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1.
J Neurooncol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896356

RESUMEN

PURPOSE: A systematic review was conducted to investigate differences in incidence and primary origin of synchronous brain metastasis (sBM) in varying racial groups with different primary cancers. METHODS: Adhering to PRISMA 2020 guidelines a search was conducted using PubMed and Ovid databases for publications from January 2000 to January 2023, with search terms including combinations of "brain metastasis," "race," "ethnicity," and "incidence." Three independent reviewers screened for inclusion criteria encompassing studies clearly reporting primary cancer sites, patient demographics including race, and synchronous BM (sBM) incidence. RESULTS: Of 806 articles, 10 studies comprised of mainly adult patients from the United States met final inclusion for data analysis. Higher sBM incidence proportions were observed in American Indian/Alaska native patients for primary breast (p < 0.001), colorectal (p = 0.015), and esophageal cancers (p = 0.024) as well as in Asian or Pacific islanders for primary stomach (p < 0.001), thyroid (p = 0.006), and lung/bronchus cancers (p < 0.001) yet higher proportions in White patients for malignant melanoma (p < 0.001). Compared to White patients, Black patients had higher sBM incidence likelihood in breast cancer (OR = 1.27, p = 0.01) but lower likelihood in renal (OR = 0.46, p < 0.001) and esophageal cancers (OR = 0.31, p = 0.005). American Indian/Alaska native patients had a higher sBM likelihood (OR = 3.78, p = 0.004) relative to White patients in esophageal cancer. CONCLUSIONS: These findings reveal several comparative racial differences in sBM incidence arising from different primary cancer origins, underscoring a need for further research to explain these variations. Identifying the factors contributing to these disparities holds the potential to promote greater equity in oncological care according to cancer type.

2.
Orthopedics ; 47(2): e85-e89, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37757748

RESUMEN

Advances in artificial intelligence and machine learning models, like Chat Generative Pre-trained Transformer (ChatGPT), have occurred at a remarkably fast rate. OpenAI released its newest model of ChatGPT, GPT-4, in March 2023. It offers a wide range of medical applications. The model has demonstrated notable proficiency on many medical board examinations. This study sought to assess GPT-4's performance on the Orthopaedic In-Training Examination (OITE) used to prepare residents for the American Board of Orthopaedic Surgery (ABOS) Part I Examination. The data gathered from GPT-4's performance were additionally compared with the data of the previous iteration of ChatGPT, GPT-3.5, which was released 4 months before GPT-4. GPT-4 correctly answered 251 of the 396 attempted questions (63.4%), whereas GPT-3.5 correctly answered 46.3% of 410 attempted questions. GPT-4 was significantly more accurate than GPT-3.5 on orthopedic board-style questions (P<.00001). GPT-4's performance is most comparable to that of an average third-year orthopedic surgery resident, while GPT-3.5 performed below an average orthopedic intern. GPT-4's overall accuracy was just below the approximate threshold that indicates a likely pass on the ABOS Part I Examination. Our results demonstrate significant improvements in OpenAI's newest model, GPT-4. Future studies should assess potential clinical applications as AI models continue to be trained on larger data sets and offer more capabilities. [Orthopedics. 2024;47(2):e85-e89.].


Asunto(s)
Internado y Residencia , Procedimientos Ortopédicos , Ortopedia , Humanos , Ortopedia/educación , Inteligencia Artificial , Evaluación Educacional , Competencia Clínica
3.
World Neurosurg ; 179: e160-e165, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37597659

RESUMEN

BACKGROUND: Artificial intelligence (AI) and machine learning have transformed health care with applications in various specialized fields. Neurosurgery can benefit from artificial intelligence in surgical planning, predicting patient outcomes, and analyzing neuroimaging data. GPT-4, an updated language model with additional training parameters, has exhibited exceptional performance on standardized exams. This study examines GPT-4's competence on neurosurgical board-style questions, comparing its performance with medical students and residents, to explore its potential in medical education and clinical decision-making. METHODS: GPT-4's performance was examined on 643 Congress of Neurological Surgeons Self-Assessment Neurosurgery Exam (SANS) board-style questions from various neurosurgery subspecialties. Of these, 477 were text-based and 166 contained images. GPT-4 refused to answer 52 questions that contained no text. The remaining 591 questions were inputted into GPT-4, and its performance was evaluated based on first-time responses. Raw scores were analyzed across subspecialties and question types, and then compared to previous findings on Chat Generative pre-trained transformer performance against SANS users, medical students, and neurosurgery residents. RESULTS: GPT-4 attempted 91.9% of Congress of Neurological Surgeons SANS questions and achieved 76.6% accuracy. The model's accuracy increased to 79.0% for text-only questions. GPT-4 outperformed Chat Generative pre-trained transformer (P < 0.001) and scored highest in pain/peripheral nerve (84%) and lowest in spine (73%) categories. It exceeded the performance of medical students (26.3%), neurosurgery residents (61.5%), and the national average of SANS users (69.3%) across all categories. CONCLUSIONS: GPT-4 significantly outperformed medical students, neurosurgery residents, and the national average of SANS users. The mode's accuracy suggests potential applications in educational settings and clinical decision-making, enhancing provider efficiency, and improving patient care.


Asunto(s)
Neuralgia , Neurocirugia , Estudiantes de Medicina , Humanos , Inteligencia Artificial , Procedimientos Neuroquirúrgicos
4.
Front Neurol ; 14: 1141059, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37333002

RESUMEN

Background and purpose: Telestroke has grown significantly since its implementation. Despite growing utilization, there is a paucity of data regarding the diagnostic accuracy of telestroke to distinguish between stroke and its mimics. We aimed to evaluate diagnostic accuracy of telestroke consultations and explore the characteristics of misdiagnosed patients with a focus on stroke mimics. Methods: We conducted a retrospective study of all the consultations in our Ochsner Health's TeleStroke program seen between April 2015 and April 2016. Consultations were classified into one of three diagnostic categories: stroke/transient ischemic attack, mimic, and uncertain. Initial telestroke diagnosis was compared with the final diagnosis post review of all emergency department and hospital data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for diagnosis of stroke/TIA versus mimic were calculated. Area under receiver-operating characteristic curve (AUC) analysis to predict true stroke was performed. Bivariate analysis based on the diagnostic categories examined association with sex, age, NIHSS, stroke risk factors, tPA given, bleeding after tPA, symptom onset to last known normal, symptom onset to consult, timing in the day, and consult duration. Logistic regression was performed as indicated by bivariate analysis. Results: Eight hundred and seventy-four telestroke evaluations were included in our analysis. Accurate diagnosis through teleneurological consultation was seen in 85% of which 532 were strokes (true positives) and 170 were mimics (true negatives). Sensitivity, specificity, PPV, NPV were 97.8, 82.5, 93.7 and 93.4%, respectively. LR+ and LR- were 5.6 and 0.03. AUC (95% CI) was 0.9016 (0.8749-0.9283). Stroke mimics were more common with younger age and female gender and in those with less vascular risk factors. LR revealed OR (95% CI) of misdiagnosis for female gender of 1.9 (1.3-2.9). Lower age and lower NIHSS score were other predictors of misdiagnosis. Conclusion: We report high diagnostic accuracy of the Ochsner Telestroke Program in discriminating stroke/TIA and stroke mimics, with slight tendency towards over diagnosis of stroke. Female gender, younger age and lower NIHSS score were associated with misdiagnosis.

5.
Cureus ; 14(1): e21023, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35154993

RESUMEN

Background and objective The optimal timing of anterior crucial ligament reconstruction (ACLR) remains a matter of controversy. A revision procedure is performed to improve knee function, correct instability, and enable a safe return to daily function when primary ACLR fails. The present study aimed to determine if the timing of primary ACLR is predictive of revision surgery. Methods All patients who underwent primary ACLR at the West Virginia University from January 2008 to December 2018 were identified. Patients were initially grouped into early (≤30 days) and late (>30 days) ACLR based on the onset of the initial injury. The major outcome measure of this study was the incidence of revision ACLR following primary ACLR. Results A total of 233 primary ACLRs were included. The incidence of ACLR revisions was 9.4%. The timing of primary ACLR, when categorized into early and late ACLRs, was not found to influence revision risk (p=0.384). Additionally, the damaged anatomical structures based on the postoperative diagnosis at the time of ACLR did not influence the odds of revision ACLR (p=0.9721). Conclusion Our study found that the timing of primary ACLR did not influence the revision rates when categorizing primary surgery time into early and late subgroups.

6.
Cureus ; 13(11): e19505, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34912642

RESUMEN

OBJECTIVE:  Exertional heat stroke (EHS) is a significant cause of morbidity and mortality in athletes and active individuals. In the field, initial management of exertional heat illness is based on rapid whole-body cooling. Cold-water immersion (CWI) is considered the superior cooling modality for EHS treatment. However, there often is a disconnect between the sports medicine community and the emergency medical service (EMS) community. Well-written emergency action plans may fail if EMS protocols do not allow for CWI in initial management. This is the first study to look at the current national EMS protocols regarding prehospital management of EHS. The purpose of our study was to assess the status of heat illness protocols regarding CWI for EHS in all 50 states plus Washington, DC.  Methods: An internet search was performed to find EHS protocols. Statewide protocols were preferred. Several parameters were recorded for each protocol including whether: 1) CWI was the recommended cooling treatment for EHS and 2) CWI was explicitly permitted to be completed prior to transportation. RESULTS:  We found nine of the 51 protocols, or 17.6%, explicitly recommended CWI and 11 of the 51, or 21.6%, specifically instructed EMS personnel to complete CWI or cooling methods prior to transport. However, six protocols, or 11.8%, provided the recommendation instructing some variation of the phrase "do not delay transport to cool the patient." CONCLUSION:  Despite the medical literature endorsing CWI as the most effective treatment modality in a prehospital setting for exertional heat illness, EMS protocols largely fail to reflect this which leads to mismanagement and inadequate care of EHS patients. While CWI is not always available, all EMS protocols should include a systematic practical guideline for a heat illness patient when employing cooling treatment with an emphasis on CWI when available as the preferred treatment technique for EHS and the concept of "cool first, transport second."

7.
Cytoskeleton (Hoboken) ; 75(5): 201-212, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29466836

RESUMEN

Epithelial-mesenchymal transition (EMT) is an important process that mediates organ development and wound healing, and in pathological contexts, it can contribute to the progression of fibrosis and cancer. During EMT, cells exhibit marked changes in cytoskeletal organization and increased expression of a variety of actin associated proteins. Here, we sought to determine the role of caldesmon in mediating EMT in response to transforming growth factor (TGF)-ß1. We find that the expression level and phosphorylation state of caldesmon increase as a function of time following induction of EMT by TGFß1 and these changes in caldesmon correlate with increased focal adhesion number and size and increased cell contractility. Knockdown and forced expression of caldesmon in epithelial cells reveals that caldesmon expression plays an important role in regulating the expression of the myofibroblast marker alpha smooth muscle actin. Results from these studies provide insight into the role of cytoskeletal associated proteins in the regulation of EMT and may suggest ways to target the cell cytoskeleton for regulating EMT processes.


Asunto(s)
Proteínas de Unión a Calmodulina/biosíntesis , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Miofibroblastos/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Animales , Citoesqueleto/metabolismo , Células Epiteliales/citología , Femenino , Ratones , Miofibroblastos/citología
8.
Prostate Cancer Prostatic Dis ; 18(2): 87-95, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25622539

RESUMEN

It is now recognized that the tumor microenvironment creates a protective neo-tissue that isolates the tumor from the various defense strategies of the body. Evidence demonstrates that, with successive therapeutic attempts, cancer cells acquire resistance to individual treatment modalities. For example, exposure to cytotoxic drugs results in the survival of approximately 20-30% of the cancer cells as only dividing cells succumb to each toxic exposure. With follow-up treatments, each additional dose results in tumor-associated fibroblasts secreting surface-protective proteins, which enhance cancer cell resistance. Similar outcomes are reported following radiotherapy. These defensive strategies are indicative of evolved capabilities of cancer to assure successful tumor growth through well-established anti-tumor-protective adaptations. As such, successful cancer management requires the activation of multiple cellular 'kill switches' to prevent initiation of diverse protective adaptations. Thermal therapies are unique treatment modalities typically applied as monotherapies (without repetition) thereby denying cancer cells the opportunity to express defensive mutations. Further, the destructive mechanisms of action involved with cryoablation (CA) include both physical and molecular insults resulting in the disruption of multiple defensive strategies that are not cell cycle dependent and adds a damaging structural (physical) element. This review discusses the application and clinical outcomes of CA with an emphasis on the mechanisms of cell death induced by structural, metabolic, vascular and immune processes. The induction of diverse cell death cascades, resulting in the activation of apoptosis and necrosis, allows CA to be characterized as a combinatorial treatment modality. Our understanding of these mechanisms now supports adjunctive therapies that can augment cell death pathways.


Asunto(s)
Apoptosis/genética , Criocirugía/métodos , Neoplasias de la Próstata/cirugía , Microambiente Tumoral/genética , Antineoplásicos/uso terapéutico , Terapia Combinada , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Transducción de Señal , Microambiente Tumoral/efectos de los fármacos
9.
Cryobiology ; 68(1): 1-11, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24239684

RESUMEN

While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer, which while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer.


Asunto(s)
Criocirugía/métodos , Próstata/cirugía , Neoplasias de la Próstata/cirugía , Apoptosis , Terapia Combinada , Humanos , Masculino , Células Madre Neoplásicas/patología , Neovascularización Patológica , Próstata/irrigación sanguínea , Próstata/patología , Neoplasias de la Próstata/irrigación sanguínea , Neoplasias de la Próstata/patología , Microambiente Tumoral
10.
Prostate Cancer Prostatic Dis ; 16(1): 41-9, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23229563

RESUMEN

BACKGROUND: Critical to the continual improvement of cryoablation efficacy is deciphering the biochemical responses of cells to low-temperature exposure. The identification of delayed-onset cell death has allowed for the manipulation of cellular responses through the regulation of apoptosis. We hypothesized that in addition to delayed apoptotic events associated with mild subfreezing temperatures (10 to -25 °C), cells exposed to ultra-low temperatures (<-30 °C) may undergo rapid, early-onset apoptosis. METHODS: Human prostate cancer model and cells (PC-3) were exposed to temperatures of -60, -30 and -15 °C to simulate a cryoablative procedure. Using a combination of flow-cytometry, fluorescent microscopy and western blot analyses, samples were assessed at various times post thaw to identify the presence, levels and the pathways involved in cell death. RESULTS: Exposure to temperatures <-30 °C yielded a significant apoptotic population within 30 min of thawing, peaking at 90 min (~40%), and by 6 h, only necrosis was observed. In samples only reaching temperatures >-30 °C, apoptosis was not noted until 6-24 h post thaw, with the levels of apoptosis reaching ~10% (-15 °C) and ~25% (-30 °C) at 6 h post thaw. Further, it was found that early-onset apoptosis progressed through a membrane-mediated mechanism, whereas delayed apoptosis progressed through a mitochondrial path. CONCLUSIONS: These data demonstrate the impact of apoptotic continuum, whereby the more severe cryogenic stress activated the extrinsic, membrane-regulated pathway, whereas less severe freezing activated the intrinsic, mitochondrial-mediated path. The rapid induction and progression of apoptosis at ultra-low temperatures provides an explanation as to why such results have not previously been identified following freezing. Ultimately, an understanding of the events and signaling pathways involved in triggering apoptosis following freezing may provide a path for selective induction of the rapid-onset and delayed programmed cell death pathways in an effort to improve the overall cryoablation efficacy.


Asunto(s)
Apoptosis/fisiología , Frío , Criocirugía , Neoplasias de la Próstata/metabolismo , Western Blotting , Línea Celular Tumoral , Citometría de Flujo , Humanos , Masculino , Microscopía Fluorescente
11.
Prostate Cancer Prostatic Dis ; 14(2): 97-104, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21221127

RESUMEN

Cryotherapy has emerged as a primary treatment option for prostate cancer (CaP); however, incomplete ablation in the periphery of the cryogenic lesion can lead to recurrence. Accordingly, we investigated the use of a non-toxic adjunctive agent, vitamin D3 (VD3), with cryotherapy to sensitize CaP to low temperature-induced, non-ice rupture-related cell death. VD3 (calcitriol) has been identified as a possible adjunct in the treatment of cancer because of its antiproliferative and antitumorigenic properties. This study aimed to identify the cellular responses and molecular pathways activated when VD3 (calcitriol) is combined with cryotherapy in a murine CaP model. Single freeze-thaw events above -15 °C had little effect on cancer cell viability; however, pretreatment with calcitriol in conjunction with cryo significantly increased cell death. The -15 °C calcitriol combination increased cell death to 55% following a single freeze compared with negligible cell loss by freezing or calcitriol alone. Repeated cryo combination yielded 90% cell death compared with 65% in dual freeze-only cycles. Western blot analysis following calcitriol cryosensitization regimes confirmed the activation of apoptosis. Specifically, proapoptotic Bid and procaspase-3 were found to decrease at 1 h following combination treatment, indicating cleavage to the active forms. A parallel in vivo study confirmed the increased cell death when combining cryotherapy with calcitriol pretreatment. The development of an adjunctive therapy combining calcitriol and cryotherapy represents a potentially highly effective, less toxic, minimally invasive treatment option. These results suggest a role for calcitriol and cryo as a combinatorial treatment for CaP, with the potential for clinical translation.


Asunto(s)
Antineoplásicos/uso terapéutico , Calcitriol/uso terapéutico , Crioterapia/métodos , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Muerte Celular/efectos de los fármacos , Quimioterapia Adyuvante/métodos , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Células Tumorales Cultivadas
12.
Prostate Cancer Prostatic Dis ; 13(2): 151-61, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20066006

RESUMEN

Cryoablation has emerged as a primary therapy to treat prostate cancer. Although effective, the assumption that freezing serves as a ubiquitous lethal stress is challenged by clinical experience and experimental evidence demonstrating time-temperature-related cell-death dependence. The age-related transformation from an androgen-sensitive (AS) to an androgen-insensitive (AI) phenotype is a major challenge in the management of prostate cancer. AI cells exhibit morphological changes and treatment resistance to many therapies. As this resistance has been linked with alpha6beta4 integrin overexpression as a result of androgen receptor (AR) loss, we investigated whether alpha6beta4 integrin expression, as a result AR loss, contributes to the reported increased freeze tolerance of AI prostate cancer. A series of studies using AS (LNCaP LP and PC-3 AR) and AI (LNCaP HP and PC-3) cell lines were designed to investigate the cellular mechanisms contributing to variations in freezing response. Investigation into alpha6beta4 integrin expression revealed that AI cell lines overexpressed this protein, thereby altering morphological characteristics and increasing adhesion characteristics. Molecular investigations revealed a significant decrease in caspases-8, -9, and -3 levels in AI cells after freezing. Inhibition of alpha6beta4 integrin resulted in increased caspase activity after freezing (similar to AS cells) and enhanced cell death. These data show that AI cells show an increase in post-freeze susceptibility after inhibition of alpha6beta4 integrin function. Further understanding the role of androgen receptor-related alpha6beta4 integrin expression in prostate cancer cells responses to freezing might lead to novel options for neo-adjunctive treatments targeting the AR signaling pathway.


Asunto(s)
Andrógenos/uso terapéutico , Criocirugía , Resistencia a Antineoplásicos/genética , Integrina alfa6beta4/fisiología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/genética , Apoptosis , Adhesión Celular , Línea Celular Tumoral , Supervivencia Celular , Congelación , Humanos , Integrina alfa6beta4/genética , Integrina alfa6beta4/inmunología , Masculino , Necrosis , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
13.
Cryobiology ; 59(3): 229-43, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19833119

RESUMEN

Cryosurgery is the use of freezing temperatures to elicit an ablative response in a targeted tissue. This review provides a global overview of experimentation in vivo which has been the basis of advancement of this widely applied therapeutic option. The cellular and tissue-related events that underlie the mechanisms of destruction, including direct cell injury (cryolysis), vascular stasis, apoptosis and necrosis, are described and are related to the optimal methods of technique of freezing to achieve efficacious therapy. In vivo experiments with major organs, including wound healing, the putative immunological response following thawing, and the use of cryoadjunctive strategies to enhance cancer cell sensitivity to freezing, are described.


Asunto(s)
Neoplasias/cirugía , Animales , Vasos Sanguíneos/fisiopatología , Huesos/fisiopatología , Encéfalo/fisiopatología , Mama/fisiopatología , Quimioterapia Adyuvante , Criocirugía/instrumentación , Criocirugía/métodos , Esófago/fisiopatología , Ojo/fisiopatología , Femenino , Congelación , Corazón/fisiopatología , Humanos , Riñón/fisiopatología , Hígado/fisiopatología , Masculino , Necrosis , Tejido Nervioso/fisiopatología , Páncreas/fisiopatología , Próstata/fisiopatología , Sistema Respiratorio/fisiopatología , Piel/fisiopatología , Vejiga Urinaria/fisiopatología , Útero/fisiopatología , Cicatrización de Heridas/fisiología
14.
Technol Cancer Res Treat ; 6(2): 97-109, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17375972

RESUMEN

The techniques of present-day cryosurgery performed with multiprobe freezing apparatus and advanced imaging techniques yield predictable and encouraging results in the treatment of prostatic and renal cancers. Nevertheless, and not unique to cryosurgical treatment, the rates of persistent disease demonstrate the need for improvement in technique and emphasize the need for proper management of the therapeutic margin. The causes of persistent disease often relate to a range of factors including selection of patients, understanding of the extent of the tumor, limitations of the imaging techniques, and failure to freeze the tumor periphery in an efficacious manner. Of these diverse factors, the one most readily managed, but subject to therapeutic error, is the technique of freezing the tumor and appropriate margin to a lethal temperature [Baust, J. G., Gage, A. A. The Molecular Basis of Cryosurgery. BJU Int 95, 1187-1191 (2005)]. This article describes the recent experiments that examine the molecular basis of cryosurgery, clarifies the actions of the components of the freeze-thaw cycle, and defines the resultant effect on the cryogenic lesion from a clinical perspective. Further, this review addresses the important issue of management of the margin of the tumor through adjunctive therapy. Accordingly, a goal of this review is to identify the technical and future adjunctive therapeutic practices that should improve the efficacy of cryoablative techniques for the treatment of malignant lesions.


Asunto(s)
Criocirugía/métodos , Enfermedades de la Próstata/patología , Enfermedades de la Próstata/cirugía , Animales , Línea Celular Tumoral , Supervivencia Celular , Humanos , Masculino , Enfermedades de la Próstata/terapia , Temperatura
15.
Prostate Cancer Prostatic Dis ; 10(2): 175-84, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17297503

RESUMEN

Adjuvant therapies contribute to the successful treatment of cancer. Our previous reports have shown that combining cryoablation with cytotoxic agents enhances cell death. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic agent that preferentially induces apoptosis in a variety of human cancer cells. Human prostate cancer cells (PC-3) are resistant to many cytodestructive agents, including cryoablation and TRAIL. Here, we evaluated the effects of TRAIL combined with cryoablation on PC-3 and normal prostate (RWPE-1) cell death. Exposure of PC-3 cells to freezing (-10 degrees C) or TRAIL (500 ng/ml) results in minimal cell death, whereas a complete loss of viability is observed with the simultaneous combination. The synergistic effect was found to be due to a marked increase in apoptosis. Western blot analysis revealed a significant level of caspase-8 and -3 cleavage between 12 and 24 h post-exposure. Caspase activation assays provided similar results and also indicated a role for caspase-9. Inhibitors to caspase-8 and -9 along with a pan-caspase inhibitor were incorporated to determine which pathway was necessary for the combined efficacy. Inhibition of caspase-8 significantly blocked the combination-induced cell death compared to cells that did not receive the inhibitor (63% compared to 10% viable). The addition of the caspase-9 inhibitor resulted in only a minimal protection. Importantly, the combination was not effective when applied to normal prostate cells. The results describe a novel therapeutic model for the treatment of prostate cancer and provide support for future in vivo studies.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Próstata/terapia , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Inhibidores de Caspasas , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Criocirugía , Resistencia a Antineoplásicos , Humanos , Masculino , Neoplasias de la Próstata/cirugía
16.
Int J Gynaecol Obstet ; 92(1): 92-6, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16269146

RESUMEN

OBJECTIVE: To investigate socioeconomic correlates of and gender differences in attitudinal support for the discontinuation of FGC in Guinea. METHOD: Data from structured interviews of men aged 15-59 and women aged 15-49 years in the 1999 Demographic and Health Survey and multiple logistic regression methods were used to examine the relationship of socioeconomic factors and gender to attitudinal support for the discontinuation of FGC. RESULT: More than 9 out of 10 women had undergone FGC. Attitudinal support for FGC discontinuation was more prevalent among men than women. The odds of supporting the discontinuation of FGC were negatively related to beliefs in social approval of and religious support for FGC and its enhancement of women's marriageability, the number of perceived advantages of FGC, and women's low socioeconomic status. CONCLUSION: Community education, improvements in women's socioeconomic status and traditional and religious leader involvement would be critical for FGC eradication.


Asunto(s)
Actitud Frente a la Salud , Circuncisión Femenina/psicología , Conducta Social , Salud de la Mujer , Adolescente , Adulto , Circuncisión Femenina/efectos adversos , Escolaridad , Femenino , Guinea , Encuestas Epidemiológicas , Humanos , Entrevistas como Asunto , Modelos Logísticos , Masculino , Estado Civil , Persona de Mediana Edad , Factores Sexuales , Factores Socioeconómicos
17.
AIDS Care ; 17(2): 153-65, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15763711

RESUMEN

This study examined rates and predictors of self-reported HIV testing and willingness to test among married men aged 15-59 in Uganda. The data are nationally representative and drawn from the 2000-01 Uganda Demographic and Health Survey. The results of multiple regression analyses indicate that knowledge about AIDS, a history of paying for sex, spousal communication about HIV prevention, secondary or higher education, household wealth, and neighbourhood knowledge of a test site are associated with an increased likelihood of HIV testing. The higher the frequency of injection use in the past 3 months and the greater the level of interest in learning how to help one's partner have a safe pregnancy, the higher was the likelihood of willingness to test for HIV. Findings suggest that voluntary counselling and testing programmes need to target older married men aged 30-59 and expand services to the Northern region, where previously untested men indicated significantly higher desires of HIV testing.


Asunto(s)
Serodiagnóstico del SIDA/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Conductas Relacionadas con la Salud , Aceptación de la Atención de Salud/psicología , Esposos/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Asunción de Riesgos , Conducta Sexual , Encuestas y Cuestionarios , Uganda
18.
Technol Cancer Res Treat ; 3(2): 95-101, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15059015

RESUMEN

Cryosurgery for diverse neoplastic and non-neoplastic diseases has expanded in applicability in recent years, especially since intraoperative ultrasound became available as a method of monitoring the process of tissue freezing. However, persistence of disease after presumably adequate cryosurgical treatment has disclosed deficiencies in the technique, perhaps due to faulty application of the freeze-thaw cycles or due to shortcomings in the imaging method. Clearly cryosurgical technique is less than optimal. The optimal dosimetry for tissue freezing, the recent improvements in imaging techniques, and the need for adjunctive therapy are defined in this review, which assesses the progress toward improving the efficacy of cryosurgery.


Asunto(s)
Criocirugía/instrumentación , Criocirugía/métodos , Neoplasias/cirugía , Congelación , Humanos , Neoplasias/patología
20.
Urol Oncol ; 5(1): 11-9, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-21227280

RESUMEN

Cryosurgery for the treatment of prostatic disease, a technique that originated in the mid-1960s and was almost abandoned in the mid-1970s, has re-emerged in the 1990s for the treatment of cancer of the prostate. This renewed interest is due to several factors, including the development of intraoperative ultrasound, the refinement of percutaneous access techniques, and improvements in cryosurgical apparatus. The modern technique features the transperineal percutaneous placement of several (generally five or six) metal probes, each 3 mm in diameter, in the prostate under ultrasound guidance. After insertion, the probes are cooled in a manner that produces complete freezing of the prostate and, if required, extraprostatic extensions of disease. The freezing process is monitored by ultrasound, which provides an image of the boundary of freezing as it advances through the prostate and thereby provides control of the extent of freezing. This review describes the historical background of prostatic cryosurgery and the current status of this new procedure, including the important issues of case selection, technique, and results. The recent nature of this experience precludes judgment of long-term merit, but the favorable short-term results of cryosurgical ablation of the prostate encourage further selective use of this technique in the treatment of prostate cancer. Definition of appropriate patient selection and optimal technique are needed to improve treatment by cryosurgery.

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