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1.
J Neurosurg Spine ; 32(2): 285-291, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653821

RESUMO

Pyoderma gangrenosum (PG) is a rare inflammatory dermatosis that is most often associated with inflammatory bowel disease, but which can occur as a pathergic reaction around surgical incisions. The authors report the case of a patient who developed postoperative PG over the course of several months after undergoing extensive spinal instrumentation between the T4 and iliac levels. This is only the second such case occurring after spine surgery to be reported. The authors additionally review the literature to characterize treatment approaches and outcomes for this condition. The case highlights a potentially severe adverse effect of surgery that can be difficult to recognize and causes delays in effective treatment. It also demonstrates the importance of multidisciplinary collaboration in the effective care of patients.

2.
Neurosurgery ; 85(5): E889-E899, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31062018

RESUMO

BACKGROUND: Some patients are diagnosed with asymptomatic meningioma(s) after undergoing a screening CT and MRI for minor ailments or postresection. OBJECTIVE: To help clinicians in decision making for treatment of asymptomatic meningiomas. METHODS: A single center retrospective cohort study of 117 patients with 122 tumors treated with Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden). Patients were followed with longitudinal imaging and clinical evaluations. Tumor volumetry and developments of new signs or symptoms after GKRS were the end points in the study. RESULTS: Median patient age at GKRS was 60 yr (range 21-86 yr) with a median clinical follow-up of 53 mo (range 20-252 mo). The median pre-GKRS tumor volume was 3.6 ± 3.8 cc (±standard deviation). Tumors were treated with a median margin dose of 14 ± 2 Gy. At last follow-up, median tumor volume was 2.5 ± 3.6 cc. Radiological progression-free survival (PFS) rates were 97% and 94.4% at 5 yr and 10 yr, respectively. Clinical PFS rates were 86% and 70% at 5 yr and 10 yr, respectively. Development of neurological complications was seen in 21 (18%) patients, and 11 (52%) of them had undergone surgical resection prior to GKRS. CONCLUSION: GKRS is a reasonable treatment strategy for asymptomatic meningiomas and compares favorably to natural history studies in terms of tumor control and neurological preservation. It results in relatively low morbidity in previously untreated meningiomas and serves as an appealing alternative treatment modality for recurrent meningiomas in asymptomatic patients.

3.
Infect Immun ; 87(1)2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30323024

RESUMO

Malaria is caused by the protozoan parasite Plasmodium, which undergoes a complex life cycle in a human host and a mosquito vector. The parasite's cyclic GMP (cGMP)-dependent protein kinase (PKG) is essential at multiple steps of the life cycle. Phosphoproteomic studies in Plasmodium falciparum erythrocytic stages and Plasmodium berghei ookinetes have identified proteolysis as a major biological pathway dependent on PKG activity. To further understand PKG's mechanism of action, we screened a yeast two-hybrid library for P. falciparum proteins that interact with P. falciparum PKG (PfPKG) and tested peptide libraries to identify its phosphorylation site preferences. Our data suggest that PfPKG has a distinct phosphorylation site and that PfPKG directly phosphorylates parasite RPT1, one of six AAA+ ATPases present in the 19S regulatory particle of the proteasome. PfPKG and RPT1 interact in vitro, and the interacting fragment of RPT1 carries a PfPKG consensus phosphorylation site; a peptide carrying this consensus site competes with the RPT1 fragment for binding to PfPKG and is efficiently phosphorylated by PfPKG. These data suggest that PfPKG's phosphorylation of RPT1 could contribute to its regulation of parasite proteolysis. We demonstrate that proteolysis plays an important role in a biological process known to require Plasmodium PKG: invasion by sporozoites of hepatocytes. A small-molecule inhibitor of proteasomal activity blocks sporozoite invasion in an additive manner when combined with a Plasmodium PKG-specific inhibitor. Mining the previously described parasite PKG-dependent phosphoproteomes using the consensus phosphorylation motif identified additional proteins that are likely to be direct substrates of the enzyme.


Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Plasmodium falciparum/enzimologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Mapeamento de Interação de Proteínas , Ligação Proteica , Subunidades Proteicas/metabolismo , Técnicas do Sistema de Duplo-Híbrido
4.
World Neurosurg ; 119: e874-e881, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30099184

RESUMO

OBJECTIVE: To assess outcomes and complications of stereotactic radiosurgery treatment for trigeminal schwannoma (TS). METHODS: A retrospective analysis was performed to describe the presentation and outcomes of patients undergoing Gamma Knife radiosurgery (GKRS) for TS. Clinical, radiographic, and stereotactic radiosurgery dose plans were reviewed. Descriptive statistics and univariate analysis were performed to identify factors associated with poor tumor control. RESULTS: A total of 22 patients with TS were treated with GKRS between 1990 and 2018. One patient had a history of neurofibromatosis type II. Of the study population, 81% underwent GKRS as a first-line treatment. The average tumor volume was 3.3 cm3 and the average margin treatment dose was 14.1 Gy. The median clinical and radiographic follow-up period were 18.5 and 27 months, respectively. Tumor control was achieved in 17 patients (77.3%). Symptomatic improvement was noted in 8 patients (42.1%). Tumor expansion was observed in 7 patients (31.8%) and was associated with poor tumor control at last follow-up (P < 0.05). Patients who developed transient tumor expansion had higher margin doses (14.9 ± 1.1 Gy) compared with patients who did not have expansion (13.6 ± 1.3 Gyk P < 0.05). CONCLUSIONS: GKRS provides effective control for most TS. Increased margin doses are associated with tumor expansion, which was a poor prognostic event associated with progression and clinical decline. Based on these results, combined with analysis of available data from other series of TS treated with GKRS, we believe that margin dose between 13 and 14 Gy offers a high probability of tumor control, yet minimizing risk of adverse radiation effects.


Assuntos
Neoplasias dos Nervos Cranianos/radioterapia , Neurilemoma/radioterapia , Radiocirurgia/métodos , Doenças do Nervo Trigêmeo/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Nervos Cranianos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologia , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento , Doenças do Nervo Trigêmeo/patologia , Carga Tumoral
5.
Transplant Proc ; 49(8): 1864-1869, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28923638

RESUMO

In patients with portal hypertension, ectopic varices can develop at any site along the gastrointestinal tract outside the classically described gastroesophageal location. Like esophageal variceal hemorrhage, bleeding from ectopic varices can be life-threatening. Diagnosis and treatment of ectopic varices can be challenging; to date, no effective treatment algorithm has been described. A systematic teamwork approach to diagnosing and treatment of ectopic varices is required to successfully manage hemorrhage from ectopic varices.


Assuntos
Algoritmos , Gerenciamento Clínico , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Hipertensão Portal/complicações , Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/etiologia , Humanos , Hipertensão Portal/terapia , Ligadura , Masculino , Pessoa de Meia-Idade
6.
Aliment Pharmacol Ther ; 46(7): 681-687, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28782118

RESUMO

BACKGROUND: Tissue transglutaminase (tTG) immunoglobulin A (IgA) testing is a sensitive adjunct to the diagnosis of coeliac disease. The threshold for positivity was developed for diagnosis, with negative results reported as below the reference value (<4 U/mL). AIM: To investigate if an undetectable (tTG IgA<1.2 U/mL) is more predictive of healing compared to patients with negative but detectable serology (1.2-3.9 U/mL). METHODS: We performed a retrospective study of 402 treated coeliac disease patients seen at the Mayo Clinic with negative tTG IgA values drawn within 1 month of duodenal biopsy between January 2009 and December 2015. The Corazza-Villanacci score was used to assess mucosal healing. The presence of gastrointestinal symptoms was also collected. Logistic regression was used to assess the relationship of clinical variables with a normal biopsy. RESULTS: Patients with undetectable titres more frequently had normal duodenal histology compared to patients with detectable tTG IgA levels (117/240 vs. 53/162; OR=1.96; 1.292, 2.961). Asymptomatic patients more frequently had normal duodenum as compared to symptomatic patients (88/163 vs. 82/239; OR=2.25; CI: 1.494, 3.377). Patients with undetectable serology and on a gluten-free diet for ≥2 years were more likely to have no villous atrophy compared to patients with detectable serology (148/192 vs. 55/88; OR=2.02; CI: 1.17, 3.49). CONCLUSION: In subjects recovering from coeliac disease with negative tTG IgA serology, an undetectable titre is associated with normal histology on follow-up biopsy.


Assuntos
Doença Celíaca/diagnóstico , Dieta Livre de Glúten , Proteínas de Ligação ao GTP/imunologia , Imunoglobulina A/sangue , Transglutaminases/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Membrana Mucosa , Estudos Retrospectivos , Cicatrização
8.
Atmos Environ (1994) ; 174: 214-226, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29456452

RESUMO

The objective of this research is to learn how the near-road gradient, in which NO2 and NOX (NO + NO2) concentrations are elevated, varies with changes in meteorological and traffic variables. Measurements of NO2 and NOX were obtained east of I-15 in Las Vegas and fit to functions whose slopes (dCNO2 /dx and dCNOX /dx, respectively) characterize the size of the near-road zone where NO2 and NOX concentrations from mobile sources on the highway are elevated. These metrics were used to learn about the near-road gradient by modeling dCNO2 /dx and dCNOX /dx as functions of meteorological variables (e.g., wind direction, wind speed), traffic (vehicle count), NOX concentration upwind of the road, and O3 concentration at two fixed-site ambient monitors. Generalized additive models (GAM) were used to model dCNO2 /dx and dCNOX /dx versus the independent variables because they allowed for nonlinearity of the variables being compared. When data from all wind directions were included in the analysis, variability in O3 concentration comprised the largest proportion of variability in dCNO2 /dx, followed by variability in wind direction. In a second analysis constrained to winds from the west, variability in O3 concentration remained the largest contributor to variability in dCNO2 /dx, but the relative contribution of variability in wind speed to variability in dCNO2 /dx increased relative to its contribution for the all-wind analysis. When data from all wind directions were analyzed, variability in wind direction was by far the largest contributor to variability in dCNOX /dx, with smaller contributions from hour of day and upwind NOX concentration. When only winds from the west were analyzed, variability in upwind NOX concentration, wind speed, hour of day, and traffic count all were associated with variability in dCNOX /dx. Increases in O3 concentration were associated with increased magnitude near-road dCNO2 /dx, possibly shrinking the zone of elevated concentrations occurring near roads. Wind direction parallel to the highway was also related to an increased magnitude of both dCNO2 /dx and dCNOX /dx, again likely shrinking the zone of elevated concentrations occurring near roads. Wind direction perpendicular to the road decreased the magnitude of dCNO2 /dx and dCNOX /dx and likely contributed to growth of the zone of elevated concentrations occurring near roads. Thus, variability in near-road concentrations is influenced by local meteorology and ambient O3 concentration.

9.
Respir Res ; 16: 96, 2015 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-26243289

RESUMO

BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency disease results from mutations in the A1AT gene. Controversy exists in regards to treatment of heterozygous carriers of the S and Z deficiency alleles. Quantitation of allelic expression has not been possible with standard laboratory methods. Here we show that the recently described method for liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of A1AT tryptic peptides can differentiate between mutated (S and Z) and wild-type (non-S and non-Z) proteins allowing for quantitation of circulating allelic expression in heterozygous patients. METHODS: Serum (244 M/M, 61 M/Z, and 63 M/S) was combined with isotopically labeled peptide standards, digested with trypsin, and quantitated by LC-MS/MS. Total and allele-specific A1AT quantitation was performed by comparison of peptide peak height ratios to a standard curve for each peptide. Linear regression was used to compare results and central 95(th) percentile intervals were calculated using parametric analysis. RESULTS: Quantitation of circulating wild-type A1AT based on the proteotypic and allelic (non-S and non-Z) peptides was validated in M/M patients. Proteotypic peptide concentrations correlated linearly with quantitation by non-Z and non-S peptides [slopes (Spearman correlation coefficient) of 1.09 (0.89) and 0.98 (0.80), respectively]. Allele-specific quantitation showed significant differences in wild-type protein expression in M/Z and M/S patients. Although average total A1AT concentration was lower for M/Z patients, the percentage of wild-type protein in M/Z patients was significantly higher at 82 % (55- > 95 %) compared to 63 % (43-83 %) for M/S heterozygotes. In a cohort of M/Z patients with sufficient total A1AT (≥80 mg/dL), half had insufficient wild-type protein that could have clinical implications for pulmonary dysfunction. CONCLUSIONS: For the first time, a method to quantitate A1AT allele protein expression is described. Given the wide range of circulating wild-type protein observed in heterozygous patients, this method has the potential to reveal correlations between allele concentration and development and/or severity of clinical symptoms.


Assuntos
Alelos , Heterozigoto , Deficiência de alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/sangue , Biomarcadores/sangue , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Espectrometria de Massas em Tandem/métodos , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genética
10.
Tech Coloproctol ; 18(1): 73-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23111401

RESUMO

Presacral bleeding is a dreaded complication of pelvic surgery. Rapid and effective control of such bleeding is important to avoid potentially life-threatening outcomes. Various methods for controlling presacral bleeding, all with only limited success, have been described in the literature. We report the alternative technique of using the argon beam coagulator (ABC) to control presacral bleeding. We demonstrate its efficacious use in both open surgery and a laparoscopic case. Our approach involved applying an argon beam at bone setting directly to the bleeders and using a "point and shoot" technique. We found that ABC is a simpler, equally effective and expeditious way of addressing presacral bleeding. To the best of our knowledge, there has been only one previously reported case in the literature of the use of ABC to control presacral bleeding.


Assuntos
Coagulação com Plasma de Argônio/métodos , Hemostasia Cirúrgica/métodos , Hemorragia Pós-Operatória/terapia , Região Sacrococcígea/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Região Sacrococcígea/irrigação sanguínea
11.
Tech Coloproctol ; 18(6): 607-10, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24352923

RESUMO

BACKGROUND: Transanal hemorrhoidal dearterialization (THD) is a recently developed procedure to minimize postoperative pain from hemorrhoidectomy. This technique utilizes Doppler signals to aid ligation of hemorrhoidal arteries followed by mucopexy of redundant mucosa if needed. The aim of the present study was to assess patient satisfaction after THD. METHODS: This is a retrospective cohort study of patients who underwent THD at three different sites from April 2007 through October 2010. All procedures were performed in ambulatory settings according to protocol. Telephone surveys were conducted after a minimum of 1-month follow-up to assess patients' satisfaction on a scale of 1-10. Patients were asked whether the procedure had alleviated their symptoms. Patients were asked to recall duration of pain and time from surgery to return to work. RESULTS: Between April 2007 and October 2010, 216 patients with grade III-IV hemorrhoids underwent THD. There were 165 males and 61 females. Average age was 52.2 ± 14.2 years. All patients were discharged the same day after meeting ambulatory surgery center discharge criteria. Postoperative difficulty urinating occurred in 37 (17 %) patients, and six of them required temporary urinary catheterization. Transitory postoperative bleeding was reported by 38 (18 %) patients. Transitory incontinence to stool and flatus occurred in 18 (9 %) and 16 patients (8 %), respectively. Pelvic muscle spasms occurred in 21 (10 %) patients. Median follow-up was 23 months (range 1-42 months) with 143 (66 %) having at least 9 months between procedure and interview. Mean patient satisfaction was 8.5 ± 0.7 (on a scale of 1-10 with 10 being the best), and 91.5 % of patients felt the procedure had "helped" them. Average number of days with discomfort was 6.7 ± 2.1. Patients returned to work after an average of 10.3 ± 3.2 days. Our study is limited by lack of long-term follow-up and by retrospective complication assessment. CONCLUSIONS: Patient satisfaction with THD performed in ambulatory settings is high. Our data support performance of this procedure in an ambulatory setting.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Hemorroidectomia/métodos , Hemorroidas/cirurgia , Satisfação do Paciente , Ultrassonografia de Intervenção , Feminino , Hemorroidas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Med Phys ; 39(6Part19): 3837, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28517080

RESUMO

PURPOSE: Intensity Modulated Neutron Radiotherapy (IMNRT) has been commissioned for clinical use. The number of allowable segments in IMNRT plans is limited by MLC speed. Quality and deliverability of static IMNRT treatment plans using the TG-119 test suite were evaluated to establish guidelines for the number of segments per plan. METHODS: Treatment plans were created and optimized to specified constraints for all cases in the TG-119 test suite using the Varian Eclipse TPS. A 4MV photon beam with similar penetration characteristics as the fast neutron beam was used as a surrogate for this optimization. Final dose calculations were performed using an in-house TPS commissioned for neutron dose calculations. Following optimization, MLC segments were created for three ranges of total plan complexity - very limited (15-23 segments), limited (24- 31 segments), and unlimited. Calculated DVHs were then compared for compliance with TG-119 dose constraints. The estimated time of delivery for plans in each range was calculated based on known delivery parameters. RESULTS: The prostate case passes all constraints for each complexity level. All other plans fail to meet at least one constraint for one or more of the complexity levels. For all cases combined, the very limited, limited, and unlimited complexity levels meet 16, 17, and 19 of 23 total dose constraints, respectively. The mean estimated delivery time for the very limited, limited, and unlimited plans is 34 minutes (range: 27-39), 40 minutes (range: 34-45), and 68 minutes (range: 53-81) respectively, neglecting any delay due to therapists entering the treatment room. CONCLUSION: IMNRT plan quality is limited by current MLC capabilities. IMNRT plans should be limited to 25 segments to ensure a reasonable treatment time of 45 minutes. Even with this small number of segments, we were able to meet most dose constraints set forth in TG-119.

15.
Med Phys ; 39(6Part7): 3679, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28519810

RESUMO

PURPOSE: Until recently the treatment verification for patients undergoing fast neutron therapy at our facility was accomplished through a combination of neutron beam portal films aligned with a graticule mounted on an orthronormal x-ray tube. To eliminate uncertainty with respect to the relative positions of the x-ray graticule and the therapy beam, we have developed a graticule which is placed in the neutron beam itself. METHODS: For a graticule to be visible on the portal film, the attenuation of the neutron beam by the graticule landmarks must be significantly greater than that of the material in which the landmarks are mounted. Various materials, thicknesses, and mounting points were tried to gain the largest contrast between the graticule landmarks and the mounting material. RESULTS: The final design involved 2 inch steel pins of 0.125 inch diameter captured between two parallel plates of 0.25 inch thick clear acrylic plastic. The distance between the two acrylic plates was 1.625 inches, held together at the perimeter with acrylic sidewall spacers. This allowed the majority of length of the steel pins to be surrounded by air. The pins were set 1 cm apart and mounted at angles parallel to the divergence of the beam dependent on their position within the array. The entire steel pin and acrylic plate assembly was mounted on an acrylic accessory tray to allow for graticule alignment. CONCLUSION: Despite the inherent difficulties in attenuating fast neutrons, our simple graticule design produces the required difference of attenuation between the arrays of landmarks and the mounting material. The graticule successfully provides an in-beam frame of reference for patient portal verification.

16.
Leukemia ; 24(8): 1498-505, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20520636

RESUMO

Elevated immunoglobulin free light chain (FLC) level and abnormal FLC ratio are commonly seen in multiple myeloma (MM) and have prognostic implications. We hypothesized that presence of immunoglobin heavy chain (IgH) translocations leads to unbalanced production of light chains and more extreme abnormalities of FLC, and may explain the prognostic value of FLC. We studied 314 patients with newly diagnosed MM enrolled in a phase III trial, in whom results of fluorescence in situ hybridization testing and data on serum FLC levels were available. Cytogenetic analyses and FLC estimates were performed on stored samples and results were correlated with clinical data. The median ratio (FLC ratio) and the absolute difference (FLC diff) between the involved and uninvolved FLC were higher among those with IgH translocations, especially t(14;16). In multivariate analysis, the prognostic value of FLC estimates on progression-free and overall survival were independent of high-risk IgH translocations t(4;14) and t(14;16). A combination of the risk factors; either abnormal FLC estimate and/or the presence of high-risk IgH translocation, achieved better prognostic stratification. We conclude that patients with IgH translocations have higher FLC levels and abnormal ratios, but the prognostic effect of FLC is only partially explained by translocation status. A system including both these risk factors allows better prediction of outcome.


Assuntos
Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/genética , Translocação Genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Hibridização in Situ Fluorescente , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Prognóstico , Análise de Sobrevida
17.
Br J Anaesth ; 104(1): 16-22, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19933173

RESUMO

BACKGROUND: 'Open lung' ventilation is commonly used in patients with acute lung injury and has been shown to improve intraoperative oxygenation in obese patients undergoing laparoscopic surgery. The feasibility of an 'open lung' ventilatory strategy in elderly patients under general anaesthesia has not previously been assessed. METHODS: 'Open lung' ventilation (recruitment manoeuvres, tidal volume 6 ml kg(-1) predicted body weight, and 12 cm H(2)O PEEP) (RM group) was compared with conventional ventilation (no recruitment manoeuvres, tidal volume 10 ml kg(-1) predicted body weight, and zero end-expiratory pressure) in elderly patients (>65 yr) undergoing major open abdominal surgery with regard to oxygenation, respiratory system mechanics, and haemodynamic stability. We also monitored the serum levels of the interleukins (IL)-6 and IL-8 before and after surgery to determine whether the systemic inflammatory response to surgery depends on the ventilatory strategy used. RESULTS: Twenty patients were included in each group. The RM group tolerated open lung ventilation without significant haemodynamic instability. Intraoperative Pa(o(2)) improved in the RM group (P<0.01) and deteriorated in controls (P=0.01), but postoperative Pa(o(2)) was similar in both groups. The RM group had improved breathing mechanics as evidenced by increased dynamic compliance (36%) and decreased airway resistance (21%). Both IL-6 and IL-8 significantly increased after surgery, but the magnitude of increase did not differ between the groups. CONCLUSIONS: A lung recruitment strategy in elderly patients is well tolerated and improves intraoperative oxygenation and lung mechanics during laparotomy.


Assuntos
Abdome/cirurgia , Anestesia Geral/métodos , Respiração Artificial/métodos , Idoso , Idoso de 80 Anos ou mais , Resistência das Vias Respiratórias , Dióxido de Carbono/sangue , Feminino , Hemodinâmica , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Oxigênio/sangue , Pressão Parcial , Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias
18.
J Clin Lab Anal ; 23(6): 394-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19927349

RESUMO

Clozapine is indicated for the treatment of schizophrenia and related psychotic disorders. Several methods have been developed for monitoring Clozapine levels; however, they possess limited specificity and are often laborious. This study describes a simple liquid chromatography/tandem mass spectrometer (LCMS) method in human serum. The ion transitions monitored were m/z 327, 270, 296 for Clozapine, m/z 313, 192, 227 for Norclozapine and m/z 328, 271 for Loxapine. The assay is linear (25-1000 ng/ml) and showed a good correlation (r=0.98) within the analytical range of 79-1210 ng/ml in human serum. This assay is highly specific and sensitive for the simultaneous measurements of Clozapine and Norclozapine. The simplification of this assay makes it ideal for high throughput analyses of the patient samples in a routine clinical laboratory staffed with general medical technologists.


Assuntos
Cromatografia Líquida/métodos , Clozapina/análogos & derivados , Clozapina/sangue , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão , Clozapina/uso terapêutico , Humanos , Loxapina/sangue , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Espectrometria de Massas por Ionização por Electrospray
19.
Minerva Gastroenterol Dietol ; 54(4): 389-405, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19047980

RESUMO

Autoimmune pancreatitis (AIP) is a relatively rare but clinically important form of chronic pancreatitis that has typical clinical, serologic, histologic, and radiologic findings. Patients frequently present with jaundice and cholestatic serum liver function tests. The serum IgG4 level is typically elevated with a lymphoplasmacytic infiltrate in affected tissue that stains by immunohistochemistry for IgG4-containing cells. Characteristic radiologic features include pancreatomegally and pancreatobiliary duct strictures. Extrapancreatic manifestations are increasingly being recognized. AIP typically rapidly responds to corticosteroid therapy and possibly other immunosuppressive medications. A missed diagnosis can result in unnecessary pancreatic surgery with unnecessary morbidity and mortality. Although significant progress in disease pathophysiology has occurred during the past decade, there is still much to learn regarding disease pathogenesis and management. With further research, the diagnostic algorithm, treatment strategy, follow-up protocol, and long-term prognosis should become better defined.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Pancreatite/diagnóstico , Pancreatite/terapia , Diagnóstico Diferencial , Humanos , Pancreatite/imunologia
20.
Cell Cycle ; 7(18): 2894-901, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18787396

RESUMO

It is well established that B-Raf signaling through the MAP kinase (ERK) pathways plays a prominent role in regulating cell proliferation but how it does this is not completely understood. Here, we show that B-Raf serves a physiological role during mitosis in human somatic cells. Knockdown of B-Raf using short interfering RNA (siRNA) resulted in pleiotropic spindle abnormalities and misaligned chromosomes in over 80% of the mitotic cells analyzed. A second B-Raf siRNA gave similar results suggesting these effects are specific to downregulating B-Raf protein. In agreement with these findings, a portion of B-Raf was detected at the spindle structures including the spindle poles and kinetochores. Knockdown of C-Raf (Raf-1) had no detectable effects on spindle formation or chromosome alignment. Activation of the spindle assembly checkpoint was found to be dependent on B-Raf as evident by the inability of checkpoint proteins Bub1 and Mad2 to localize to unattached kinetochores in HeLa cells treated with B-Raf siRNA. Consistent with this, live-cell imaging microscopy showed that B-Raf-depleted cells exited mitosis earlier than control non-depleted cells. Finally, we provide evidence that B-Raf signaling promotes phosphorylation and kinetochore localization of the mitotic checkpoint kinase Mps1. Blocking B-Raf expression, ERK activity, or phosphorylation at Ser-821 residue perturbed Mps1 localization at unattached kinetochores. Thus, our data implicates a mitotic role for B-Raf in regulating spindle formation and the spindle checkpoint in human somatic cells.


Assuntos
Fibroblastos/citologia , Fibroblastos/enzimologia , Mitose , Proteínas Proto-Oncogênicas B-raf/deficiência , Fuso Acromático/enzimologia , Proteínas de Ciclo Celular/metabolismo , Cromossomos Humanos/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HeLa , Humanos , Cinetocoros/enzimologia , Mutação/genética , Fosfoproteínas/metabolismo , Fosforilação , Transporte Proteico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-raf/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
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