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1.
Eur Rev Med Pharmacol Sci ; 25(16): 5310-5317, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34486707

RESUMO

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. PATIENTS AND METHODS: This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). RESULTS: During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.


Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Palonossetrom/uso terapêutico , Piridinas/uso terapêutico , Idoso , Antieméticos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , COVID-19 , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/prevenção & controle , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Palonossetrom/administração & dosagem , Pandemias , Estudos Prospectivos , Piridinas/administração & dosagem , Vômito/prevenção & controle
2.
Scand J Surg ; 109(2): 133-142, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30654730

RESUMO

BACKGROUND AND AIMS: Primary aldosteronism is a common cause of secondary hypertension. Primary aldosteronism is caused by an aldosterone-producing adenoma or bilateral hyperplasia that in some cases is asymmetrical with one adrenal dominating aldosterone secretion. Most patients with aldosterone-producing adenoma are biochemically cured by unilateral adrenalectomy, but patients with bilateral hyperplasia have a significant risk of residual or recurrent disease. Here, immunohistochemistry of CYP11B1 and B2 was used to investigate whether these markers could aid in the diagnostic workup of primary aldosteronism patients. MATERIALS AND METHODS: A total of 39 patients with primary aldosteronism who underwent unilateral adrenalectomy for a presumed adenoma during 2013-2016 were included. Immunohistochemistry using monoclonal antibodies identifying the enzymes CYP11B1 and B2 was part of routine histopathological workup in 6 cases; in 33 cases, it was applied retrospectively. The hyperplasia diagnosis was suggested when there was no dominating nodule but immunoreactivity for CYP11B2 was seen in several nodules, which were also seen on routine sections. To distinguish between adenoma and hyperplasia, a ratio between the largest and second largest CYP11B2-positive nodules was calculated. RESULTS: In all, 22 patients had an aldosterone-producing adenoma, while 13 patients were judged to have hyperplasia. In four cases, a final diagnosis could not be established, thus these were judged equivocal. Among the 33 cases investigated retrospectively, the primary histopathological diagnosis was altered from hyperplasia to aldosterone-producing adenoma in 9 cases (27%) after immunohistochemistry, and the immunohistochemically rectified adenoma group displayed improved clinical cure rates compared to the routine H&E-diagnosed cohort. Moreover, the B2 ratio was significantly higher in adenoma than in hyperplasia and equivocal cases. CONCLUSION: Immunohistochemistry detecting CYP11B1 and B2 expression is of great help in establishing a final histopathological diagnosis in patients with primary aldosteronism. This procedure should be part of the histopathological routine in all operated primary aldosteronism patients.


Assuntos
Citocromo P-450 CYP11B2/sangue , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Imuno-Histoquímica/métodos , Esteroide 11-beta-Hidroxilase/sangue , Adenoma/sangue , Adenoma/metabolismo , Adenoma/cirurgia , Adrenalectomia , Adulto , Assistência ao Convalescente , Idoso , Aldosterona/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Citocromo P-450 CYP11B2/biossíntese , Feminino , Humanos , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/cirurgia , Hiperplasia/sangue , Hiperplasia/metabolismo , Hiperplasia/cirurgia , Masculino , Pessoa de Meia-Idade , Esteroide 11-beta-Hidroxilase/biossíntese
3.
Ann Chir Plast Esthet ; 60(2): 148-52, 2015 Apr.
Artigo em Francês | MEDLINE | ID: mdl-25001415

RESUMO

We report the case of a 55-year-old woman suffering from a type I neurofibromatosis (also known as Von Recklinghausen neurofibromatosis) who was diagnosed with a high-grade schwannosarcoma of the median nerve, between the upper third and the medium third of the arm, upon contact with the humerus, invading the humeral vessels. The oncologic treatment of this tumour consisted in the amputation of the arm through the surgical neck of the humerus. In order to create a laterothoracic claw, to bring a partial function of the upper limb back, we decided to realize a free fillet forearm flap. This composite flap was composed of the radius and the ulna, all the forearm muscles and the skin of the anterior side of the forearm. A humeroradial plate osteosynthesis was done and the flap was then harvested with the radial pedicle, and anastomosed to the axillar artery. This procedure gave our patient a functional stump, giving back the arm functionality, especially the claw movement.


Assuntos
Amputação Cirúrgica , Retalhos de Tecido Biológico/transplante , Nervo Mediano/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Neurilemoma/cirurgia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Sarcoma/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Neurilemoma/patologia , Neurofibromatose 1/complicações , Neoplasias do Sistema Nervoso Periférico/patologia , Sarcoma/patologia
5.
Ann Chir Plast Esthet ; 57(5): 423-49, 2012 Oct.
Artigo em Francês | MEDLINE | ID: mdl-22959952

RESUMO

UNLABELLED: We present in this original article a histological study of surgical skin residues. AIM OF THE STUDY: This study was realized in order to show, in objective way, skin diversity according to sex, age and area, and to illustrate some current surgical practices of our speciality. PATIENTS AND METHOD: Two years along, 141 patients was selected, 69 Men and 72 women. Fifty-four biopsies were realized on the upper extremity, 34 on the trunk and 53 on legs and arms. The histological study was based on two steps; the first one was a classic quantitative study, with measurement of each cutaneous layer, and objective evaluation of elastic density in superficial dermis. The second one was a descriptive histological analysis of each cutaneous area. RESULTS: The results coming from the quantitative analysis, allowed us to establish a classification of all the areas, according to each parameter. These results are globally compliant to the literature. The results of the descriptive analysis, lead us to conclude that it exists a lot of different skins with regional specificities. Then the crossover of the two analyses allowed us to define good practices tricks, in order to choose the best reconstruction technique for each area. CONCLUSION: This study is just a rough draft of a dynamic skin cartography adapted to our surgery. But it allowed us to confirm our basic premise: it doesn't exist only one skin but many skins.


Assuntos
Pele/anatomia & histologia , Cirurgia Plástica , Fatores Etários , Anatomia Regional , Face/anatomia & histologia , Feminino , Humanos , Extremidade Inferior/anatomia & histologia , Masculino , Especificidade de Órgãos , Fatores Sexuais , Fenômenos Fisiológicos da Pele , Pigmentação da Pele , Tronco/anatomia & histologia , Extremidade Superior/anatomia & histologia
6.
Diabetes Metab ; 37(4): 336-42, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21377387

RESUMO

AIM: The present study investigates the interaction of TLR4 and RAGE with their respective ligands as inducers of the inflammatory markers IL-6 and TNF-α. Also, the reactivity of peripheral blood mononuclear cells (PBMNC) from type 2 diabetic (T2D) patients and non-diabetic healthy controls (ND) were comparatively studied. METHODS: Concentrations of IL-6 and TNF-α were measured by sandwich Elisa, using kits supplied by Assay Designs (Ann Arbor, MI, USA). PBMNC from T2D and ND were incubated in the presence or absence of LPS, anti-TLR4 or anti-RAGE for 72 hours at 37°C under 5% CO(2). The final volume was adjusted to 300 µL in DMEM supplemented with 10% fetal bovine serum. After incubation, the cells were centrifuged, the supernatant collected and the cytokines measured. RESULTS: PBMNC from T2D were more sensitive to innate immune stimulation with LPS and monoclonal agonist anti-TLR4 than were cells from ND. The actions of LPS, anti-TLR4 and anti-RAGE potentiated the production of IL-6 and TNF-α in both groups. The simultaneous activation of monoclonal anti-RAGE and anti-TLR4 suggests that both antibodies used different receptors on the cell surface, but converged on the same PBMNC signaling metabolic pathways. This simultaneous activation induced a higher production of IL-6 and TNF-α in PBMNC from the T2D patients than from the ND subjects. CONCLUSION: Our results clearly show an exacerbation of innate immunity in PBMNC with T2D that was possibly hyperglycaemia-induced. These data, when analyzed together, suggest the importance of innate immunity in the pathogenesis of T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor 4 Toll-Like/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Humanos , Interleucina-6/biossíntese , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/farmacologia , Pessoa de Meia-Idade , Receptor para Produtos Finais de Glicação Avançada/imunologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/biossíntese
7.
Radiol Med ; 115(8): 1267-78, 2010 Dec.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-20680499

RESUMO

PURPOSE: We report a preliminary evaluation of the performance of computed tomography colonography (CTC) systematically obtained before optical colonoscopy (OC) in subjects with positive faecal occult blood test (FOBT) within a population-based screening programme for colorectal cancer (CRC). MATERIALS AND METHODS: Seventy-nine subjects with positive FOBT from a regional screening programme were invited to perform same day CTC and OC. CTC was performed with standard bowel preparation. OC with segmental unblinding was the reference standard. A per-patient per-adenoma analysis was performed. RESULTS: Forty-nine of 79 subjects (62%) with positive FOBT adhered to the study and completed both examinations. Twenty-two (44.9%) of the 49 had a cancer or an adenoma ≥6 mm. Per-patient sensitivity, specificity, negative predictive value and positive predictive value for cancer or adenoma ≥6 mm were 95.5% (95%CI:77.2%-99.9%), 51.9% (95%CI:32.0%-71.3%), 93.3% (95%CI:68.1%-99.8%) and 61.8% (95%CI:43.6%-77.8%). CONCLUSIONS: In the setting of a FOBT-based screening programme for CRC, CTC showed a high sensitivity, but relatively low specificity and positive predictive value, for cancer and adenoma ≥6 mm. Probably performing CTC without faecal tagging as second line test after a positive FOBT is not a cost-effective strategy.


Assuntos
Colonografia Tomográfica Computadorizada/métodos , Neoplasias Colorretais/diagnóstico por imagem , Programas de Rastreamento , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Valor Preditivo dos Testes , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Sensibilidade e Especificidade
8.
J Endocrinol Invest ; 32(10): 810-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19564722

RESUMO

OBJECTIVE: Due to increased use of imaging techniques, adrenal incidentalomas are frequently detected. The majority are non-hyperfunctioning adrenocortical tumors. We have previously shown that expression of the gene CYP17, coding for the enzyme in the cortisol pathway, correlates with cortisol release from adrenocortical tumors in vitro. The aim of this study was to compare clinical data with mRNA expression of CYP17 and CYP11B1 in adrenocortical tumors from patients with and without Cushing's syndrome and to identify adrenal tumors that may cause subclinical Cushing's syndrome. DESIGN: A retrospective study of 34 patients undergoing adrenalectomy due to an adrenal tumor. METHODS: Clinical data were collected. In the adrenal gland the mRNA expression of the genes CYP17 and CYP11B1 was studied with in situ hybridisation technique. RESULTS: The median ratio of CYP17/CYP11B1 expression in tumors from patients with Cushing's syndrome was significantly higher than the median ratio in the non-hyperfunctioning tumors. Tumors from 2 patients with subclinical Cushing's syndrome had ratios within the upper range for non-hyperfunctioning tumors. CONCLUSIONS: The ratio between the expression of the genes CYP17 and CYP11B1 in tumors from patients with Cushing's syndrome is significantly higher than in the non-hyperfunctioning tumors. This indicates that 17alpha-hydroxylase is a major determinant of cortisol overproduction. The patients with subclinical Cushing's syndrome in this study are too few to draw any firm conclusions although the results suggest that subclinical Cushing's syndrome may be identified post-operatively with this method.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/metabolismo , Hidrocortisona/biossíntese , Esteroide 11-beta-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/genética , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/genética , Adrenalectomia , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/genética , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Aldosterona/sangue , Aldosterona/urina , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/genética , Síndrome de Cushing/metabolismo , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Hibridização In Situ , Achados Incidentais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Estudos Retrospectivos , Estatísticas não Paramétricas
9.
Scand J Surg ; 97(3): 248-53, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18812275

RESUMO

BACKGROUND AND AIMS: Differentiation between the two major subgroups of primary aldosteronism, bilateral hyperplasia and aldosterone producing adenoma is essential since therapy in the former is medical and in the latter surgical. The aim of the present study was to evaluate the clinical utility of adrenocortical scintigraphy in the management of primary aldosteronism. MATERIAL AND METHODS: [131I] norcholesterol (NP-59) scintigraphy with dexamethasone suppression for subclassification and lateralization of primary aldosteronism was evaluated in 49 patients with long-term follow-up after diagnosis and treatment. RESULTS: Thirty-three patients with the diagnosis of aldosterone producing adenoma were operated with adrenalectomy. Preoperative scintigraphy showed lateralized isotope uptake in 27/33 patients while 6 showed no uptake. Twenty-two were cured and three significantly improved. Thus, in 25/33 (76%), scintigraphy showed the correct side as the patients benefited of surgery. Two patients did not improve. Fourteen patients with a probable diagnosis of bilateral hyperplasia had normal scintigraphies. CONCLUSIONS: In the present retrospective study we found limited sensitivity of NP-59 scintigraphy. However, when a lateralized scintigraphic uptake is achieved it has a high accuracy. Scintigraphy may be used as an adjunct in cases where adrenal venous sampling is inconclusive.


Assuntos
Glândulas Suprarrenais/diagnóstico por imagem , Adrenalectomia/métodos , Hiperaldosteronismo/diagnóstico por imagem , Cuidados Pré-Operatórios/métodos , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Cintilografia , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
10.
Burns ; 32(8): 1028-31, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16982156

RESUMO

The use of pre-filled valveless gas canisters for lamps or camping stoves has caused a number of serious burn incidents. We performed a retrospective analysis of all of the patients who were victims of such incidents admitted to the Marseille Burn Centre between January 1990 and March 2004. There were a total of 21 patients burned in such conditions. Adult males made up the majority of the victims of this sort. Lesions were often extensive (60% of the patients were burned over more than 10% of their body surface) and systematically deep. In order of frequency, burn locations were: the lower limbs, the upper limbs, the hands and the face. The incidents principally occurred during replacement of the canister near an open flame. The marketing of a canister with a valve in order to avoid gas leaks did not cause the old canisters to be taken off the market. On the contrary, European Safety Standard EN417, updated in October 2003, validated the use of these valveless canisters. The severity of the lesions caused and the existence of safe equivalent products requires the passage of a law that forbids valveless canisters.


Assuntos
Queimaduras/etiologia , Acampamento/estatística & dados numéricos , Utensílios Domésticos/instrumentação , Adulto , Idoso , Utensílios de Alimentação e Culinária , Desenho de Equipamento , Feminino , Gases , Humanos , Iluminação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Br J Plast Surg ; 58(6): 859-61, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15950954

RESUMO

Hibernoma is a rare benign tumour of brown fat. In most cases it presents as a voluminous slow-growing mass in the regions where remnants of brown fat can remain in adults. We report a case of a hibernoma on the thigh and present the diagnostic and therapeutic elements of this type of tumour, whose differential diagnosis of liposarcoma.


Assuntos
Lipoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Lipoma/cirurgia , Lipossarcoma/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias de Tecidos Moles/cirurgia , Coxa da Perna , Tomografia Computadorizada por Raios X
12.
South Med J ; 94(3): 347-9, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11284527

RESUMO

Surgical drainage is the standard treatment for pancreatic pseudocysts and their complications. However, acute symptomatic pancreatic pseudocysts are amenable to endoscopic internal drainage in select cases. We report a case of pancreatic pseudocyst with biliary fistula resulting from a recurrent pseudocyst treated with endoscopic stent drainage.


Assuntos
Fístula Biliar/complicações , Endoscopia/métodos , Pseudocisto Pancreático/terapia , Diagnóstico Diferencial , Drenagem/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático/complicações , Pseudocisto Pancreático/diagnóstico , Recidiva , Stents , Tomografia Computadorizada por Raios X
13.
Am J Hematol ; 67(1): 20-6, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11279653

RESUMO

Syndecan-1 (CD138) is a cell membrane proteoglycan that binds extracellular matrix components and various growth factors. The role of syndecan-1 in the control of cell growth and morphology has been illustrated by its altered expression in hematological malignancies such as multiple myeloma as well as some solid tumors. It has been reported that the expression of syndecan-1 in cells of the B lineage is developmentally regulated such that pre-B cells and plasma cells express syndecan-1 while mature B cells do not. Thus, we investigated whether the proximal promoter region of the murine syndecan-1 promoter was able to confer the observed on-off-on expression of syndecan-1 in cells of the B lineage as they develop from pre-B cells to plasma cells. Experiments carried out using deletion mutants of the proximal promoter cloned upstream of the CAT reporter gene transfected into murine cell lines, representing the above stages of B-cell development, such as BA/F3 (pro-B cell), 70Z/3 (pre-B cell), 2PK3 (late mature B cell), and MPC-11 (plasma cell), showed detectable levels of CAT expression. The WEHI-231 (mature B cell) cell lines did not show detectable levels of CAT reporter activity. The strong levels of expression were observed with a fragment of the proximal promoter spanning the region from -365 to -95 (from the translation start point). However, Northern analysis of RNA obtained from the five murine B-cell lines, representing various stages of B-cell development, showed that the 70Z/3, MPC-11 but not BA/F3, and 2PK3 cells expressed detectable levels of syndecan-1 mRNA. By FACS analysis, using a rat anti mouse syndecan-1 antibody, syndecan-1 expression on the cell surface was found to correlate with the observed mRNA expression patterns in these cell lines. Our results indicate that the proximal promoter of the murine syndecan-1 promoter is not sufficient for the observed developmental pattern of syndecan expression in B cells.


Assuntos
Linfócitos B/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Regiões Promotoras Genéticas , Proteoglicanas/genética , Proteoglicanas/metabolismo , Animais , Linfócitos B/fisiologia , Sítios de Ligação , Northern Blotting , Linhagem Celular , Linhagem da Célula/genética , Citometria de Fluxo , Genes Reporter , Camundongos , Mutação , Plasmócitos/metabolismo , Plasmócitos/fisiologia , RNA/metabolismo , Fator de Transcrição Sp1/metabolismo , Sindecana-1 , Sindecanas , Transfecção
14.
Arch Biochem Biophys ; 377(2): 284-9, 2000 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-10845705

RESUMO

The two Cu,Zn superoxide dismutases from the amphibian Xenopus laevis (denoted XSODA and XSODB) display different heat sensitivities, XSODA being more thermolabile than XSODB. In this study, we have investigated the contribution of a free cysteine residue located close to the subunit interface of XSODA to its lower thermal stability. We have found that mutation of residue Cys 150 to Ala in XSODA makes the thermal stability of this enzyme comparable to that of the wild-type XSODB isoenzyme, while the introduction of a cysteine residue in the same position of XSODB renders this enzyme variant much more heat-sensitive. Differential scanning calorimetry experiments showed that XSODA has a melting temperature about 8.5 degrees C lower than that of XSODB. On the contrary, the melting temperature of XSODACys150Ala is very close to that of XSODB, while the melting temperature of XSODBSer150Cys is even lower than that of wild-type XSODA. These data indicate that the free cysteine residue present in XSODA affects not only the reversibility of unfolding of the enzyme but also its conformational stability. We suggest that the large effect of the Cys 150 residue on XSODA stability might be due to incorrect disulfide bond formation or disulfide bond interchange during heat-induced unfolding rather than to alteration of the interaction between the enzyme subunits.


Assuntos
Cisteína/metabolismo , Superóxido Dismutase/química , Animais , Varredura Diferencial de Calorimetria , Cisteína/química , Dimerização , Espectroscopia de Ressonância de Spin Eletrônica , Estabilidade Enzimática , Conformação Proteica , Temperatura , Termodinâmica , Fatores de Tempo , Xenopus laevis
16.
Ann Surg Oncol ; 7(2): 139-44, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10761793

RESUMO

BACKGROUND: Studies have shown that the survival of patients with gastric adenocarcinoma is related to the number of regional lymph nodes with metastases. The probability of identifying node-positive cancers increases with the number of lymph nodes resected and examined. It has been recommended that at least 15 lymph nodes be removed and examined for adequate staging. Prospective randomized studies have shown the lymph node yield is much greater with the D2 resection than the D1. This study evaluated the relative contribution of both the number of resected lymph nodes and the extent of gastric resection (D1/D2) on the outcome of patients with proximal gastric cancer. METHODS: The medical records of 114 patients with adenocarcinoma of the proximal stomach, who underwent a curative gastric resection, were reviewed. Patients were stratified into four groups, i.e., two groups, D1/D1.5 and D2/D2.5, based on the extent of resection, and two groups based on the number of lymph nodes removed, fewer than 15 lymph nodes and 15 or more lymph nodes. Survival was determined by the method of Kaplan-Meier and differences compared by the log-rank test. Multivariate analysis was performed by using the Cox model. RESULTS: The number of resected lymph nodes had no effect on the survival of the group as a whole. A significant improvement in survival was noted for patients with a D2 or greater resection. The median survival of patients with 15 or more lymph nodes resected improved from 25 months to 42 months when treated with an extended resection, (D2 or D2.5). Resection of 15 or more lymph nodes alone, or combined with an extended resection, resulted in a statistically significant improvement in survival for patients in American Joint Committee on Cancer Staging (AJCC) stage II. CONCLUSIONS: Both resection of 15 or more lymph nodes and extended lymphadenectomy contributed to the survival advantage observed in patients with AJCC stage II gastric cancer. The D2 gastric resection prolonged the median survival time and improved the 5-year survival rate for patients with 15 or more resected lymph nodes.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Gastrectomia , Excisão de Linfonodo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
17.
Surg Today ; 30(1): 94-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10648094

RESUMO

Metastasis to the pancreas from a distant primary cancer is uncommon, most cases being detected in the advanced stages of disease, often multiple in number, and diffusely displayed beyond surgical salvage. A solitary metastasis in the head of the pancreas is rarely encountered and although potentially amenable to surgical resection, surgeons are hesitant to perform pancreaticoduodenectomy for metastatic disease. Renal cell carcinoma is one malignancy with a propensity to metastasize to the pancreas. We report herein the case of a solitary pancreatic metastasis from renal cell carcinoma successfully treated by pancreaticoduodenectomy in a middle-aged man. A discussion on the indications and effectiveness of performing pancreaticoduodenectomy for metastatic renal cell carcinoma is also presented.


Assuntos
Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Neoplasias Pancreáticas/secundário , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade
18.
Obstet Gynecol ; 95(1): 147-50, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10636518

RESUMO

OBJECTIVE: To investigate the seroimmunologic (CD3, CD4, CD8 lymphocytes, C3c and C4 complement fractions, and several autoantibodies) and immunohistochemical (T lymphocyte subpopulations, B lymphocytes, natural killer cells, macrophages, immunoglobulin [Ig] G, Ig M, and C3c complement fraction) characteristics of vulvar lichen sclerosus. METHODS: Serum samples from 68 women with histologically proven lichen sclerosus were compared with those from 53 healthy controls, and tissue samples from 14 of 68 women chosen at random were compared with those from 14 of 53 healthy controls. A scoring system was constructed to compare the number of cells in the tissue. RESULTS: Patients had significantly lower counts of circulating lymphocytes CD3 and CD4 than controls (P < .05) and a higher number of autoantibodies (P < .01). Analysis of the tissue samples confirmed a lower number of CD2 cells (two-tailed P = .002 in epidermis, .005 in dermis), CD3 cells (two-tailed P = .001 in epidermis and in dermis), CD4 cells (two-tailed P = .002 in epidermis, .011 in dermis), and CD8 cells (two-tailed P = .002 in epidermis, .051 in dermis) in subjects than in controls. Numbers of monocyte-macrophage cells were similar in the epidermis but different in the dermis (two-tailed P = .003). No natural killer CD56 cells or B lymphocytes (CD19-CD21) were detected in the affected areas. Deposits of IgG, IgM, and C3 were no greater in biopsy specimens of patients than in those of controls. CONCLUSION: Vulvar lichen sclerosus is not caused by a T cell-mediated response, and a viral origin is unlikely. The absence of CD19 and CD21 cells excludes local production of autoantibodies. Our data do not confirm an autoimmune pathogenesis for vulvar lichen sclerosus but help explain why systemic cortisone is of no benefit and justify the use of petroleum jelly to relieve pruritus.


Assuntos
Líquen Escleroso e Atrófico/imunologia , Linfócitos T/imunologia , Doenças da Vulva/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoimunidade , Feminino , Humanos , Imunidade Celular , Imuno-Histoquímica , Células Matadoras Naturais/imunologia , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia
19.
J Biomater Sci Polym Ed ; 10(6): 641-55, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10385225

RESUMO

In membrane hybrid liver support devices (HLSDs) using isolated hepatocytes where oxygen is transported only by diffusion to the cells, about 15-40% of the cell mass is likely to be in direct contact with the semipermeable membranes used as immunoselective barriers: quantitative effects of membrane surface properties on the kinetics of hepatocyte metabolic reactions may also affect HLSD performance. In this paper, we report our investigation of the effects of surface morphology of two microporous commercial membranes on the kinetics of oxygen consumption and ammonia elimination by primary hepatocytes in adhesion culture. Isolated rat hepatocytes were cultured on polypropylene microporous membranes with different surface roughness and pore size in a continuous-flow bioreactor whose fluid dynamics was optimized for the kinetic characterization of liver cell metabolic reactions. Collagen-coated membranes were used as the reference substratum. Hepatocyte adhesion was not significantly affected by membrane surface morphology. The rates of the investigated reactions increased with ammonia concentration according to saturation kinetics: the values of kinetic parameters Vmax and K(M) increased as cells were cultured on the membrane with the greatest membrane surface roughness and pore size. For the reaction of oxygen consumption, Vmax increased from 0.066 to 0.1 pmol h(-1) per cell as surface roughness increased from 70 to 370 nm. For the kinetics of ammonia elimination. K(M) increased from 0.23 to 0.32 mM and Vmax increased from 1.49 to 1.79 pmol h(-1) per cell with membrane surface roughness increasing from 70 to 370 nm. Cells cultured on collagen-coated membranes consistently yielded the highest reaction rates. The Vmax values of 0.18 and 2.84 pmol h(-1) per cell for oxygen consumption and ammonia elimination, respectively, suggest that cell functions are also affected by the chemical nature of the substratum.


Assuntos
Amônia/metabolismo , Adesão Celular , Fígado/metabolismo , Membranas Artificiais , Consumo de Oxigênio , Animais , Reatores Biológicos , Células Cultivadas , Relação Dose-Resposta a Droga , Cinética , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar
20.
J Surg Res ; 84(2): 157-61, 1999 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10357913

RESUMO

BACKGROUND: Although the liver is a potent tumor cell killing organ it is frequently the site of lethal metastases often signifying the endstage for patients with colorectal cancers. Enhancing hepatic-associated immunity remains elusive until the interactions among hepatic nonparenchymal cells (NPC) are deciphered. We sought to modulate the cellular components of the hepatic immune system of mice with anti-NK and anti-T-cell-neutralizing antibodies in order to determine the cell type most efficacious in preventing liver metastasis. MATERIALS AND METHODS: Liver-derived murine colon adenocarcinoma (LD-MCA-38) cells were injected into the ileocolic vein (ICV) of immunocompetent and immunodeficient C57BL/6 mice. Mice were pretreated 1 day prior to tumor cell injection with one of three antibodies: anti-AsGM1, Anti-NK1.1, or Anti-Thy1.2. On Day 21 laparotomy was performed to determine the extent of hepatic tumor foci. The number of hepatic tumor foci was recorded and compared by the Wilcoxon rank sum test. RESULTS: Mice pretreated with anti-AsGM1 or Anti-NK1.1 developed a massive increase in the number of hepatic tumor foci and decreased survival compared to the control treated mice. Pretreatment with anti-Thy1.2 antibody resulted in a significant decrease in the number of hepatic tumor foci. LD-MCA-38 tumor cells were unable to colonize the liver of C57BL/6 athymic nude mice; however, anti-AsGM1 antibody abolished this antimetastatic effect. There was no difference in the extent of hepatic metastasis and survival between immunodeficient C57BL/6 bg/bg and their conventional littermates bg/+. CONCLUSION: AsGM1+ NK cells exhibit a significant antitumor response in the absence of T-cells. The concept of stimulating NK cell activity and suppressing T-cell function may enhance liver-associated immunity and serve as a deterrent for blood-borne tumor cells metastasizing to the liver.


Assuntos
Adenocarcinoma/prevenção & controle , Neoplasias do Colo/patologia , Gangliosídeo G(M1)/metabolismo , Células Matadoras Naturais/fisiologia , Neoplasias Hepáticas/prevenção & controle , Adenocarcinoma/secundário , Animais , Anticorpos/farmacologia , Anticorpos Monoclonais/farmacologia , Antígenos/imunologia , Antígenos Ly , Antígenos de Superfície , Gangliosídeo G(M1)/imunologia , Imunocompetência/fisiologia , Células Matadoras Naturais/metabolismo , Lectinas Tipo C , Neoplasias Hepáticas/secundário , Contagem de Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL/genética , Camundongos Nus/imunologia , Subfamília B de Receptores Semelhantes a Lectina de Células NK , Invasividade Neoplásica/prevenção & controle , Transplante de Neoplasias , Proteínas/imunologia , Linfócitos T/patologia , Antígenos Thy-1/imunologia , Células Tumorais Cultivadas
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