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1.
ESMO Open ; 7(1): 100356, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34953400

RESUMO

BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Paclitaxel , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Projetos Piloto , Gencitabina
2.
Water Sci Technol ; 80(4): 675-684, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31661447

RESUMO

Microbial processes are critical to the function of freshwater ecosystems, yet we still do not fully understand the factors that shape freshwater microbial communities. Furthermore, freshwater ecosystems are particularly susceptible to effects of environmental change, including influx of exogenous nutrients such as nitrogen and phosphorus. To evaluate the impact of nitrogen loading on the microbial community structure of shallow freshwater lakes, water samples collected from Lake Shenandoah (Virginia, USA) were incubated with two concentrations of either ammonium, nitrate, or urea as a nitrogen source. The potential impact of these nitrogen compounds on the bacterial community structure was assessed via 16S rRNA amplicon sequencing. At the phylum level, the dominant taxa in Lake Shenandoah were comprised of Actinobacteria and Proteobacteria, which were not affected by exposure to the various nitrogen treatments. Overall, there was not a significant shift in the diversity of the bacterial community of Lake Shenandoah with the addition of nitrogen sources, indicating this shallow system may be constrained by other environmental factors.


Assuntos
Lagos , Nitrogênio , Bactérias , Proteobactérias , RNA Ribossômico 16S
3.
Am J Transplant ; 14(6): 1328-33, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24726020

RESUMO

Invasive mold infections (IMIs) are a major source of morbidity and mortality among lung transplant recipients (LTRs), yet information regarding the epidemiology of IMI in this population is limited. From 2001 to 2006, multicenter prospective surveillance for IMIs among LTR was conducted by the Transplant-Associated Infection Surveillance Network. The epidemiology of IMI among all LTRs in the cohort is reported. Twelve percent (143/1173) of LTRs under surveillance at 15 US centers developed IMI infections. The 12-month cumulative incidence of IMIs was 5.5%; 3-month all-cause mortality was 21.7%. Aspergillus caused the majority (72.7%)of IMIs; non-Aspergillus infections (39, 27.3%) included Scedosporium (5, 3.5%), mucormycosis (3, 2.1%) and "unspecified" or "other" mold infections (31, 21.7%). Late-onset IMI was common: 52% occurred within 1 year posttransplant (median 11 months, range 0-162 months). IMIs are common late-onset complications with substantial mortality in LTRs. LTRs should be monitored for late-onset IMIs and prophylactic agents should be optimized based on likely pathogen.


Assuntos
Pneumopatias/epidemiologia , Transplante de Pulmão , Micoses/epidemiologia , Estudos de Coortes , Humanos , Pneumopatias/microbiologia , Micoses/microbiologia
4.
Curr Med Chem ; 21(15): 1668-78, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24083603

RESUMO

Glycolysis is an important metabolic pathway for most organisms, including protozoan parasites. Many of these primitive eukaryotes have streamlined their metabolism, favoring glycolysis for generating ATP in the glucose-rich environments in which they reside. Therefore, the enzymes involved in hexose metabolism could prove to be attractive targets for therapeutic development. This hypothesis is supported by a number of chemical and genetic validation studies. Additionally, the peculiar biochemistry of many of the components, along with limited protein sequence identity emphasizes the likelihood of developing compounds that selectively inhibit the parasite enzymes. In this review, we examine the status of target validation at the genetic and/or chemical levels from the protozoan parasites. While the proteins from some species have been interrogated to the point that well-defined lead compounds have been identified with activities against both enzyme and parasite growth, progress in other systems has to date been limited.


Assuntos
Antiprotozoários/farmacologia , Proteínas de Protozoários/metabolismo , Animais , Glicólise , Humanos , Terapia de Alvo Molecular
5.
Bone ; 46(4): 1138-45, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20044046

RESUMO

Type 2 diabetes is associated with normal-to-higher bone mineral density (BMD) and increased rate of fracture. Hyperinsulinemia and hyperglycemia may affect bone mass and quality in the diabetic skeleton. In order to dissect the effect of hyperinsulinemia from the hyperglycemic impact on bone homeostasis, we have analyzed L-SACC1 mice, a murine model of impaired insulin clearance in liver causing hyperinsulinemia and insulin resistance without fasting hyperglycemia. Adult L-SACC1 mice exhibit significantly higher trabecular and cortical bone mass, attenuated bone formation as measured by dynamic histomorphometry, and reduced number of osteoclasts. Serum levels of bone formation (BALP) and bone resorption markers (TRAP5b and CTX) are decreased by approximately 50%. The L-SACC1 mutation in the liver affects myeloid cell lineage allocation in the bone marrow: the (CD3(-)CD11b(-)CD45R(-)) population of osteoclast progenitors is decreased by 40% and the number of (CD3(-)CD11b(-)CD45R(+)) B-cell progenitors is increased by 60%. L-SACC1 osteoclasts express lower levels of c-fos and RANK and their differentiation is impaired. In vitro analysis corroborated a negative effect of insulin on osteoclast recruitment, maturation and the expression levels of c-fos and RANK transcripts. Although bone formation is decreased in L-SACC1 mice, the differentiation potential and expression of the osteoblast-specific gene markers in L-SACC1-derived mesenchymal stem cells (MSC) remain unchanged as compared to the WT. Interestingly, however, MSC from L-SACC1 mice exhibit increased PPARgamma2 and decreased IGF-1 transcript levels. These data suggest that high bone mass in L-SACC1 animals results, at least in part, from a negative regulatory effect of insulin on bone resorption and formation, which leads to decreased bone turnover. Because low bone turnover contributes to decreased bone quality and an increased incidence of fractures, studies on L-SACC1 mice may advance our understanding of altered bone homeostasis in type 2 diabetes.


Assuntos
Densidade Óssea/fisiologia , Antígeno Carcinoembrionário/metabolismo , Diferenciação Celular/fisiologia , Insulina/metabolismo , Fígado/metabolismo , Osteoclastos/metabolismo , Análise de Variância , Animais , Composição Corporal/fisiologia , Reabsorção Óssea/metabolismo , Antígeno Carcinoembrionário/genética , Moléculas de Adesão Celular/metabolismo , Citometria de Fluxo , Hiperinsulinismo/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Transgênicos , Obesidade/metabolismo , Osteogênese/fisiologia , Ligante RANK/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
J Orthop Res ; 22(5): 998-1003, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15304271

RESUMO

Mesenchymal stem cells (MSCs) have been used to repair connective tissue defects in several animal models. Compared to "natural healing" controls (no added cells), MSC-collagen gel constructs in rabbit tendon defects significantly improve repair biomechanics. However, ectopic bone forms in 28% of MSC-treated rabbit tendons. To understand the source of bone formation, three studies were performed. In the first study, the hypothesis was tested that MSCs delivered during surgery contribute to bone formation in the in vivo repair site. Adjacent histological sections in the MSC-treated repair tissue were examined for pre-labeled MSCs and for cells showing positive alkaline phosphatase (ALP) activity. Both cells were observed in serial sections in regions of ectopic bone. Contralateral "natural healing" tendons lacked both markers. In the other two studies, the effects of osteogenic supplements and construct geometry (monolayer vs. 3-D) on ALP activity were studied to test three hypotheses: that rabbit MSCs increase ALP activity over time in monolayer culture conditions; that adding osteogenic inducing supplements to the culture medium increases cellular protein in monolayer culture; and that rabbit MSCs increase ALP activity both in monolayer and in 3-D constructs, with and without media supplements. Culture in monolayer under similar conditions to in vivo (as in the first study) did not increase ALP at 2 or 4 weeks. Medium designed to increase osteogenic activity significantly increased cell numbers (cellular protein increased by 260%) but did not affect ALP activity either in monolayer or 3-D constructs (p>0.12). However, MSCs in 3-D constructs exhibited higher ALP activity than cells in monolayer, both in the presence (p<0.045) and absence of supplement (p<0.005). These results suggest that in vitro conditions may critically influence cell differentiation and protein expression. Mechanisms responsible for these effects are currently under investigation.


Assuntos
Fosfatase Alcalina/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Osteogênese , Tendões/cirurgia , Animais , Diferenciação Celular , Feminino , Células-Tronco Mesenquimais/enzimologia , Coelhos
8.
J Colloid Interface Sci ; 266(2): 346-58, 2003 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-14527458

RESUMO

29Si NMR, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) are used to monitor the synthesis of silica nanoparticles from the base-catalyzed hydrolysis of TEOS in methanol and ethanol. The reactions are conducted at a [TEOS] =0.5 M, low concentrations of ammonia ([NH(3)] =0.01-0.1 M), and [H(2)O] =1.1-4.4 M to resolve the initial size of the first nuclei and to follow their structural evolution. It is found that after an induction period where there is a buildup of singly hydrolyzed monomer, the first nuclei are fractal and open in structure. Interestingly, the nuclei are twice as large in ethanol (R(g) approximately 8 nm) as those in methanol (R(g) approximately 4 nm). The data suggest that the difference in primary particle size is possibly caused by a higher supersaturation ratio of the singly hydrolyzed monomer in methanol than in ethanol if it is assumed that the surface energy of the first nuclei is the same in methanol and ethanol. The particle number concentration and the volume fraction of the silica particles are calculated independently from the SAXS, DLS, and 29Si NMR results. Finally, the rate of nucleation is obtained from the particle number concentrations.

9.
Hernia ; 6(3): 120-3, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12209300

RESUMO

BACKGROUND: The use of prosthetic materials in tension-free incisional hernia repairs has diminished reherniation rates markedly; however, infection, intestinal fistulization, and seroma formation have been reported after repairs. Use of the Rives-Stoppa procedure for incisional hernia repair, in which the prosthesis is placed between the rectus abdominis muscle and the posterior sheath, may reduce occurrence of these problems. METHODS AND MATERIALS: Over a 6-year period 57 open abdominal wall incisional hernia repairs were performed using the Rives-Stoppa technique; 15 (26.3%) had previously undergone incisional hernia repair. The prosthetic materials used were polypropylene, expanded polytetrafluoroethylene (ePTFE), and ePTFE with perforations. The prosthesis size ranged from 8x8 cm to 20x28 cm (mean area 199.6 cm(2)). Follow-up consisted of an office visit 12 months postoperatively and at least one subsequent office visit or telephone interview; mean follow-up time was 34.9 months (range 11.7-81.9). RESULTS: There were no hernia recurrences (except in one patient whose prosthesis was removed), gastrointestinal complications, fistulas, or deaths. Seromas occurred postoperatively in seven patients (12.3%). Two patients (3.5%) had wound infections that required removal of the prosthesis. CONCLUSIONS: In this series the Rives-Stoppa technique had excellent long-term results, with minimal morbidity, in patients with large primary or recurrent incisional hernias. The absence of serious complications and hernia recurrences in patients with grafts in place suggests that the Rives-Stoppa procedure is the repair of choice in such patients.


Assuntos
Músculos Abdominais/cirurgia , Hérnia Ventral/cirurgia , Complicações Pós-Operatórias , Telas Cirúrgicas , Procedimentos Cirúrgicos Operatórios/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polipropilenos/uso terapêutico , Politetrafluoretileno/uso terapêutico , Recidiva , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Resultado do Tratamento
10.
J Clin Neurosci ; 8(4): 325-7, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11437571

RESUMO

Temozolomide has an evolving role in the treatment of high grade gliomas. Recent studies suggest that temozolomide is well tolerated and efficacious. This study retrospectively analysed the activity and toxicity associated with temozolomide at two Australian centres over a 24 month period. Fifty-six patients with recurrent high grade gliomas were treated with temozolomide. Patients received temozolomide orally at 150-200mg/m(2)daily, days 1-5, every 4 weeks. The median number of treatment cycles was 4 (1-12). Of the 56 patients, 15 (27%) achieved complete or partial response and 18 (32%) achieved minor response or stable disease. There were no episodes of febrile neutropenia and temozolomide was generally well tolerated. In conclusion, temozolomide is an active therapy in patients with recurrent high grade glioma and our results concord with published studies.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Glioma/tratamento farmacológico , Adulto , Idoso , Austrália , Neoplasias Encefálicas/mortalidade , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Feminino , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Temozolomida , Resultado do Tratamento
11.
Dis Colon Rectum ; 43(11): 1575-81, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11089596

RESUMO

PURPOSE: Inflammatory bowel disease surveillance strategies are designed to identify patients at greater than average risk for the development of invasive colonic carcinoma. Colonoscopic detection of mucosal dysplasia is considered the best available surveillance tool. However, the usefulness of dysplasia as a marker for cancer is uncertain. Furthermore, when dysplasia is found some suggest immediate colectomy, whereas others opt for continued surveillance. The aim of this study is to determine whether an association between dysplasia grade and cancer exists in patients with chronic ulcerative colitis, to ascertain the sensitivity, specificity, and positive predictive value of dysplasia as a cancer marker, and to clarify what action to take once dysplasia is discovered. METHODS: The pathology reports of 590 patients who underwent total proctocolectomy or restorative proctocolectomy for chronic ulcerative colitis were reviewed for dysplasia, grade of dysplasia, presence of carcinoma, and tumor stage. One hundred sixty of these patients had undergone colonoscopic examination within the year before surgery. Findings from these studies were also reviewed. RESULTS: Seventy-seven specimens (13.1 percent) contained at least one focus of dysplasia. Invasive cancers were found in 38 specimens (6.4 percent). Cancers were significantly more common among specimens with dysplastic changes (33/77 vs. 5/513; P < 0.001). Specimens with dysplasia of any grade were 36 times more likely to harbor invasive carcinoma. Stage III disease was found in association with indefinite or low-grade dysplasia in 5 of 26 (19.2 percent) of cases. Tumor stage did not correlate with dysplasia grade. Preoperative colonoscopy identified neoplastic changes in 57 (69.5 percent) cases. Dysplasia, cancer or both were missed in 25 cases. Lesions were correctly identified in only 31 (39.7 percent) of cases. Colonoscopically diagnosed dysplasia as a marker for synchronous cancer had a sensitivity of 81 percent and a specificity of 79 percent. The positive predictive value of a finding of preoperative dysplasia of any grade was 50 percent. The positive predictive value of a finding of low-grade dysplasia was 70 percent. CONCLUSIONS: Dysplasia is an unreliable marker for the detection of synchronous carcinoma. However, when dysplasia of any grade is discovered at colonoscopy, the probability of a coexistent carcinoma is relatively high. Colonoscopic evidence of low-grade dysplasia has a higher positive predictive value than either dysplasia associated mass or lesion or high-grade dysplasia. Dysplasia grade does not predict tumor stage. Because advanced cancer can be found in association with dysplastic changes of any grade, confirmed dysplasia of any grade is an indication for colectomy.


Assuntos
Colite Ulcerativa/complicações , Neoplasias do Colo/etiologia , Mucosa Intestinal/patologia , Lesões Pré-Cancerosas/etiologia , Proctocolectomia Restauradora , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colite Ulcerativa/patologia , Colite Ulcerativa/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Colonoscopia , Tomada de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Prognóstico , Índice de Gravidade de Doença
12.
Biotechnol Bioeng ; 70(5): 564-73, 2000 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-11042553

RESUMO

An enzymatic method to graft hexyloxyphenol onto the biopolymer chitosan was studied. The method employs tyrosinase to convert the phenol into a reactive o-quinone, which undergoes subsequent nonenzymatic reaction with chitosan. Reactions were conducted under heterogeneous conditions using chitosan films and also under homogeneous conditions using aqueous methanolic mixtures capable of dissolving both hexyloxyphenol and chitosan. Tyrosinase was shown to catalyze the oxidation of hexyloxyphenol in such aqueous methanolic solutions. Chemical evidence for covalent grafting onto chitosan was provided by three independent spectroscopic approaches. Specifically, enzymatic modification resulted in (1) the appearance of broad absorbance in the 350-nm region of the UV/vis spectra for chitosan films; (2) changes in the NH bending and stretching regions of chitosan's IR spectra; and (3) a base-soluble material with (1)H-NMR signals characteristic of both chitosan and the alkyl groups of hexyloxyphenol. Hexyloxyphenol modification resulted in dramatic changes in chitosan's functional properties. On the basis of contact angle measurements, heterogeneous modification of a chitosan film yielded a hydrophobic surface. Homogeneously modified chitosan offered rheological properties characteristic of associating water-soluble polymers.


Assuntos
Quitina/análogos & derivados , Monofenol Mono-Oxigenase/metabolismo , Éteres Fenílicos/química , Reologia/métodos , Quitina/química , Quitosana , Monofenol Mono-Oxigenase/química , Oxirredução , Fenóis/química , Fenóis/metabolismo , Propriedades de Superfície
13.
Nurs Case Manag ; 5(1): 13-25, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10855154

RESUMO

The results of a home-based preoperative bowel preparation, with and without the support of home care services, are compared with hospital-based preoperative bowel preparation. Length of stay, morbidity, and mortality rates; issues of patient satisfaction; and demographics are reported. The method and tools used in planning, implementing, and evaluating the home preoperative bowel preparation program are also shared. Other issues discussed are the healthcare market forces that promote an increased value of care. Economic and patient satisfaction considerations by employers, payers, and patients; the increasing influence of patient choice on healthcare provider selection and care setting preferences; the nursing workforce issues related to the impending shortage; and issues of regulatory and accrediting agencies are also discussed.


Assuntos
Administração de Caso/organização & administração , Serviços de Assistência Domiciliar/organização & administração , Enteropatias/cirurgia , Satisfação do Paciente , Cuidados Pré-Operatórios/enfermagem , Cuidados Pré-Operatórios/psicologia , Gestão da Qualidade Total/organização & administração , Adulto , Redução de Custos , Feminino , Humanos , Masculino , Marketing de Serviços de Saúde , Pessoa de Meia-Idade , Pesquisa em Avaliação de Enfermagem , Planejamento de Assistência ao Paciente , Educação de Pacientes como Assunto , Cuidados Pré-Operatórios/economia , Avaliação de Programas e Projetos de Saúde , Encaminhamento e Consulta
14.
Prostate ; 44(1): 19-25, 2000 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10861753

RESUMO

BACKGROUND: Exposure of male Wistar rats to estradiol-17beta (E(2)) in the presence or absence of dihydrotestosterone propionate (DHT) was previously shown to result in prostate inflammation. The present study examines, for the first time, changes in the expression level of several proinflammatory genes during the course of this experimentally induced prostatitis. METHODS: Adult male Wistar rats were given chronic exposure to E(2) + DHT by capsule implantation or were injected with E(2) for short-term exposure. Semiquantitative RT-PCR was employed to measure changes in proinflammatory transcript levels in the separated lobes of the prostate after various times of exposure to estrogen with or without DHT. RESULTS: We observed an upregulation of IL-1beta, IL-6, MIP-2, and inducible nitric oxide synthase (iNOS) after only 4 days treatment with E(2). After 4 weeks of treatment with E(2) + DHT, a significant increase in transcript levels of IL-4, IL-5, IL-6, MIP-2, eotaxin, and iNOS was detected, while IL-1beta and TNF-alpha transcript levels only increased slightly. No increase in transcript levels for cyclooxygenase-2 (cox-2), IFN-gamma, IL-2, or IL-12 was observed. CONCLUSIONS: Upregulation of proinflammatory transcripts occurred shortly after exposure to E(2) and well before any inflammatory cells were observed in the prostate. The pattern of gene expression resembled a T(H)2-type helper-cell response.


Assuntos
Quimiocinas CC , Citocinas/análise , Estradiol/toxicidade , Regulação da Expressão Gênica , Próstata/efeitos dos fármacos , Prostatite/genética , Animais , Quimiocina CCL11 , DNA/química , Primers do DNA/química , Di-Hidrotestosterona/administração & dosagem , Di-Hidrotestosterona/toxicidade , Modelos Animais de Doenças , Estradiol/administração & dosagem , Histocitoquímica , Processamento de Imagem Assistida por Computador , Interleucina-1/análise , Interleucina-4/análise , Interleucina-5/análise , Interleucina-6/análise , Masculino , Óxido Nítrico Sintase/análise , Próstata/patologia , Prostatite/induzido quimicamente , Prostatite/patologia , RNA/química , RNA/isolamento & purificação , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/análise
15.
J Biomed Mater Res ; 51(2): 233-40, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10825223

RESUMO

Mesenchymal stem cells (MSCs) were isolated from bone marrow, culture-expanded, and then seeded at 1, 4, and 8 million cells/mL onto collagen gel constructs designed to augment tendon repair in vivo. To investigate the effects of seeding density on the contraction kinetics and cellular morphology, the contraction of the cell/collagen constructs was monitored over time up to 72 h in culture conditions. Constructs seeded at 4 and 8 million cells/mL showed no significant differences in their gross appearance and dimensions throughout the contraction process. By contrast, constructs seeded at 1 million cells/mL initially contracted more slowly and their diameters at 72 h were 62 to 73% larger than those seeded at higher densities. During contraction, MSCs reoriented and elongated significantly with time. Implants prepared at higher seeding densities showed more well aligned and elongated cell nuclei after 72 h of contraction. Changes in nuclear morphology of the MSCs in response to physical constraints provided by the contracted collagen fibrils may trigger differentiation pathways toward the fibroblastic lineage and influence the cell synthetic activity. Controlling the contraction and organization of the cells and matrix will be critical for successfully creating tissue engineered grafts.


Assuntos
Células da Medula Óssea/citologia , Colágeno , Mesoderma/citologia , Traumatismos dos Tendões/terapia , Animais , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Células Cultivadas , Géis , Procedimentos Ortopédicos , Coelhos
16.
Mol Biochem Parasitol ; 111(2): 351-62, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11163442

RESUMO

Fragments of putative chitin synthase (chs) genes from two filarial species (Brugia malayi and Dirofilaria immitis) were amplified by PCR using degenerate primers. The full genomic and cDNA sequences were obtained for the B. malayi chs gene (Bm-chs-1); the predicted amino acid sequence is highly similar, over a large region, to two CHS sequences of the nematode Caenorhabditis elegans and also to two insect CHS sequences. Bm-chs-1 is abundantly transcribed in B. malayi adult females, independent of their fertilization status, but is also expressed in males and microfilariae. Oocytes and early embryos contain large amounts of Bm-chs-1 transcript by in situ hybridization, but later stage embryos within the maternal uterus show little or no Bm-chs-1 transcript. No specific hybridization could be demonstrated in maternal somatic tissues. Polyclonal antibodies were raised against a peptide expressed from a recombinant cDNA fragment of Bm-chs-1; immunostaining detected CHS protein in oocytes and early to midstage embryos. These studies characterize a gene that is likely to be essential to oogenesis and embryonic development in a parasitic nematode. Because chitin synthesis and eggshell formation begin after fertilization, the presence of CHS protein in early oocytes suggests that the enzyme must be activated as a result of fertilization. These studies also demonstrate that chitin synthesis may not be restricted to eggshell formation in nematodes, as the Bm-chs-1 gene is transcribed in life cycle stages other than adult females.


Assuntos
Brugia Malayi/embriologia , Brugia Malayi/enzimologia , Quitina Sintase/genética , Quitina Sintase/metabolismo , Sequência de Aminoácidos , Animais , Southern Blotting , Brugia Malayi/crescimento & desenvolvimento , Quitina Sintase/química , Dirofilaria immitis/embriologia , Dirofilaria immitis/enzimologia , Filariose Linfática/parasitologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genes de Helmintos , Gerbillinae , Imuno-Histoquímica , Hibridização In Situ , Masculino , Dados de Sequência Molecular , Óvulo/enzimologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
17.
Mt Sinai J Med ; 66(1): 20-5, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9989101

RESUMO

BACKGROUND: A prosthetic device must be used to repair ventral hernias in patients with insufficient tissue for a tension-free primary closure. Several prosthetic materials have been employed for this purpose, with varying results. We here review a long experience with the use of expanded polytetrafluoroethylene (ePTFE) patches in the open repair of large abdominal wall defects. METHODS: Demographic, operative, follow-up, and histologic data were recorded and analyzed for all patients in a surgical practice who were treated for large abdominal wall defects with open repair using ePTFE patches between November 1983 and March 1996. RESULTS: Ventral hernia repairs using an ePTFE patch were performed in 98 patients. In 48 (49%), the patient had already undergone at least one previous ventral hernia repair. Of the 98 operations, 78 were full-thickness repairs, 11 were Rives-Stoppa procedures, and 9 were onlay operations. Complications included 5 seromas, 3 fistulas related to removal of a previously implanted prosthesis, and 9 infections. In addition, 10 patients developed recurrent hernias not related to explantation of the patch because of infection or fistula. In 3 patients, infections were treated successfully without removal of the patch. There were no complications related to adhesions, erosion of the patch into the viscera, or bowel obstruction. Histologic studies of longterm ePTFE implants showed excellent fibrous tissue ingrowth and minimal foreign body response. CONCLUSIONS: Our long-term clinical experience indicates that prosthetic patches of ePTFE are safe and effective when used in the repair of large abdominal wall defects that cannot be closed primarily. Operative complications were within acceptable limits, as was the reherniation rate.


Assuntos
Hérnia Ventral/cirurgia , Politetrafluoretileno , Telas Cirúrgicas , Adulto , Idoso , Colágeno/ultraestrutura , Feminino , Hérnia Ventral/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Recidiva , Técnicas de Sutura , Resultado do Tratamento
18.
Dis Colon Rectum ; 40(5): 562-5, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9152184

RESUMO

PURPOSE: This study was undertaken to compare functional results, complications, preoperative durations of disease, and rates of dysplasia and neoplasia between older and younger chronic ulcerative colitis patients undergoing restorative proctocolectomy (RPC) with mucosectomy. METHODS: A total of 392 patients with a preoperative diagnosis of chronic ulcerative colitis underwent elective RPC with mucosection and handsewn ileoanal anastomosis. Pathologic reports were reviewed, with specific reference to findings of dysplasia or cancer. Functional results concerning the number of bowel movements per 24 hour period and the incidence of fecal soilage were obtained by direct or telephone patient interview. FINDINGS: Group I consisted of 326 patients aged 5 to 49 (mean, 30.9) years and 160 women. Group II comprised 66 patients aged 50 to 74 (mean, 56.9) years and 29 women. Duration of disease was significantly longer in the older group (6.2 vs. 15.6 years; P < 0.001). The older group had significantly higher rates of dysplasia (29/326 vs. 19/66; P < 0.0001) and malignancy (14/326 vs. 9/66; P = 0.003). Rates of complication, hospital days following RPC, and total hospital days for all causes were comparable between groups. Perfect day-time continence was observed in 81.6 percent of Group I and 80 percent of Group II patients (213/261 vs. 40/50; P = 0.79). Perfect continence during sleep was observed in 65.1 percent of Group I and 62 percent of Group II patients (170/261 vs. 31/50; P = 0.67). Mean number of bowel movements per 24 hour period for Group I was 6.3 +/- 0.2 and for Group II was 7.4 +/- 0.5. Mean difference, one movement per 24 hours, was not significant (95 percent confidence interval, -0.02 to 2.1; t = 1.95, P = 0.055). CONCLUSIONS: We conclude that patients older than 50 years are suitable candidates for RPC with mucosectomy. Functional results and complication rates are similar to those observed among younger patients. Patients older than 50 years have a significantly higher rate of concurrent dysplasia and malignant degeneration than younger patients, most probably because of a longer duration of disease. RPC with mucosal excision potentially lowers this risk by elimination of all colorectal mucosa.


Assuntos
Colite Ulcerativa/cirurgia , Proctocolectomia Restauradora , Fatores Etários , Doença Crônica , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Neoplasias do Colo/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
19.
J Clin Gastroenterol ; 23(1): 44-6, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8835899

RESUMO

This study was undertaken to determine preoperative criteria indicating which patients with Crohn's disease are most amenable to minimally invasive intestinal resection. Laparoscopic-assisted intestinal resection was attempted in 25 patients with Crohn's disease. Preoperative assessment of all patients included physical examination and contrast radiography. Laparoscopic intestinal resection was successfully completed in 19 patients. Four patients in whom both palpable mass and fistulous disease were present required conversion to open surgery. One patient found during surgery to have a fistula required conversion, as did one patient who had undergone previous ileocolic resection. In patients treated laparoscopically, oral alimentation, discontinuation of parenteral narcotics, and hospital discharge were possible at an average of 3.4, 4.2, and 6.5 days postsurgery, respectively. Patients operated upon using open techniques stayed in the hospital an average of 8.5 days. Laparoscopic-assisted intestinal resection is beneficial to selected patients with Crohn's disease. The presence of both a fixed mass and fistula on preoperative evaluation is predictive of conversion to open laparotomy and should be considered a relative contraindication. Patients with either a fixed mass or a fistula alone are more amenable to laparoscopic-assisted intestinal resection, while patients with primary uncomplicated Crohn's disease appear to be ideally suited to minimally invasive surgery.


Assuntos
Doença de Crohn/cirurgia , Laparoscopia , Doença de Crohn/diagnóstico , Humanos , Tempo de Internação , Seleção de Pacientes
20.
Mt Sinai J Med ; 63(2): 136-40, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8775146

RESUMO

In otherwise healthy individuals, disease caused by the fungus Histoplasma capsulatum manifests itself as a self-limiting pulmonary infection. Dissemination of the organisms may occur in a setting of compromised cellular immunity. Gastrointestinal involvement occurs in many such cases, but rarely it is clinically obvious and the disease seldom comes to the attention of the general surgeon. However, with the increasing incidence of acquired immunodeficiency syndromes, general surgeons are managing more of these patients than in the past. In our report, we describe a patient with acquired immunodeficiency syndrome who presented with gastrointestinal histoplasmosis.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Gastroenteropatias/complicações , Gastroenteropatias/microbiologia , Histoplasmose/complicações , Adulto , Feminino , Gastroenteropatias/diagnóstico , Histoplasmose/diagnóstico , Humanos
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