders of the medial rectus, respectively. One patient had a reduced amount of resection and this was combined with inferior oblique disinsertion and traction sutures. All patients had a reduction in deviation in the primary position and in 5 patients there was some improvement in adduction. A consequence of surgery was a degree of limitation of abduction, elevation and depression in some patients. Overall, patients were satisfied with the improvement in their appearance.