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1.
Microbiol Spectr ; 11(1): e0409222, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36688641

RESUMO

The test performance and potential clinical utility of the ePlex blood culture identification Gram-negative (BCID-GN) panel was evaluated relative to matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry on bacterial isolates and conventional antimicrobial susceptibility testing. The majority (106/108, 98.1%) of GN bacteria identified by MALDI were on the BCID-GN panel, and valid tests (107/108, 99.1%) yielded results on average 26.7 h earlier. For all valid tests with on-panel organisms, the positive percent agreement was 102/105 (97.2%) with 3 false negatives and the negative percent agreement was 105/105. Chart review (n = 98) showed that in conjunction with Gram stain results, negative pan-Gram-positive (GP) markers provided the opportunity to discontinue GP antibiotic coverage in 63/98 (64.3%) cases on average 26.2 h earlier. Only 8/12 (66.7%) Enterobacterales isolates with resistance to third-generation cephalosporins harbored the CTX-M gene. In contrast, 8/8 CTX-M+ samples yielded a resistant isolate. Detection of 1 Stenotrophomonas maltophilia (18 h), 1 OXA23/48+ Acinetobacter baumannii (52.4 h), and 3 CTX-M+ Enterobacterales isolates on ineffective treatment (47.1 h) and 1 on suboptimal therapy (72.6 h) would have additionally enabled early antimicrobial optimization in 6/98 (6.1%) patients. IMPORTANCE The GenMark Dx ePlex rapid blood culture diagnostic system enables earlier time to identification of antimicrobial-resistant Gram-negative bacteria causing bloodstream infections. Its ability to rule out Gram-positive bacteria enabled early discontinuation of unnecessary antibiotics in 63/98 (64.3%) cases on average 26.2 h earlier. Detection of bacteria harboring the CTX-M gene as well as early identification of highly resistant bacteria such as Stenotrophomonas maltophilia and Acinetobacter baumannii enabled optimization of ineffective therapy in 6/98 (6.1%) patients. Its implementation in clinical microbiology laboratories optimizes therapy and improves patient care.


Assuntos
Anti-Infecciosos , Bacteriemia , Humanos , Hemocultura , Bactérias , Bactérias Gram-Negativas/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Bacteriemia/microbiologia
2.
Diagn Microbiol Infect Dis ; 104(3): 115762, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35988351

RESUMO

The test performance and potential clinical utility of the ePlex® BCID Gram-Positive (GP) Panel was evaluated relative to MALDI-TOF mass spectrometry on bacterial isolates and traditional antimicrobial susceptibility testing. All GP bacteria (n = 100) in the study were represented on the panel including 50 common skin contaminants, and 7/7 coinfections. The positive percent agreement (PPA) was 97/97 with 2 false positives. Detection of vanA yielded a PPA of 4/4 and NPA of 9/9. mecA gene detection exhibited a PPA of 14/14 and NPA of 14/14 for S. aureus and a PPA of 31/32(97%) and NPA of 16/16 for CNS with 1 false negative. Chart reviews (n = 80) identified a mean 24.4h faster time to organism identification, 53.4h earlier optimization in 15(18.8%) patients based on AMR gene detection, 29.2h earlier optimization for 8(10%) patients infected with organisms, such as streptococci, with very low resistance rates, and 42.9h earlier discontinuation of antimicrobials for 14(17.5%) patients with contaminant cultures.


Assuntos
Bacteriemia , Hemocultura , Bacteriemia/microbiologia , Hemocultura/métodos , Bactérias Gram-Positivas/genética , Humanos , Staphylococcus aureus
3.
Aliment Pharmacol Ther ; 44(11-12): 1139-1151, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27696456

RESUMO

BACKGROUND: The accuracy of current endoscopic modalities for diagnosing cholangiocarcinoma in primary sclerosing cholangitis (PSC) is suboptimal. AIM: To evaluate the comparative effectiveness of endoscopic retrograde cholangiopancreatography (ERCP)-based modalities, independently or in combination, for the diagnosis of cholangiocarcinoma in patients with PSC-induced biliary strictures. METHODS: Searches of PubMed, EMBASE, Web of Science and the Cochrane Library databases were performed through December 2015. Measured outcomes included sensitivity and specificity of all diagnostic modalities independently or in combination. A bivariate model was used to compute the pooled sensitivity and specificity, and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). A logistic regression model was used to impute the incremental performance of combining two diagnostic tests. RESULTS: Twenty-one studies met inclusion criteria: 13 on bile duct brushing for cytology, 7 on fluorescence in situ hybridisation (FISH), 2 on probe-based confocal laser endomicroscopy, and 4 on single-operator cholangioscopy with targeted biopsies. Single-operator cholangioscopy with targeted biopsies was the most accurate diagnostic modality at 96% (95% CI, 94-97%). The pooled sensitivity and specificity of single-operator cholangioscopy for diagnosis of cholangiocarcinoma in patients with PSC was 65% (95% CI, 35-87%) and 97% (95% CI, 87-99%), respectively. The pooled diagnostic odds ratio to detect cholangiocarcinoma was 59 (95% CI, 10-341). CONCLUSIONS: Single-operator cholangioscopy with targeted biopsies appears to be the most accurate ERCP-based modality for diagnosing cholangiocarcinoma in primary sclerosing cholangitis. However, future large, well-designed comparative diagnostic studies are warranted to validate these findings.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares/patologia , Biópsia , Colangiocarcinoma/diagnóstico por imagem , Colangite Esclerosante/diagnóstico por imagem , Humanos , Hibridização in Situ Fluorescente , Microscopia Confocal
4.
Aliment Pharmacol Ther ; 44(10): 1090-1101, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27640785

RESUMO

BACKGROUND: Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal for those with ongoing viraemia and is associated with higher rates of allograft failure and death. However, the optimal timing of HCV treatment for patients awaiting transplant remains unclear. AIM: To evaluate the comparative cost-effectiveness of treating HCV pre-LT vs. post-LT (pre-emptive or after HCV recurrence). METHODS: A Markov state-transition model was created to simulate the progression of a cohort of HCV-genotype 1 or 4 cirrhotic patients from the time of transplant listing until death. We then used this model to study the cost-effectiveness of ledipasvir-sofosbuvir (LDV/SOF) with ribavirin for 12 weeks, administered for three separate treatment strategies: (i) pre-LT; (ii) post-LT preemptively prior to HCV recurrence; or (iii) post-LT after HCV recurrence. RESULTS: In the base-case analysis using a median model for end-stage liver disease (MELD) score <25 at the time of transplant, we found that pre-LT treatment of HCV led to more QALYs for fewer dollars compared to other strategies. Analysis limited to living donor LT recipients revealed that pre-LT treatment was also the most cost-effective strategy. When the analysis was repeated for MELD ≥25, decompensated disease (Child-Pugh class B or C), and hepatocellular carcinoma cases, preemptive post-LT strategy was more cost-effective. CONCLUSIONS: Treatment of HCV prior to liver transplantation appears to be the most cost-effective strategy for patients with a MELD score <25. For patients with a MELD ≥25 or decompensated cirrhosis, preemptive post-liver transplantation treatment before HCV recurrence is the most cost-effective strategy.


Assuntos
Hepatite C/economia , Transplante de Fígado/economia , Recidiva Local de Neoplasia/economia , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/economia , Carcinoma Hepatocelular/cirurgia , Análise Custo-Benefício , Progressão da Doença , Quimioterapia Combinada , Fluorenos/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/cirurgia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/economia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/economia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Anos de Vida Ajustados por Qualidade de Vida , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Estados Unidos
5.
J Membr Biol ; 211(3): 191-200, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17091213

RESUMO

The effect of lysophosphatidylcholine (LPC) on lipid vesicle fusion and leakage induced by influenza virus fusion peptides and the peptide interaction with lipid membranes were studied by using fluorescence spectroscopy and monolayer surface tension measurements. It was confirmed that the wild-type fusion peptide-induced vesicle fusion rate increased several-fold between pH 7 and 5, unlike a mutated peptide, in which valine residues were substituted for glutamic acid residues at positions 11 and 15. This mutated peptide exhibited a much greater ability to induce lipid vesicle fusion and leakage but in a less pH-dependent manner compared to the wild-type fusion peptide. The peptide-induced vesicle fusion and leakage were well correlated with the degree of interaction of these peptides with lipid membranes, as deduced from the rotational correlation time obtained for the peptide tryptophan fluorescence. Both vesicle fusion and leakage induced by the peptides were suppressed by LPC incorporated into lipid vesicle membranes in a concentration-dependent manner. The rotational correlation time associated with the peptide's tryptophan residue, which interacts with lipid membranes containing up to 25 mole % LPC, was virtually the same compared to lipid membranes without LPC, indicating that LPC-incorporated membrane did not affect the peptide interaction with the membrane. The adsorption of peptide onto a lipid monolayer also showed that the presence of LPC did not affect peptide adsorption.


Assuntos
Lisofosfatidilcolinas/farmacologia , Lipídeos de Membrana/metabolismo , Orthomyxoviridae/fisiologia , Proteínas Virais de Fusão/metabolismo , Adsorção/efeitos dos fármacos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/fisiologia , Fusão de Membrana/efeitos dos fármacos , Orthomyxoviridae/química , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacocinética , Fragmentos de Peptídeos/fisiologia , Ligação Proteica/efeitos dos fármacos , Tensão Superficial/efeitos dos fármacos , Lipossomas Unilamelares/metabolismo
6.
Perfusion ; 17(6): 441-6, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12470035

RESUMO

The use of hyperthermia as an adjunct to chemotherapy in the treatment of peritoneal carcinomatosis is a promising technique for patients who otherwise have a poor prognosis for survival. We, herein, report an overview and description of our technique for the safe conduct of this treatment. Included in these data are a total of 71 patients who underwent an intraoperative treatment with Mitomycin C at temperatures of 41-42 degrees C for a 90- to 120-min time period. The treatment protocol, perfusion system description, technical considerations, and potential complications are also included. The prognosis for intraabdominal carcinomatosis is poor with conventional treatments and modalities. We believe that the use of this technique offers a very positive clinical alternative for patients undergoing treatment for laparoscopic palliation of malignant ascites and/or surgical debulking for intraoperative treatment and prevention of metastasis.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Hipertermia Induzida , Mitomicina/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Cuidados Intraoperatórios , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias
7.
Ann Surg Oncol ; 8(9): 720-2, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11597013

RESUMO

BACKGROUND: Differentiation of parotid neoplasms from extraparotid upper cervical lesions is difficult by physical examination. The purpose of this report is to identify the role of office-based parotid ultrasound (US) in the evaluation of periauricular masses. METHODS: A prospective database including the results of physical examination, office-based US, and the corresponding pathology was reviewed. Soft-tissue US was performed with a 7.5-mHz parallel probe with biplanar imaging. RESULTS: Thirty-eight patients were evaluated over a 28-month period (mean age. 45 years; range, 23-78 years). US demonstrated a mass within the substance of the parotid (n = 23, 61%), outside the parotid (n = 11, 29%), or diffuse parotitis (n = 4, 10%). Intraparotid masses were preauricular (n = 14), postauricular (n = 5), or upper cervical (n = 4) and were solid (n = 22) or cystic (n = 1). Patients with solid intraparotid masses underwent superficial (n = 20) or total parotidectomy (n = 2). Benign (n = 19) and malignant (n = 3) solid parotid nodules had similar US features of hypoechogenicity with posterior enhancement. Indistinct margins were noted in 3 of 3 malignant lesions as well as 15 of 19 benign nodules (P = .9). Extraparotid masses were confirmed to be nodal disease on the basis of observation with resolution (n = 3), fine-needle aspiration (n = 6), or surgical removal (n = 2) (mean follow-up, 6 months). CONCLUSIONS: Surgical office-based parotid US can delineate the location of periauricular mass lesions relative to the parotid gland. Benign and malignant lesions have a similar sonographic appearance.


Assuntos
Glândula Parótida/diagnóstico por imagem , Neoplasias Parotídeas/diagnóstico por imagem , Adenolinfoma/diagnóstico por imagem , Adenolinfoma/patologia , Adenoma Pleomorfo/diagnóstico por imagem , Adenoma Pleomorfo/patologia , Adulto , Idoso , Biópsia por Agulha , Cistos/diagnóstico por imagem , Cistos/patologia , Humanos , Pessoa de Meia-Idade , Glândula Parótida/patologia , Neoplasias Parotídeas/patologia , Consultórios Médicos , Estudos Prospectivos , Ultrassonografia
8.
FASEB J ; 15(13): 2545-7, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11641263

RESUMO

Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis, apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining coordinated gene expression profiles but are also highly effective for molecularly "fingerprinting" diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious disease pathogenesis.


Assuntos
Perfilação da Expressão Gênica , Hepatopatias/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Animais , Apoptose/genética , Eosinófilos/patologia , Fibrose , Genótipo , Hidroxiprolina/metabolismo , Inflamação/etiologia , Inflamação/genética , Inflamação/mortalidade , Mediadores da Inflamação/metabolismo , Interleucina-10/deficiência , Interleucina-10/genética , Interleucina-12/deficiência , Interleucina-12/genética , Interleucina-4/deficiência , Interleucina-4/genética , Fígado/metabolismo , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/mortalidade , Macrófagos/patologia , Camundongos , Camundongos Knockout , Infiltração de Neutrófilos , Neutrófilos/patologia , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/complicações , Esquistossomose mansoni/parasitologia , Taxa de Sobrevida , Fatores de Tempo
9.
J Pain Symptom Manage ; 22(2): 657-67, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11495712

RESUMO

To explore medical students' views of assisted death practices in patient cases that describe different degrees and types of physical and mental suffering, an anonymous survey was administered to all students at one medical school. Respondents were asked about the acceptability of assisted death activities in five patient vignettes and withdrawal of life support in a sixth vignette. In the vignettes, actions were performed by four possible agents: the medical student personally; a referral physician; physicians in general; or non-physicians. Of 306 medical students, 166 (54%) participated. Respondents expressed opposition or uncertainty about assisted death practices in the five patient cases that illustrated severe forms of suffering which were secondary to amyotrophic lateral sclerosis, treatment-resistant depressive and somatoform disorders, antisocial and sexually violent behavior, or AIDS. Students supported the withdrawal of life support in the sixth vignette depicting exceptional futility secondary to AIDS. Students were especially opposed to their own involvement and to the participation of non-physicians in assisted death activities. Differences in views related to sex, religious beliefs, and personal philosophy were found. Medical students do not embrace assisted death practices, although they exhibit tolerance regarding the choices of medical colleagues. How these attributes of medical students will translate into future behaviors toward patients and peers remains uncertain. Medical educators must strive to understand the perspectives of physicians-in-training. Expanded, empirically informed education that is attuned to the attitudes of medical students may be helpful in fulfilling the responsibility of imparting optimal clinical care skills.


Assuntos
Estudantes de Medicina/psicologia , Suicídio Assistido , Adulto , Atitude do Pessoal de Saúde , Ética Médica , Feminino , Humanos , Masculino , Inquéritos e Questionários
10.
Oncology (Williston Park) ; 15(3): 303-8; discussion 311-4, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11301829

RESUMO

Despite advances in surgery, radiotherapy, and chemotherapy, survival of patients with squamous cell carcinoma of the head and neck has not significantly improved over the past 30 years. Locally recurrent or refractory disease is particularly difficult to treat. Repeat surgical resection and/or radiotherapy are often not possible, and long-term results for salvage chemotherapy are poor. Recent advances in gene therapy have been applied to recurrent squamous cell carcinoma of the head and neck. Many of these techniques are now in clinical trials and have shown some efficacy. This article discusses the techniques employed in gene therapy and summarizes the ongoing protocols that are currently being evaluated in clinical trials.


Assuntos
Carcinoma de Células Escamosas/terapia , Terapia Genética , Neoplasias de Cabeça e Pescoço/terapia , Adenoviridae , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ensaios Clínicos como Assunto , Genes Supressores de Tumor , Vetores Genéticos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Proteína Supressora de Tumor p53/genética
11.
J Clin Oncol ; 19(2): 289-98, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11208818

RESUMO

PURPOSE: To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 x 10(11) particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation. RESULTS: Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication > or = 22 days after injection. CONCLUSION: ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested.


Assuntos
Adenovírus Humanos , Carcinoma de Células Escamosas/terapia , Terapia Genética , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/terapia , Proteínas E1B de Adenovirus , Adenovírus Humanos/genética , Adenovírus Humanos/fisiologia , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genes p53 , Neoplasias de Cabeça e Pescoço/genética , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Testes de Neutralização , Indução de Remissão , Viremia , Replicação Viral
12.
Cancer Res ; 60(22): 6359-66, 2000 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11103798

RESUMO

ONYX-015 is an E1B-55kDa gene-deleted adenovirus engineered to selectively replicate in and lyse p53-deficient cancer cells. To evaluate the selectivity of ONYX-015 replication and cytopathic effects for the first time in humans, we carried out a Phase II clinical testing of intratumoral and peritumoral ONYX-015 injection in 37 patients with recurrent head and neck carcinoma. Patients received ONYX-015 at a daily dose of 1 x 10(10) plaque-forming units (pfu) via intratumoral injection for 5 days during week 1 of each 3-week cycle (n = 30; cohort A), or 1 x 10(10) pfu twice a day for 10 days during weeks 1 and 2 of each 3-week cycle. Posttreatment biopsies documented selective ONYX-015 presence and/or replication in the tumor tissue of 7 of 11 patients biopsied on days 5-14, but not in immediately adjacent normal tissue (0 of 11 patients; P = 0.01). Tissue destruction was also highly selective; significant tumor regression (>50%) occurred in 21% of evaluable patients, whereas no toxicity to injected normal peritumoral tissues was demonstrated. p53 mutant tumors were significantly more likely to undergo ONYX-015-induced necrosis (7 of 12) than were p53 wild-type tumors (0 of 7; P = 0.017). High neutralizing antibody titers did not prevent infection and/or replication within tumors. ONYX-015 is the first genetically engineered replication-competent virus to demonstrate selective intratumoral replication and necrosis in patients. This agent demonstrates the promise of replication-selective viruses as a novel therapeutic platform against cancer.


Assuntos
Adenovírus Humanos/fisiologia , Carcinoma de Células Escamosas/terapia , Genes p53/genética , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/terapia , Proteínas E1B de Adenovirus/genética , Adenovírus Humanos/genética , Idoso , Anticorpos Antineoplásicos/biossíntese , Anticorpos Antineoplásicos/sangue , Biópsia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Replicação Viral
13.
Arch Pathol Lab Med ; 124(10): 1485-95, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11035581

RESUMO

BACKGROUND: Forensic pathologists face difficult moral questions in their practices each day. Consistent ethical and legal guidelines for autopsy tissue use extending beyond usual clinical and legal imperatives have not been developed in this country. OBJECTIVE: To obtain the perceptions of medical examiners regarding the ethical acceptability of autopsy tissue use for research and education. METHOD: A written, self-report questionnaire was developed and piloted by a multidisciplinary team at the University of New Mexico, Albuquerque. All individuals who attended a platform presentation at the National Association of Medical Examiners Annual Meeting in September 1997 were invited to participate. RESULTS: Ninety-one individuals completed the survey (40% of all conference registrants and approximately 75% of presentation attendees). Sixty-three percent of respondents had encountered an ethical dilemma surrounding autopsy tissue use, and one third reported some professional ethics experience. Perspectives varied greatly concerning the ethical acceptability of using autopsy tissues to demonstrate or practice techniques (eg, intubation, brachial plexus dissection) and of fulfilling requests to supply varying kinds and quantities of tissues for research and education. Most respondents indicated that consent by family members was important in tissue use decisions. Respondents agreed on the importance of basic values in education and research, such as integrity, scientific or educational merit, and formal institutional approval of a project. Characteristics of the decedent did not influence decisions to release tissues, except when the individual had died from a mysterious or very rare illness. Attributes of medical examiners, with the exception of sex, also did not consistently predict responses. CONCLUSION: Significant diversity exists in beliefs among medical examiners regarding perceptions of the appropriate use of autopsy tissues for education and research. There is need for further inquiry and dialogue so that enduring policy solutions regarding human tissue use for education and research may be developed.


Assuntos
Atitude do Pessoal de Saúde , Autopsia/psicologia , Médicos Legistas , Educação de Graduação em Medicina , Ética Médica , Medicina Legal/métodos , Coleta de Tecidos e Órgãos , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa , Inquéritos e Questionários , Consentimento do Representante Legal
14.
Ann Surg Oncol ; 7(8): 588-92, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11005557

RESUMO

BACKGROUND: The E1-b attenuated adenovirus, ONYX-015 (Onyx Pharmaceuticals, Richmond, CA), has demonstrated antitumoral activity in patients with recurrent squamous cell carcinoma of the head and neck. This study evaluated the effects of intratumoral ONYX-015 injection combined with systemic chemotherapy. METHODS: Inclusion criteria included: (1) recurrent squamous cell carcinoma of the head and neck, not surgically salvageable, (2) target tumor amenable to direct injection, and (3) no prior chemotherapy for recurrent disease. Patients received ONYX-015 (10(10) plaque-forming units) intratumorally for 5 days, cisplatin (80 mg/m2) on day 1, and 5-fluorouracil (800-1000 mg/m2) on days 1-5. This cycle was repeated every 3 weeks. Serial physical examination and computed tomography were used to assess tumor size and treatment response. RESULTS: Fourteen patients were enrolled, and nine patients were evaluable for response at the time of enrollment. The mean age of the evaluable patients was 60.8 years (range, 46-71 years). Mean maximum tumor diameter was 4.8 cm (range, 1.9-10.5 cm). Treatment-related toxicity included nausea (n = 7, 77.8%), vomiting (n = 5, 55.6%), mucositis (n = 5, 55.6%), pain at the injection site (n = 5, 55.6%), constipation (n = 4, 44.4%), and fatigue (n = 4, 44.4%). Locoregional tumor control was obtained in all nine patients (100%) (mean observation time, 157 days). Complete clinical response was seen in three patients (33.3%), partial response was seen in three patients (33.3%), minor response was seen in one patient (11.1%), and two patients (22.2%) had stable disease. Median time to local progression of disease has not been reached (range, 35-356 days). CONCLUSIONS: ONYX-015 adenovirus plus systemic cisplatin and 5-fluorouracil provides antitumor activity and local tumor control in patients with recurrent squamous cell carcinoma of the head and neck. This novel treatment approach offers hope for patients with limited treatment alternatives and provides the foundation for a phase III clinical trial.


Assuntos
Adenovírus Humanos/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Terapia Genética/métodos , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/terapia , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Progressão da Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Deleção de Genes , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Indução de Remissão
15.
Am Surg ; 66(8): 751-5, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10966034

RESUMO

Thyroid adenoma is a common disease. If partial thyroidectomy is performed, postoperative suppression therapy is often given to avoid nodule development in the remaining thyroid. It is unclear whether this treatment is warranted. Patients who underwent a partial thyroidectomy with a histologic diagnosis of follicular thyroid adenoma from January 1985 until February 1998 were studied retrospectively. Patients were analyzed on the basis of postoperative therapy, new thyroid nodule growth, and costs. Seventy-six patients were identified with a recurrence rate of 4 per cent (3/76). Sixty-one per cent (46/76) were treated with postoperative thyroid suppression therapy, and no difference in new nodule development was noted with at least 6 months of follow-up (P = 0.274). No patients required reoperation. A large cost saving was shown for patients who were not treated with levothyroxine. We conclude that postoperative thyroid suppression may not be routinely indicated. A prospective, randomized study would be necessary to answer this question conclusively.


Assuntos
Adenoma/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/prevenção & controle , Tireoidectomia , California , Redução de Custos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Nódulo da Glândula Tireoide/economia , Tiroxina/uso terapêutico
16.
J Neuroimmunol ; 108(1-2): 112-21, 2000 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10900344

RESUMO

Mice homozygous for a germline deletion of the interferon-gamma gene (IFN-gamma (-/-)) were infected with the LP-BM5 (BM5) retrovirus mixture to determine if the inability to produce IFN-gamma reduces collateral CNS damage associated with chronic neuroinflammation. Virus burdens in spleens and brains of infected mice were comparable, but spatial memory deficits were manifested earlier and to a greater extent in BM5/IFN-gamma (-/-) mice. The mice with spatial memory deficits showed considerable degradation of axons and microtubules, along with apoptosis of striatal neurons. These lesions were accompanied by extensive infiltration of perivascular spaces and ventricles by iNOS-positive leukocytes, and a 17-fold increase in CSF glutamate levels. Despite high levels of VCAM and ICAM expression on cerebral vasculature endothelia, the serum levels of soluble ICAM-1 were significantly decreased in BM5/IFN-gamma (-/-) mice, which may contribute to the enhanced leukocyte infiltration and subsequent neuronal damage. These results suggest that the presence of IFN-gamma is necessary at some points in the inflammatory process to protect against neurodegeneration.


Assuntos
Encéfalo/fisiopatologia , Deleção de Genes , Interferon gama/fisiologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/virologia , Retroviridae/fisiologia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/virologia , Quimiotaxia de Leucócito , Endotélio Vascular/metabolismo , Feminino , Ácido Glutâmico/líquido cefalorraquidiano , Inflamação/imunologia , Inflamação/patologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/metabolismo , Interferon gama/genética , Interferon gama/imunologia , Leucócitos/enzimologia , Leucócitos/imunologia , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/fisiopatologia , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/patologia , Neurônios/patologia , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase Tipo II , Percepção Espacial/fisiologia , Baço/imunologia , Baço/patologia , Baço/virologia , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/metabolismo , Carga Viral
18.
Oncology (Williston Park) ; 14(6 Suppl 3): 15-20, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10887647

RESUMO

Hepatocellular carcinoma (HCC) is one of the world's most common cancers. It is closely associated with cirrhosis, especially that due to viral hepatitis. The incidences of viral hepatitis and HCC are rising steadily in the United States. When symptomatic, HCC is usually unresectable and associated with a median survival of less than 6 months. Nodular lesions of undetermined malignant potential are often found in cirrhotic, explanted livers. There appears to be a continuum of increasing malignant potential from regenerating nodules to dysplastic nodules and to HCC. Pathologic differentiation of high-grade dysplastic nodules from HCC is often difficult. Early diagnosis offers the best potential for curative intervention. Screening of high-risk patient populations using serum alpha-fetoprotein and ultrasound has been attempted but is hindered by low sensitivity and specificity. The multinodularity and vascular flow anomalies of the cirrhotic liver complicate imaging. However, recent advances in magnetic resonance imaging technology allow for more accurate examination of the liver. We review the current status of hepatic imaging techniques and the results of screening a high-risk population for HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Humanos
19.
Oncology (Williston Park) ; 14(6 Suppl 3): 29-36, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10887649

RESUMO

The management of hepatic tumors presents a challenging problem. The natural history of primary and metastatic liver lesions portends a poor prognosis. However, surgical resection and newer ablative techniques have had a great impact on cure rates. Unfortunately, the majority of newly diagnosed patients have surgically unresectable disease. Advances in hepatic imaging have improved the preoperative evaluation of malignant lesions and greatly assisted in selecting patients for surgical resection or other interventions. Currently, a number of modalities are available for the evaluation of hepatic tumors. This article provides an overview of some of the modalities currently in use, examines the role of iron oxide magnetic resonance imaging (MRI), and relates experience with its use at Baylor University Medical Center.


Assuntos
Compostos Férricos , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Proc (Bayl Univ Med Cent) ; 13(1): 11-3, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16389319

RESUMO

Recent international reports have suggested that an abnormal pancreatic and bile duct junction can influence the degree of pancreatic fluid regurgitation, resulting in an increased incidence of biliary tract malignancy. To confirm these reports, we retrospectively examined the anatomic relation at the pancreaticobiliary junction in all patients diagnosed with cholangiocarcinoma or gallbladder cancer at Baylor University Medical Center (BUMC) over a 10-year period. From 1989 to 1998, 82 patients with bile duct cancer were treated at BUMC. Adequate visualization of the pancreaticobiliary junction was accomplished in 29 patients (35%). Among these patients, an abnormal junction, with a common channel length of 8 to >15 mm, was noted in 13 patients (45%). Thus, this study confirms previous reports regarding the high incidence of an abnormal pancreaticobiliary junction in patients with bile duct cancer. A prospective effort to examine this anatomy and the length of the common channel should be encouraged to identify a potential high-risk group.

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