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1.
Ann Surg ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708612

RESUMO

OBJECTIVE: To assess informed consent documents from United States (US) institutions for verbiage regarding overlapping surgery. SUMMARY BACKGROUND DATA: Overlapping surgery remains a controversial practice. Recent guidance from the Senate Finance Committee and American College of Surgeons emphasizes transparency with patients regarding this practice through the informed consent process, but it remains unclear how many institutions adopted their recommendations. METHODS: Informed consent documents were collected from a national sample of 104 institutions and assessed for verbiage regarding overlapping surgery and/or attending absence during a surgical case. The verbiage of these forms was further analyzed for inclusion of key terms (e.g., "overlapping surgery," "critical portions") as well as transparency regarding surgeon absence. RESULTS: Thirty (29%) forms included verbiage regarding overlapping surgery and/or surgeon absence during a case. Most of these 30 utilized the terms "overlapping surgery" or "critical portions" (18 [60%] and 25 [83%], respectively), although only 3 (10%) explicitly stated that portions of the procedure that may be performed in the absence of the attending surgeon. Six forms (20%) specifically stated who may perform the procedure without the attending present, and 3 forms (10%) had patients acknowledge this section of the consent form with an additional signature or initial. Only 2 of the forms (7%) fulfilled all of the criteria set forth by the SFC. CONCLUSION: Detailed information regarding overlapping surgery is infrequently included in hospitals' procedure informed consent documents. Forms that include this information rarely provide explicit statements of attending presence and trainee participation, raising concerns regarding surgeon-patient transparency.

2.
Urology ; 188: 38-45, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38508532

RESUMO

OBJECTIVE: To prospectively capture patient-reported outcomes to assess the recovery profile of ureteroscopy (URS). MATERIALS AND METHODS: Adults undergoing URS for renal/ureteral stones were eligible for inclusion (11/2020-8/2022). Patients prospectively completed PROMIS - Pain Intensity, - Pain Interference, and - Ability to participate in social roles and activities in-person preoperatively (POD 0) and via email on POD 1, 7, 14, and 30. Scores are reported as T-scores (normalized to U.S. population, mean=50) with a change of 5 (0.5 SD) considered clinically significant. RESULTS: One hundred and seventy-eight participants enrolled at POD 0 (POD 1 =87, POD 7 =83, POD 14 =70, POD30 =67). There was a worsening of quality of life from day 0 to day 1 and day 0 to 7. All dimensions then improved with an increase in scores from day 0 to day 14 and day 0 to day 30. On multivariable analysis, the presence of a preoperative ureteral stent (OR 0.14) and use of semirigid URS (OR 0.33) were associated with a reduced odds for severe pain interference at day 1. The use of semirigid URS (OR 0.20) was associated with a reduced odds for severe worsening in the ability to participate in social roles at day 1. CONCLUSION: Ability to participate in social roles declines immediately postoperatively, while pain intensity and interference sharply increase. There is a gradual improvement until POD 30. Findings suggest preoperative stents may influence postoperative recovery. Results offer meaningful insight to assist in counseling and setting expectation for patients postoperatively.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Ureteroscopia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Dor Pós-Operatória/diagnóstico , Medição da Dor , Adulto , Participação Social , Idoso , Cálculos Renais/cirurgia , Cálculos Ureterais/cirurgia , Nefrolitíase/cirurgia , Recuperação de Função Fisiológica
3.
BMC Ophthalmol ; 24(1): 18, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200502

RESUMO

BACKGROUND: The authors sought to determine if resident operative time in cataract extraction and intraocular lens insertion (CE/IOL) affects early visual outcomes and post-operative recovery. They further sought to investigate if attending surgeons can reduce resident operative time. METHODS: This retrospective, chart-review, case series at single Veterans Affairs Hospital (VA Tennessee Valley Healthcare System) studied resident cataract surgeries between March 1, 2018 and March 31, 2020. Following power analysis, 420 eyes of 400 patients from all resident cataract surgeries were included. Eyes with attending as primary surgeon, laser-assisted cataract surgery, or concurrent secondary procedures were excluded. Linear mixed effect models were used to study the association between operative time and visual outcomes while adjusting for covariates including cumulative dissipated energy, preoperative factors, and intraoperative complications. RESULTS: Longer operative time was statistically associated with worse post-operative-day 1 (POD1) pinhole visual acuity (PH-VA) adjusting for cumulative dissipated energy and other operative factors (p = 0.049). Although resident physicians were the primary surgeons, the operative times were different between the ten supervising attending surgeons in the study (p < 0.001). CONCLUSION: The results suggest that increased resident operative time is a significant, independent risk factor for decreased POD1 PH-VA. Increased resident operative time is not associated with worsened long term visual outcomes. Attending surgeons may be able to reduce resident operative time, which is associated with improved early visual outcomes.


Assuntos
Extração de Catarata , Catarata , Cirurgiões , Humanos , Duração da Cirurgia , Estudos Retrospectivos
4.
J Nurse Pract ; 18(10): 1086-1090, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267334

RESUMO

The coronavirus disease 2019 pandemic presented challenges for urology patients to receive care in the format of a traditional clinic visit. For renal cancer patients, active surveillance and postintervention surveillance are the standard components of management. Telehealth, which was defined as a televideo encounter via the BlueJeans (Verizon) platform (a telehealth platform), was used to ensure continuity of care. Telehealth using the televideo modality was shown to be an effective model of care delivery to provide an optimal patient experience with ease of use.

5.
Urology ; 170: 60-65, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36058341

RESUMO

OBJECTIVE: To assess alterations in health-related quality of life (HRQOL) in patients with nephrolithiasis, given the limited prospective data on patient reported outcomes following surgical intervention with ureteroscopy. METHODS: Adults with either a renal or ureteral calculus who underwent ureteroscopy (URS) were recruited prospectively from 2017-2020. Participants completed the PROMIS-29 profile which measures the dimensions of physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance at enrollment, 1-, 6-, and 12-months. Scores are reported as T-scores (normalized to US-population) and were compared at each time point against the mean for the US-population (50) using one-sample Welch's t'test and between each pairwise time point comparison using a Wilcoxon signed rank test. RESULTS: At enrollment, a total of 69 participants completed the PROMIS-29 survey. As compared to the US-population mean, participants at enrollment had significantly different scores in physical function, fatigue, pain interference, depressive symptoms, anxiety, and sleep disturbance (all P<.05), but not ability to participate in social roles and activities. In pairwise comparisons, improvement was only observed from enrollment to 1-month in pain interference (P<.01) and fatigue (P = .03). However, there was improvement at a longer interval from enrollment to 12-months in all dimensions (pairwise comparisons, all P<.05) except depressive symptoms. CONCLUSION: The PROMIS-29 profile is responsive to changes in HRQOL for patients with nephrolithiasis undergoing URS, with improvement of PROMIS scores up to 12-months. This information can be utilized for patient counseling to guide expectations during the recovery period.


Assuntos
Cálculos Renais , Transtornos do Sono-Vigília , Adulto , Humanos , Qualidade de Vida , Estudos Prospectivos , Ureteroscopia/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Fadiga , Cálculos Renais/cirurgia , Dor
6.
J Foot Ankle Surg ; 61(3): 528-532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35012837

RESUMO

The relationship between managing patient expectations and postoperative functional outcomes has been studied widely in other areas of orthopedics, but there is a paucity of information in the foot and ankle literature. The primary objective of the study was to identify the most common patient "expectations" from hallux valgus surgery and establish over what time period postsurgery they would meet those goals. A prospective study of 45 consecutive patients was performed at a single center. This included adult patients (>18 years old) that underwent a scarf osteotomy for primary hallux valgus correction. Patients were followed up for 6 months and completed pre- and postoperative Manchester-Oxford Foot Questionnaire and Visual Analogue Scale scores. A separate "expectations" questionnaire was designed and completed assessing the patient's preoperative rehabilitation expectations compared to the actual time taken to achieve those goals. These included 5 domains: pain improvement, return to walking unaided, return to normal foot sensation, return to normal footwear, and return to driving. The postoperative functional scores demonstrated statistically significant improvement postsurgery (p < .001). It also highlighted the overall time frame over which the above expectations were met. On average, patients achieved satisfactory pain improvements 1.4 weeks earlier than expected (p < .001) along with trends toward an earlier return to driving function of patient expectation (p < .05). Patients can thus be reliably informed that their pain symptoms are likely to settle within one month of surgery. This should allow patients to prepare for their rehabilitation more informed, thus facilitating earlier weightbearing and return to function.


Assuntos
Hallux Valgus , Adolescente , Adulto , Humanos , Motivação , Osteotomia , Dor , Avaliação de Resultados da Assistência ao Paciente , Estudos Prospectivos , Resultado do Tratamento
7.
BMJ Case Rep ; 14(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637497

RESUMO

A woman in her 60s with a history of lower extremity vascular disease presented with extreme pain and wounds in her legs which had kept her from walking for several weeks. The patient's pain became intolerable throughout her hospital stay despite multiple surgical revascularisations. Biopsy of the patient's calf wounds revealed evidence of calciphylaxis, a diagnosis which corresponds with this patient's extreme pain. Our patient had no history of end-stage renal disease.


Assuntos
Calciofilaxia , Falência Renal Crônica , Biópsia , Calciofilaxia/etiologia , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Dor
8.
Urology ; 147: 81-86, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049231

RESUMO

OBJECTIVE: To better understand the degree and time to resolution of pain in the postoperative period, we captured patient-reported pain intensity and interference prospectively in patients following ureteroscopy for nephrolithiasis. MATERIALS AND METHODS: Adults undergoing ureteroscopy for renal/ureteral stones from 11/2018 to 1/2020 were eligible for inclusion. All received nonopioid postoperative pain control. Patients prospectively completed Patient-Reported Outcome Measurement Information System-Pain Intensity and Patient-Reported Outcome Measurement Information System-Pain Interference instruments preoperatively on postoperative day (POD) 0 and via email on POD 1, 7, and 14. Scores are reported as T-scores (normalized to US population, mean = 50) with changes of 5 (0.5 standard deviation) considered clinically significant. RESULTS: A total of 126 patients completed enrollment at POD 0 (POD 1 = 74, POD 7 = 61, POD 14 = 47). Compared to US means, intensity and interference were significantly different at all time point comparisons (Wilcoxon rank test; all P <.001) except intensity at POD 7 (P = .09) and interference at POD 14 (P = .12). For both, there was a significant difference at each time comparison (repeated measures ANOVA; all P <.05). Increasing age was predictive of lower intensity (Confidence Interval (CI): -0.31 to -0.04; P = .012) and interference (CI: -0.36 to -0.06; P =.01) at POD 1. The presence of a postoperative stent was predictive of higher intensity (CI: 0.68-10.81; P = .03) and interference (CI: 0.61-12.96; P = .03) at POD 7. Increasing age remained a predictor of lower interference at POD 1 on multivariable analysis (CI: -0.46 to -0.01; P = .03). CONCLUSION: Pain intensity and interference are elevated immediately, but intensity normalizes by POD 7, while interference remains elevated until POD 14. Age and indwelling ureteral stent influence both intensity and interference.


Assuntos
Cálculos Renais/cirurgia , Medição da Dor/estatística & dados numéricos , Dor Pós-Operatória/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Ureteroscopia/efeitos adversos , Adulto , Fatores Etários , Analgésicos não Narcóticos/uso terapêutico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Fatores de Risco , Stents/efeitos adversos , Fatores de Tempo , Ureteroscopia/instrumentação
9.
Neurourol Urodyn ; 39(8): 2433-2441, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32926460

RESUMO

AIM: Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches. METHODS: This is a multi-institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan-Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence. RESULTS: Two-hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% (n = 115/180) of women remained recurrence free at median follow-up of 14.6 months (IQR, 3-37). In unadjusted analysis, recurrence-free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence. CONCLUSION: This retrospective multi-institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.


Assuntos
Procedimentos de Cirurgia Plástica , Uretra/cirurgia , Estreitamento Uretral/cirurgia , Vagina/cirurgia , Adulto , Idoso , Dilatação , Endoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Retalhos Cirúrgicos/cirurgia , Resultado do Tratamento
11.
J Emerg Trauma Shock ; 12(2): 145-149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31198283

RESUMO

BACKGROUND: Rib fractures are common sequelae after blunt chest wall trauma. They can occur in isolation or association with life-threatening injuries to the head, thorax, and abdomen and may be complicated by hemothorax, pneumothorax, or lung contusions. Contiguous rib fractures can result in flail chest, which is associated with increased morbidity and mortality. This study aims to compare the risk factors, treatment modalities, and outcomes between patients with flail chest and nonflail chest postblunt trauma. PATIENTS AND METHODS: Data were retrospectively collected from all patients admitted with rib fractures from January 2016 to December 2016 to the Department of General Surgery, Khoo Teck Puat Hospital, Singapore. The outcomes identified were mortality, pain scores on injury day 1, 3, 5, and 7, injury severity score, duration of mechanical ventilation, worst partial pressure arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, length of intensive care unit (ICU) stay, and pulmonary complications. RESULTS: Motor vehicle accident was the most common cause of rib fractures (63.1%, n = 123). Patients with flail chest had more associated pneumothorax (53.8% vs. 35.2%) and lung contusions (53.8% vs. 30.2%) compared to those without flail chest and underwent more investigations such as inpatient-computed tomography scans (76.9% vs. 59.3%), interventions such as chest tube insertion (61.5% vs. 19.8%), and ICU admission (46.1 vs. 13.7%). Patients also had higher pain scores, used more analgesic modalities, and had increased inpatient mortality (30.8% vs. 4.4%). CONCLUSION: Flail chest is associated with higher morbidity and mortality. Proactive management from a multidisciplinary team such as identification of high-risk patients in particular patients with flail chest, early admission to critical care, and protocols including multimodal pain management, respiratory support, and rehabilitation should be instituted.

13.
Arch Pathol Lab Med ; 139(1): 106-21, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25549147

RESUMO

CONTEXT: During the last 5 to 10 years, significant progress has been made in the molecular characterization of soft tissue tumors, predominantly with the identification of recurrent translocations or amplification of certain genes in different tumor types. Alongside this, translational efforts have identified many novel and diagnostically useful immunohistochemical markers for many of these tumor types. OBJECTIVE: This article reviews a select group of recently described immunohistochemical markers of particular use in the evaluation of mesenchymal neoplasms; the underlying biology of the protein product, practical utility, and limitations of each marker are discussed in detail. DATA SOURCES: Literature review, authors' research data, and personal practice experience serve as sources. CONCLUSIONS: There are many diagnostically useful immunohistochemical markers to help confirm the diagnosis of many different soft tissue tumor types, some of which have reduced the need for additional, and more costly, studies, such as fluorescence in situ hybridization. However, no one marker is 100% specific for a given tumor, and knowledge of potential pitfalls and overlap in patterns of staining among other tumor types is crucial to ensure the appropriate application of these markers in clinical practice.


Assuntos
Biomarcadores Tumorais/análise , Imuno-Histoquímica/métodos , Neoplasias de Tecidos Moles/diagnóstico , Diagnóstico Diferencial , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/metabolismo
14.
Arch Dermatol ; 148(3): 363-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22431777

RESUMO

BACKGROUND: The development of keratoacanthomas (KAs) and well-differentiated squamous cell carcinomas (SCCs) is a known adverse effect of novel BRAF inhibitors such as vemurafenib. With multiple such neoplasms often arising after BRAF inhibitor therapy, surgical excision is often impractical. OBSERVATIONS: We describe a patient with stage IV melanoma who received the BRAF inhibitor vemurafenib (recently approved by the US Food and Drug Administration) as part of a clinical trial and developed numerous diffuse, pathology-proven KAs and SCCs. The high number of lesions across a broad area precluded surgical treatment; instead, a noninvasive field approach using photodynamic therapy (PDT) was initiated. Compared with untreated tumors, most lesions demonstrated significant clinical regression following successive cycles of PDT. CONCLUSIONS: Given vemurafenib's recent approval by the US Food and Drug Administration, we provide a timely case report on the effective use of PDT in the treatment of BRAF inhibitor-associated KAs and SCCs. Although further studies are needed to better understand the biological processes of these secondary neoplasms, our observation provides an alternative noninvasive solution for improving the quality of life for patients receiving BRAF inhibitor therapy.


Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/tratamento farmacológico , Indóis/efeitos adversos , Ceratoacantoma/induzido quimicamente , Ceratoacantoma/tratamento farmacológico , Melanoma/tratamento farmacológico , Fotoquimioterapia , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/efeitos adversos , Idoso , Ácido Aminolevulínico/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/tratamento farmacológico , Progressão da Doença , Humanos , Indóis/uso terapêutico , Masculino , Melanoma/patologia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/induzido quimicamente , Neoplasias Primárias Múltiplas/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Sulfonamidas/uso terapêutico , Vemurafenib
15.
Gynecol Oncol Case Rep ; 2(4): 124-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-24371642

RESUMO

► Skin metastasis of ovarian cancer is rare, often nodular in appearance, and conveys a poor prognosis. ► This patient developed an unusual maculo-papular rash which was biopsy-proven to be metastatic endometrioid adenocarcinoma. ► Pruritic symptoms from skin metastases should be palliated; SSRIs, local radiation, and topical creams all may play a role.

16.
J Carcinog ; 8: 14, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19822958

RESUMO

BACKGROUND: Recent epidemiologic evidence suggests that the common polymorphism at amino acid residue 399 of the x-ray cross complementing-1 (XRCC1) protein, a key component of the base excision repair (BER) pathway for DNA damage, plays a significant role in the genetic variability of individuals in terms of the mutagenic damage they experience following exposure to the carcinogen vinyl chloride (VC). The aim of this study was to provide support for the biological plausibility of these epidemiologic observations with experimental data derived from cell lines in culture from individuals who were either homozygous wild-type or homozygous variant for this XRCC1 polymorphism following exposure to chloroethylene oxide (CEO), the active metabolite of VC, with measurement of the induced etheno-DNA adducts before and after repair. MATERIALS AND METHODS: Immortalized lymphoblast cell lines from seven VC workers (four homozygous wild-type and three homozygous variant for the 399 XRCC1 polymorphism) were exposed to CEO, and etheno-adenosine (epsilonA) adduct levels were determined by enzyme-linked immunosorbent assay (ELISA) pre-exposure and at 0, 4, 8 and 24 h following exposure. RESULTS: The average epsilonA adduct levels were statistically significantly higher in the variant cells compared to the wild-type cells at 8 and 24 h following exposure (P Conclusion: These results are consistent with the epidemiologic findings of the types of VC-induced biomarkers observed in exposed individuals and the mutational spectra found in the resultant tumors as well as the key role that BER, especially XRCC1, plays in this carcinogenic pathway.

17.
DNA Repair (Amst) ; 8(2): 182-9, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19013261

RESUMO

Loop II of DNA polymerase beta (pol beta) consists of 14 amino acid residues and is highly flexible and solvent exposed. Previous research from our laboratory has shown that this loop is important for polymerase activity and fidelity. In the study presented here, we demonstrate that a shortened five amino acid residue loop compromises the fidelity of pol beta. This five-residue loop, termed ENEYP, induces one base frameshift errors and A-C transversions within a specific sequence context. We demonstrate that ENEYP misincorporates dGTP opposite template A at higher efficiencies than wild-type pol beta. The kinetic basis for misincorporation is a defect in discrimination of the correct from incorrect dNTP substrate at the level of ground-state binding. Our results are consistent with the idea that loop II of pol beta functions to maintain accurate DNA synthesis by a direct or indirect influence on the nucleotide binding pocket.


Assuntos
DNA Polimerase beta/química , DNA Polimerase beta/metabolismo , Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Pareamento Incorreto de Bases , Sequência de Bases , DNA/metabolismo , Mutação da Fase de Leitura , Guanosina Trifosfato/metabolismo , Herpesvirus Humano 1/enzimologia , Cinética , Dados de Sequência Molecular , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Ligação Proteica , Estrutura Secundária de Proteína , Ratos , Deleção de Sequência , Relação Estrutura-Atividade , Especificidade por Substrato , Timidina Quinase/metabolismo
18.
J Emerg Med ; 29(4): 417-20, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16243198

RESUMO

Public education to prevent carbon monoxide exposure during ice storms has been recommended; its effects remain unexamined. We compared patients seen for carbon monoxide inhalation at the area's only academic Emergency Department during 1991 and 2003 ice storms; educational efforts were more intense in 2003. There were fewer patients during the second storm (45 vs. 55); all recovered fully. The percentage of Caucasian patients rose (from 57% to 89%) whereas that of African-American patients fell (from 39% to 7%). Indoor grill use, associated with 11% of 1991 cases, was eliminated in 2003. Indoor gas generators remain the most common source. Carboxyhemoglobin levels correlate poorly with ambient carbon monoxide levels. Enhanced public education had a modest effect, especially in reducing the proportion of African-American patients and those from indoor grill use. Research on more effective public health education targeted at gas generator users and combined with physical interventions should be considered.


Assuntos
Intoxicação por Monóxido de Carbono/prevenção & controle , Fontes de Energia Elétrica/efeitos adversos , Combustíveis Fósseis/efeitos adversos , Educação em Saúde , Gelo , Exposição por Inalação/efeitos adversos , Saúde Pública , Tempo (Meteorologia) , Adolescente , Adulto , Intoxicação por Monóxido de Carbono/etnologia , Intoxicação por Monóxido de Carbono/etiologia , Criança , Feminino , Promoção da Saúde , Hospitais Pediátricos , Humanos , Masculino , Pessoa de Meia-Idade , New York , Estudos Retrospectivos , Marketing Social
19.
Clin Cancer Res ; 11(13): 4851-6, 2005 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-16000583

RESUMO

We have previously identified the retinoid X receptor-alpha (RXRalpha) as an insulin-like growth factor binding protein-3 (IGFBP-3) nuclear binding partner, which is required for IGFBP-3-induced apoptosis. In the current study, we investigated the biological interactions of the RXR ligand, VTP194204 and rhIGFBP-3, in vitro and in vivo. In vitro, IGFBP-3 and VTP194204 individually induced apoptosis, and suppressed cell growth in prostate cancer cell lines in an additive manner. In vivo, LAPC-4 xenograft-bearing severe combined immunodeficiency mice treated daily with saline, IGFBP-3, and/or VTP194204 for 3 weeks showed no effect of individual treatments with IGFBP-3 or VTP194204 on tumor growth. However, the combination of IGFBP-3 and VTP194204 treatments inhibited tumor growth by 50% and induced a significant reduction in serum prostate-specific antigen levels. In terminal nucleotidyl transferase-mediated nick end labeling immunohistochemistry of LAPC-4 xenografts, there was modest induction of apoptosis with either IGFBP-3 or VTP194204 individual treatment, but combination therapy resulted in massive cell death, indicating that IGFBP-3 and VTP194204 have a synergistic effect in preventing tumor growth by apoptosis induction. In summary, this is an initial description of the successful therapeutic use of IGFBP-3 as a cancer therapy in vivo, and shows that combination treatment of IGFBP-3 and RXR ligand has a synergistic effect on apoptosis induction leading to substantial inhibition of prostate cancer xenograft growth. Taken together, these observations suggest that combination therapy with IGFBP-3 and RXR ligands may have therapeutic potential for prostate cancer treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Retinoides/farmacologia , Animais , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/administração & dosagem , Ligantes , Masculino , Camundongos , Camundongos SCID , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Receptores X de Retinoides/metabolismo , Retinoides/administração & dosagem , Retinoides/metabolismo , Fatores de Tempo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Virol Methods ; 128(1-2): 135-42, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15941597

RESUMO

Many viruses enter cells via an interaction of the viral envelope glycoprotein (Env) with receptor inducing fusion of viral and cellular membranes. These interactions are often evaluated in cell-cell fusion, gene-reporting systems with effector cells expressing Env and target cells expressing receptors. A common system utilizes vaccinia virus encoding T7 RNA polymerase (RNAP) in effector cells and a T7 promoted reporter plasmid in target cells. Fusion is quantified with expression of the reporter plasmid. However, direct activation of reporter plasmid from vaccinia virus can occur increasing background activity. We report here a modification of this assay in which T7 RNAP is expressed from a plasmid rather than vaccinia. This modification increased sensitivity with a ten-fold reduction in background. A novel dual T7/SP6 RNAP fusion assay was also developed to allow rapid screening for functional Env clones. Using these assays, we show that Envs from two CD4-independent HIV-2 isolates (VCP and ROD/B), which are able to fuse with chemokine receptor CXCR4 in a CD4-independent manner, are also able to fuse with alternative coreceptors GPR1 and GPR15 in the absence of CD4. The assay could also detect fusion of murine leukemia virus on target cells expressing the ecotropic MCAT-1 receptor showing its broad utility in other viral systems.


Assuntos
Fusão Celular/métodos , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Produtos do Gene env/metabolismo , HIV-2/patogenicidade , Plasmídeos , Proteínas Virais/genética , Proteínas Virais/metabolismo , Animais , Antígenos CD4/metabolismo , Linhagem Celular , Produtos do Gene env/genética , HIV-2/genética , HIV-2/metabolismo , Humanos , Vírus da Leucemia Murina/metabolismo , Vírus da Leucemia Murina/patogenicidade , Camundongos , Plasmídeos/genética , Receptores CXCR4/metabolismo , Receptores de HIV/metabolismo
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