Are Human Embryos One of Us? An Exploration of Personhood

This article was originally an address presented by Dr. James Rusthoven at Dordt College, April 12, 2007

Rhodotorula fungaemia: a life-threatening complication of indwelling central venous catheters

Eine 30-jÄhrige Frau, wegen einer intestinalen MotilitÄtsstÖrung Über einen zentralvenÖsen Verweilkatheter vollstÄndig parenteral ernÄhrungspflichtig, entwickelte Fieber, Tachykardie, Tachypnoe und Hypotonie. Aus mehrmaligen Blutkulturen, Über den Katheter vor dem Auftreten dieser Symptome gewonnen, sowie aus einer davor angelegten peripheren Blutkultur wurde die rote Hefe Rhodotorula rubra angezÜchtet. Die Patientin verblieb Über einen Monat lang in kritischem Zustand, erholte sich jedoch unter Therapie mit den systemischen Antimykotika Amphotericin B und Flucytosin und nach Entfernung des Katheters. Obgleich Rhodotorula allgemein als nur geringgradig pathogen angesehen wird, belegt dieser Fall den ernsthaften Charakter der Rhodotorula -Sepsis sowie die Notwendigkeit der systemischen Antimykotika-Therapie und der Entfernung des Katheters. Summary . A 30-year-old woman receiving total parenteral nutrition via an indwelling central venous catheter for an intestinal motility disorder developed fever, tachycardia, tachypnea, and hypotension. Multiple blood cultures drawn through the catheter prior to these events, as well as a peripheral blood culture obtained earlier, grew the red yeast Rhodotorula rubra . The patient was critically ill for over one month but eventually recovered with therapy including the systemic antifungal agents amphotericin B and flucytosine and removal of the catheter. Although Rhodotorula has generally been regarded as having low pathogenicity, this case emphasizes the serious nature of Rhodotorula sepsis and suggests the need for both systemic antifungal therapy and removal of a colonized indwelling catheter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73949/1/j.1439-0507.1992.tb00882.x.pd

Strategies to Preserve Cognition in Patients With Brain Metastases: A Review

Brain metastases are common to the natural history of many advanced malignancies. Historically, whole brain radiation therapy (WBRT) has played a key role in the management of brain metastases, especially for patients with multiple lesions. However, prospective trials have demonstrated consistent neurocognitive toxicities after WBRT, and various pharmacologic and anatomic strategies designed to mitigate these toxicities have been studied in recent years. Memantine, an NMDA receptor antagonist, taken during and after WBRT improved cognitive preservation in a randomized trial over placebo. Deliberate reductions in radiation dose to the hippocampus, via hippocampal-avoidance (HA)-WBRT, resulted in improved cognition over historic controls in a phase II trial, and follow-up randomized trials are now ongoing to evaluate cognitive outcomes with HA vs. conventional brain radiation techniques. Nevertheless, some of the most promising strategies currently available to reduce the cognitive effects of brain radiation may be found in efforts to avoid or delay WBRT administration altogether. Stereotactic radiosurgery (SRS), involving focused, high-dose radiation to central nervous system (CNS) lesions with maximal sparing of normal brain parenchyma, has become the standard for limited brain metastases (classically 1–3 or 4 lesions) in the wake of multiple randomized trials demonstrating equivalent survival and improved cognition with SRS alone compared to SRS plus WBRT. Today, there is growing evidence to support SRS alone for multiple (≥4) brain metastases, with comparable survival to SRS alone in patients with fewer lesions. In patients with small-cell lung cancer, the routine use of prophylactic cranial irradiation (PCI) for extensive-stage disease has been also been challenged following the results of a randomized trial supporting an alternative strategy of MRI brain surveillance and early salvage radiation for the development of brain metastases. Moreover, new systemic agents are demonstrating increasing CNS penetration and activity, with the potential to offer greater control of widespread and microscopic brain disease that was previously only achievable with WBRT. In this review, we endeavor to put these clinical data on cognition and brain metastases into historical context and to survey the evolving landscape of strategies to improve future outcomes

The effect of SH3 domains on dynamin activity and oligomerisation

Dynamin is a GTPase enzyme that mediates vesicle fission during endocytosis to release new vesicles into the cell cytoplasm. It is recruited to sites of endocytosis in cells where it promotes vesicle fission by assembling into a collar around the vesicle neck. Dynamin is regulated by binding to proteins containing src homology 3 (SH3) domain, which stimulate its oligomerisation into rings with an associated increase in dynamin GTPase activity. However, each SH3 domain has been inconsistently studied in isolation from the others and sometimes as part of the full-length protein. This study revealed important new insights into dynamin modulation, isoform functional diversity and therefore potential function in endocytosis. Through a systematic approach, the observations overturn conclusions of several previous studies and reveal many new insights into dynamin activation and the remarkable diversity in the way SH3 domains stimulate dynamin. The existence of a previously unknown assembly independent allosteric mechanism to stimulate dynamin GTPase is revealed. The work highlights the SH3 domain of SNX9 as the most potent and consistent in vitro regulator of dynamin oligomerisation and activity. It also mapped the unique binding mechanism for SNX9 on dynamin I and revealed that this interaction is potentially phospho-regulated

Reply to 'Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma : a systematic review and meta-analysis''

Non peer reviewe

Multiple Masses on the Tongue of a Patient with Generalized Mucocutaneous Lesions

Luca Pastore and colleagues discuss the differential diagnosis and management of a 62-year-old man who presented with a 6-cm fungating mass on the dorsum of the tongue

Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): Study protocol for a randomized phase II trial

<p>Abstract</p> <p>Background</p> <p>Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone.</p> <p>Methods</p> <p>After stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy.</p> <p>Discussion</p> <p>This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study.</p> <p>Trial registration</p> <p>Clinicaltrials.gov identifier: NCT01446744</p

Pathological vertebral fracture after stereotactic body radiation therapy for lung metastases. Case report and literature review.

<p>Abstract</p> <p>Background</p> <p>Stereotactic body radiation therapy (SBRT) is a radiation technique used in patients with oligometastatic lung disease. Lung and chest wall toxicities have been described in the patients but pathological vertebral fracture is an adverse effect no reported in patients treated with SBRT for lung metastases.</p> <p>Case presentation</p> <p>A 68-year-old woman with the diagnosis of a recurrence of a single lung metastatic nodule of urothelial carcinoma after third line of chemotherapy. The patient received a hypo-fractionated course of SBRT.A 3D-conformal multifield technique was used with six coplanar and one non-coplanar statics beams. A total dose of 48 Gy in three fractions over six days was prescribed to the 95% of the CTV. Ten months after the SBRT procedure, a CT scan showed complete response of the metastatic disease without signs of radiation pneumonitis. However, rib and vertebral bone toxicities were observed with the fracture-collapse of the 7^thand 8^thvertebral bodies and a fracture of the 7^thand 8^thleft ribs. We report a unique case of pathological vertebral fracture appearing ten months after SBRT for an asymptomatic growing lung metastases of urothelial carcinoma.</p> <p>Conclusion</p> <p>Though SBRT allows for minimization of normal tissue exposure to high radiation doses SBRT tolerance for vertebral bone tissue has been poorly evaluated in patients with lung tumors. Oncologists should be alert to the potential risk of fatal bone toxicity caused by this novel treatment. We recommend BMD testing in all woman over 65 years old with clinical risk factors that could contribute to low BMD. If low BMD is demonstrated, we should carefully restrict the maximum radiation dose in the vertebral body in order to avoid intermediate or low radiation dose to the whole vertebral body.</p