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1.
Clin Endocrinol (Oxf) ; 89(2): 178-186, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29781512

RESUMO

OBJECTIVE: Rathke's cleft cyst (RCC) is a common sellar lesion which may cause visual impairment, hypopituitarism and headaches from mass effect. The natural history of these lesions is currently unclear. We investigated the natural history of RCCs and compared surgically treated patients with those treated conservatively. METHODS: We performed a retrospective cohort study of patients diagnosed with a RCC between 1996 and 2016 at Stanford University and Ospedale Maggiore Policlinico di Milano. RESULTS: Patients were divided into 2 cohorts: Group A, 72 subjects who underwent surgical resection of a symptomatic RCC, and Group B, 62 subjects managed conservatively. Compared to Group B, Group A subjects had larger RCCs (79% vs 22% had a largest diameter >10 mm, P < .001) and were more likely (41.5% vs 16%, P < .001) to present with hypopituitarism and diabetes insipidus (DI) (18% vs 1.6%, P = .002). In Group A, after a mean follow-up of 53.7 months, 12.5% of patients had recurrence and a second surgery. After surgery, 35% of patients recovered pituitary function. Hyperprolactinemia (26.6%) and hypogonadism (66.6%) resolved more commonly that did DI (20.1%). New pituitary deficits appeared in 16.6% of patients after surgery. In Group B, with a mean follow-up of 41 months, only 6.4% had cyst enlargement, none underwent surgery, and none developed a pituitary deficit. CONCLUSION: Our data offer guidance in decision-making regarding the management of RCC patients and confirm the safety of conservative treatment in asymptomatic patients.

2.
J Neurooncol ; 136(1): 207-212, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29098569

RESUMO

Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11 months. Similarly, the risk of local tumor recurrence following SRS is < 5% after 18 months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as > 18 months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement > 18 months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2 months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9 months (range 18.5-63.2 months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2 months and 7 lesions had late LF occurring a median of 23.6 months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3 years and local failure up to 3.8 years following SRS in our cohort.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Radiocirurgia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/secundário , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Lesões por Radiação/etiologia , Estudos Retrospectivos
3.
J Neurooncol ; 138(2): 291-298, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29429125

RESUMO

Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5-50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6-84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.


Assuntos
Acromegalia/terapia , Adenoma/terapia , Neoplasias Hipofisárias/terapia , Radiocirurgia , Procedimentos Cirúrgicos Robóticos , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento
4.
J Neurooncol ; 139(1): 135-143, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29623552

RESUMO

INTRODUCTION: Maximizing extent of surgical resection with the least morbidity remains critical for survival in glioblastoma patients, and we hypothesize that it can be improved by enhancements in intraoperative tumor detection. In a clinical study, we determined if therapeutic antibodies could be repurposed for intraoperative imaging during resection. METHODS: Fluorescently labeled cetuximab-IRDye800 was systemically administered to three patients 2 days prior to surgery. Near-infrared fluorescence imaging of tumor and histologically negative peri-tumoral tissue was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratios (TBRs) were calculated by comparing MFIs of tumor and histologically uninvolved tissue. RESULTS: The mean TBR was significantly higher in tumor tissue of contrast-enhancing (CE) tumors on preoperative imaging (4.0 ± 0.5) compared to non-CE tumors (1.2 ± 0.3; p = 0.02). The TBR was higher at a 100 mg dose than at 50 mg (4.3 vs. 3.6). The smallest detectable tumor volume in a closed-field setting was 70 mg with 50 mg of dye and 10 mg with 100 mg. On sections of paraffin embedded tissues, fluorescence positively correlated with histological evidence of tumor. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (73.0% for 50 mg dose, 98.2% for 100 mg dose) and specific (66.3% for 50 mg dose, 69.8% for 100 mg dose) for viable tumor tissue in CE tumors while normal peri-tumoral tissue showed minimal fluorescence. CONCLUSION: This first-in-human study demonstrates the feasibility and safety of antibody based imaging for CE glioblastomas.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Imagem Óptica , Cirurgia Assistida por Computador , Antineoplásicos Imunológicos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/patologia , Cetuximab , Relação Dose-Resposta a Droga , Corantes Fluorescentes , Glioblastoma/patologia , Humanos , Indóis , Imagem Óptica/métodos , Sensibilidade e Especificidade , Espectroscopia de Luz Próxima ao Infravermelho , Cirurgia Assistida por Computador/métodos
5.
J Vet Pharmacol Ther ; 41(3): 374-377, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29383736

RESUMO

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida-infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0-2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1-2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high-performance liquid chromatography. The values of elimination half-life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*µg/ml, 3.63 hr* hr*µg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*µg/ml, 9.85 hr* hr*µg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida-infected rabbits.


Assuntos
Cefalosporinas/farmacocinética , Infecções por Pasteurella/veterinária , Pasteurella multocida , Coelhos , Animais , Área Sob a Curva , Cefalosporinas/uso terapêutico , Feminino , Meia-Vida , Infecções por Pasteurella/tratamento farmacológico , Infecções por Pasteurella/microbiologia
6.
Stem Cells ; 34(6): 1702-7, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26991945

RESUMO

Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs coexisting in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to divergent bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. Stem Cells 2016;34:1702-1707.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Células-Tronco Neoplásicas/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Glioblastoma/genética , Humanos , Fenótipo , Análise de Célula Única , Transcrição Gênica
7.
Mo Med ; 113(4): 288-292, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-30228480

RESUMO

The U.S. health care system relies on primary care physicians to provide the majority of the dermatologic care-dermatologists see an estimated 30-40% of patients with dermatologic issues.1 Issues related to skin and mucous membrane conditions account for an estimated 8% of all visits to Family Physicians.2 Thus the primary care physician must be prepared to assess patients' with conditions benign or malignant, cosmetic or grave, irritants or harbingers of systemic illness, pathological or normal variant. In this article, three commonly seen and difficult to treat conditions will be reviewed.

8.
J Eur Acad Dermatol Venereol ; 29(9): 1679-88, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25664493

RESUMO

The risks, financial costs and lengthy downtime associated with surgical procedures for fat reduction have led to the development of a number of non-invasive techniques. Non-invasive body contouring now represents the fastest growing area of aesthetic medicine. There are currently four leading non-invasive techniques for reducing localized subcutaneous adipose tissue: low-level laser therapy (LLLT), cryolipolysis, radio frequency (RF) and high-intensity focused ultrasound (HIFU). To review and compare leading techniques and clinical outcomes of non-invasive subcutaneous fat reduction. The terms 'non-invasive', 'low-level laser', 'cryolipolysis', 'ultrasound' and 'radio frequency' were combined with 'lipolysis', 'fat reduction' or 'body contour' during separate searches in the PubMed database. We identified 31 studies (27 prospective clinical studies and four retrospective chart reviews) with a total of 2937 patients that had been treated with LLLT (n = 1114), cryolipolysis (n = 706), HIFU (n = 843) or RF (n = 116) or other techniques (n = 158) for fat reduction or body contouring. A majority of these patients experienced significant and satisfying results without any serious adverse effects. The studies investigating these devices have all varied in treatment regimen, body locations, follow-up times or outcome operationalization. Each technique differs in offered advantages and severity of adverse effects. However, multiple non-invasive devices are safe and effective for circumferential reduction in local fat tissue by 2 cm or more across the abdomen, hips and thighs. Results are consistent and reproducible for each device and none are associated with any serious or permanent adverse effects.


Assuntos
Crioterapia/métodos , Lipectomia/métodos , Terapia com Luz de Baixa Intensidade/métodos , Gordura Subcutânea , Terapia por Ultrassom/métodos , Humanos , Satisfação do Paciente
9.
J Eur Acad Dermatol Venereol ; 29(7): 1275-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25589056

RESUMO

Onychomycosis is a common fungal infection of the nails that is increasing in prevalence in the old, diabetics and immunocompromised. Onychomycosis presents a therapeutic challenge that can lead to significant reductions in quality of life leading to both physical and psychological consequences. Current treatment modalities are difficult to implement due to the poor penetration of topical treatments to the nail bed, the slow growing nature of nails and the need for prolonged use of topical and/or oral medications. Standard of care medications have cure rates of 63-76% that leads to a high propensity of treatment failures and recurrences. Photodynamic therapy (PDT) offers an alternative treatment for onychomycosis. Methylene blue dye, methyl-aminolevulinate (MAL) and aminolevulinic acid (ALA) have been used as photosensitizers with approximately 630 nm light. These modalities are combined with pre-treatment of urea and/or microabrasion for better penetration. PDT treatments are well tolerated with only mild transient pain, burning and erythema. In addition, significant cure rates for patients who have contraindications to oral medications or failed standard medications can be obtained. With further enhancements in photosensitizer permeability, decreased pre-treatment and photosensitizer incubation times, PDT can be a more efficient and cost-effective in office based treatment for onychomycosis. However, more large-scale randomized control clinical trials are needed to access the efficacy of PDT treatments.


Assuntos
Onicomicose/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Humanos , Qualidade de Vida , Resultado do Tratamento
10.
J Eur Acad Dermatol Venereol ; 29(6): 1045-52, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25418614

RESUMO

Benign familial chronic pemphigus, or Hailey-Hailey disease (HHD), is a recurrent bullous dermatitis that tends to have a chronic course with frequent relapses. Long-term treatment options include surgery with skin grafting or dermabrasion. Both are highly invasive and carry significant risks and complications. More recently, 'laser-abrasion' has been described as a less invasive option with a better side-effect profile. In this article, we systematically review the safety and efficacy of carbon dioxide laser therapy as a long-term treatment option for HHD, as well as provide a review of other lasers that have been reported with this goal. A total of 23 patients who had been treated with a carbon dioxide laser were identified. After treatment, 10 patients (43%) had had no recurrence, 10 (43%) had greater than 50% improvement, 2 (8%) had less than 50% improvement and 1 (4%) patient had no improvement at all (follow-up period ranged from 4 to 144 months). Laser parameter variability was wide and adverse effects were minimal, including dyspigmentation and scarring. Reviewed evidence indicates this therapy offers a safe, effective treatment alternative for HHD with minimal risk of side-effects. Larger, well-designed studies are necessary to determine the optimal treatment parameters.


Assuntos
Lasers de Gás/uso terapêutico , Pênfigo Familiar Benigno/cirurgia , Dióxido de Carbono , Cicatriz/etiologia , Humanos , Lasers de Corante/uso terapêutico , Lasers de Gás/efeitos adversos , Lasers Semicondutores/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Transtornos da Pigmentação/etiologia , Recidiva , Resultado do Tratamento
11.
J Eur Acad Dermatol Venereol ; 29(11): 2080-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25731611

RESUMO

Sebaceous gland hyperplasia (SGH) is a benign cutaneous condition that presents primarily on the face and increases with UVB exposure and ageing. These lesions are a common cosmetic concern but are difficult to treat, as the entire sebaceous gland needs to be destroyed to prevent recurrence. Traditional methods of treatment include: cryosurgery, electrodessication, curettage, shave excision and topical trichloroacetic acid. These methods have an increased risk of skin discoloration and scarring to the area of treatment that may lead to inferior cosmetic outcomes. Alternatively, oral isotretinoin can treat SGH, but is a known teratogen in pregnancy and has high relapse rates with discontinuation. A systematic review of the literature was performed to look at photodynamic therapy (PDT) and laser treatment for SGH. According to the results of this study, PDT, lasers and combinations of the two treatments were found to offer alternatives to the more conventional techniques with better outcomes. In particular, the use of wavelength-specific laser for the sebaceous gland of 1720 nm were found to have better outcomes and provide minimal damage to surrounding tissues. Additionally, combination PDT with aminolevulinic acid and pre-treatment with carbon dioxide laser ablation or pulse-dyed laser offered higher cure rates over stand-alone laser or PDT treatments in a shorter number of sessions with similar transient side-effects. However, further large-scale prospective studies with adequate follow-up are required to confirm these findings and those for sebaceous gland-specific lasers.


Assuntos
Terapia a Laser , Fotoquimioterapia , Glândulas Sebáceas/patologia , Terapia Combinada , Humanos , Hiperplasia/terapia , Terapia a Laser/métodos , Fotoquimioterapia/métodos
12.
J Eur Acad Dermatol Venereol ; 29(11): 2100-3, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25845405

RESUMO

Argyria is a benign skin disease characterized by blue to slate-grey discoloration that is caused by deposition of silver granules in the skin and/or mucus membranes as a result of long-term ingestion of ionized silver solutions or exposure to airborne silver particles. The skin discoloration can be generalized or localized and is exacerbated by sunlight. The skin discoloration is usually permanent, and until recently, there has been no effective treatment for argyria. Over the past 6 years, a number of case reports and one case series have described cases of argyria that were successfully treated with a 1064 nm Q-switched (QS) neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; however, a review of these studies has never been reported in the dermatologic literature. To review the use of the 1064 nm QS Nd:YAG laser for the treatment of argyria. A search of the National Library of Medicine's PubMed Database and the SCOPUS Database was performed to find articles that detailed the treatment of argyria with 1064 nm QS Nd:YAG laser. Six articles were selected for inclusion in this review. Each article was reviewed and summarized in a table. A 1064 nm QS Nd:YAG laser offers a novel and effective treatment for argyria. A systematic review of the dermatologic literature revealed a limited number of case reports and case series using this treatment. However, the results gleaned by the authors from the literature review provide important information to the clinician. For patients with argyria, a single pass of the 1064 nm QS Nd:YAG laser offers immediate, effective and sustained pigment clearing without any long-term adverse effects.


Assuntos
Argiria/radioterapia , Lasers de Estado Sólido/uso terapêutico , Humanos , Lasers de Estado Sólido/efeitos adversos , Recidiva
13.
Proc Natl Acad Sci U S A ; 109(17): 6662-7, 2012 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-22451913

RESUMO

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.


Assuntos
Antígenos de Diferenciação/metabolismo , Antígeno CD47/imunologia , Neoplasias/imunologia , RNA Mensageiro/genética , Receptores Imunológicos/metabolismo , Anticorpos/imunologia , Antígeno CD47/genética , Divisão Celular/imunologia , Citometria de Fluxo , Humanos , Neoplasias/patologia , Neoplasias/terapia , Fagocitose/imunologia , Prognóstico , Análise de Sobrevida
14.
N Engl J Med ; 364(7): 627-37, 2011 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-21175304

RESUMO

BACKGROUND: Amplification and activating mutations of the epidermal growth factor receptor (EGFR) oncogene are molecular hallmarks of glioblastomas. We hypothesized that deletion of NFKBIA (encoding nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor-α), an inhibitor of the EGFR-signaling pathway, promotes tumorigenesis in glioblastomas that do not have alterations of EGFR. METHODS: We analyzed 790 human glioblastomas for deletions, mutations, or expression of NFKBIA and EGFR. We studied the tumor-suppressor activity of NFKBIA in tumor-cell culture. We compared the molecular results with the outcome of glioblastoma in 570 affected persons. RESULTS: NFKBIA is often deleted but not mutated in glioblastomas; most deletions occur in nonclassical subtypes of the disease. Deletion of NFKBIA and amplification of EGFR show a pattern of mutual exclusivity. Restoration of the expression of NFKBIA attenuated the malignant phenotype and increased the vulnerability to chemotherapy of cells cultured from tumors with NFKBIA deletion; it also reduced the viability of cells with EGFR amplification but not of cells with normal gene dosages of both NFKBIA and EGFR. Deletion and low expression of NFKBIA were associated with unfavorable outcomes. Patients who had tumors with NFKBIA deletion had outcomes that were similar to those in patients with tumors harboring EGFR amplification. These outcomes were poor as compared with the outcomes in patients with tumors that had normal gene dosages of NFKBIA and EGFR. A two-gene model that was based on expression of NFKBIA and O(6)-methylguanine DNA methyltransferase was strongly associated with the clinical course of the disease. CONCLUSIONS: Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival.


Assuntos
Deleção de Genes , Genes erbB-1 , Glioblastoma/genética , Proteínas I-kappa B/genética , Análise Mutacional de DNA , Amplificação de Genes , Expressão Gênica , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Inibidor de NF-kappaB alfa , Prognóstico , Células Tumorais Cultivadas
15.
J Eur Acad Dermatol Venereol ; 28(12): 1610-22, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25073648

RESUMO

Vitiligo is a disorder of pigmentation affecting about 1% of the global population. It is a psychologically devastating disease with suboptimal treatment options. Narrowband ultraviolet B (NB-UVB) phototherapy has become a first-line choice for treating generalized disease. In recent years, topical calcineurin inhibitors, vitamin D analogues, antioxidant agents and other therapies have been combined with NB-UVB to improve its efficacy. This article will address what is known about the mechanisms of action of these treatments and how they may complement NB-UVB on a cellular level, as well as offer a comprehensive, evidence-based review of clinical outcomes with combination therapies.


Assuntos
Fototerapia , Raios Ultravioleta , Vitiligo/terapia , Humanos
16.
Avian Dis ; 58(1): 8-15, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24758107

RESUMO

Ring-necked pheasants raised on propagation farms can be severely parasitized with Syngamus trachea (gapeworm) and other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic that is not currently approved for game bird species in the United States. The objective of this work was to provide target animal safety data to support a label claim for fenbendazole in pheasants at 100 parts per million (ppm) in the feed for 7 consecutive days. Demonstration of safety in young pheasants and a separate demonstration of reproductive safety in adult birds were required. In the young bird study, 160 Chinese ring-necked pheasants (Phasianus colchicus, 80 males and 80 females) were fed a commercial game bird starter ration containing no antibiotics, growth promoters, or coccidiostats until day 0 of the study (approximately 21 days of age). On day 0 the birds were placed on their respective study diets containing fenbendazole at 0, 100, 300, and 500 ppm for 21 days (three times the normal treatment duration). Clinical observations were recorded twice daily. Feed consumption, feed conversion rate, and body weights were determined for each pen. Three birds from each pen were randomly selected for necropsy, histopathology, and clinical pathology. Birds were carefully examined for feathering abnormalities immediately following euthanasia. The remaining birds in each pen were submitted for drug concentration analysis so that concentrations (for low vs. high treatment levels) could be correlated with clinical observations, clinical pathology, and histologic findings. There no morbidities or mortalities after study day--1. There were no statistically significant treatment-related differences in feed consumption, feed conversion rates, body weights, serum biochemistry profiles, hematologic profiles, gross necropsy findings, histopathologic examination, and feathering. Allowable liver and muscle concentrations of fenbendazole sulfone in turkeys are 6 and 2 ppm, respectively, with a 6-hr feed withdrawal. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young pheasants and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, two large game bird farms fed fendbendazole at 100 ppm for 7 days and collected data on hatching percentage of pheasant eggs before and after treatment. Reproductive performance in hen pheasants was not adversely affected.


Assuntos
Antinematódeos/efeitos adversos , Antinematódeos/metabolismo , Fenbendazol/efeitos adversos , Fenbendazol/metabolismo , Galliformes/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/veterinária , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Feminino , Masculino , Reprodução/efeitos dos fármacos , Distribuição Tecidual
17.
Neurosciences (Riyadh) ; 19(1): 43-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24419449

RESUMO

Colloid cysts, benign outgrowths from the roof of the third ventricle, warrant resection when they become symptomatic. Historically, this has been performed by craniotomy and a transcortical or a transcallosal approach that employs a pair of fixed blade retractors and an operating microscope. Less invasive endoscopic techniques have employed rigid endoscopes with single or dual working channels. We report the use of a tubular retractor as a transcortical port to resect a third ventricular colloid cyst. A 29-year-old woman presented with headache. The brain imaging demonstrated a third ventricular colloid cyst. We describe transcortical, transforaminal resection of a colloid cyst using stereotactically guided placement of a tubular retractor, endoscopic visualization, and bimanual dissection with traditional microinstruments. The increased range of viewing angles of the endoscope within the cylinder of access maintained by the tubular retractor facilitates resection of the cyst through a smaller opening.


Assuntos
Cistos Coloides/cirurgia , Microcirurgia/métodos , Neuroendoscopia/métodos , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Microcirurgia/instrumentação , Tomografia Computadorizada por Raios X
18.
Phys Rev Lett ; 111(10): 102001, 2013 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-25166656

RESUMO

Various theories beyond the standard model predict new particles with masses in the sub-eV range with very weak couplings to ordinary matter. A new P-odd and T-odd interaction between polarized and unpolarized nucleons proportional to K·r is one such possibility, where r is the distance between the nucleons and K is the spin of the polarized nucleon. Such an interaction involving a scalar coupling gs at one vertex and a pseudoscalar coupling gp at the polarized nucleon vertex can be induced by the exchange of spin-0 bosons. We used the NMR cell test station at Northrop Grumman Corporation to search for NMR frequency shifts in polarized 129Xe and 131Xe when a nonmagnetic zirconia rod is moved near the NMR cell. Long (T2∼20 s) spin-relaxation times allow precision measurements of the NMR frequency ratios, which are insensitive to magnetic field fluctuations. Combined with existing theoretical calculations of the neutron spin contribution to the nuclear angular momentum in xenon nuclei, the measurements improve the laboratory upper bound on the product gsgp(n) by 2 orders of magnitude for distances near 1 mm. The sensitivity of this technique can be increased by at least two more orders of magnitude.

19.
J Neurooncol ; 114(2): 209-18, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23748573

RESUMO

The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.


Assuntos
Condrossarcoma/cirurgia , Radiocirurgia/métodos , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Condrossarcoma/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Neoplasias da Base do Crânio/patologia , Neoplasias da Coluna Vertebral/patologia , Resultado do Tratamento , Carga Tumoral
20.
Avian Dis ; 57(2): 188-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24689172

RESUMO

Coccidiosis remains a significant threat to the welfare of game farm-reared pheasants in the United States. Although lasalocid has been demonstrated to be effective against pheasant specific coccidia, information regarding its safety in this species is lacking. The purpose of this study was to gather data on the safety of lasalocid when fed to Chinese ring-necked pheasants at one, two, and three times the recommended high dose of lasalocid used for prevention of coccidiosis in other poultry at three times the normal treatment period. Pheasant chicks (approximately 1 day-old; n = 160) were randomly blocked by sex into four treatment groups and given their respective diets continuously for 6 wk. No significant differences were observed in overall feed consumption, weight gain, feed conversion rates, clinical pathology measurements, or tissue gross and histopathologic evaluations between controls and treatment groups associated with lasalocid administration. Based on the results of this study it appears that lasalocid fed at the recommended rate of 125 ppm is safe in Chinese ring-necked pheasants.


Assuntos
Coccidiose/veterinária , Coccidiostáticos/efeitos adversos , Galliformes , Lasalocida/efeitos adversos , Doenças das Aves Domésticas/tratamento farmacológico , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Coccidiose/tratamento farmacológico , Coccidiostáticos/uso terapêutico , Relação Dose-Resposta a Droga , Comportamento Alimentar/efeitos dos fármacos , Feminino , Lasalocida/uso terapêutico , Masculino , Aumento de Peso/efeitos dos fármacos
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