Hyperhaploid clones (24-34 chromosomes) were identified in 33 patients with multiple myeloma (MM), identifying a novel numerical cytogenetic subgroup. Strikingly, all hyperhaploid karyotypes were found to harbor monosomy 17p, the single most important risk stratification lesion in MM. A catastrophic loss of nearly a haploid set of chromosomes results in disomies of chromosomes 3, 5, 7, 9, 11, 15, 18, 19, and 21, the same basic set of odd-numbered chromosomes found in trisomy in hyperdiploid myeloma. All other autosomes are found in monosomy, resulting in additional clinically relevant monosomies of 1p, 6q, 13q, and 16q. Hypotriploid subclones (58-68 chromosomes) were also identified in 11 of the 33 patients and represent a duplication of the hyperhaploid clone. Analysis of clones utilizing interphase fluorescence in-situ hybridization (iFISH), metaphase FISH, and spectral karyotyping identified either monosomy 17 or del17p in all patients. Amplification of 1q21 was identified in eight patients, demonstrating an additional high-risk marker. Importantly, our findings indicate that current iFISH strategies may be uninformative or ambiguous in the detection of these clones, suggesting this patient subgroup maybe under-reported. Overall survival for patients with hyperhaploid clones was poor, with a five-year survival rate of 23.1%. These findings identify a distinct numerical subgroup with cytogenetically defined high-risk disease.
Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.
Introduction: When enrollment in SAMMPRIS was stopped, the 30-day rate of stroke or death and the 1-year rate of the primary endpoint in the medical arm were 5.8% and 12.2%, respectively. The comparative rates in patients in WASID who met the SAMMPRIS entry criteria were 10.6% and 21.9%. While the lower rates in the SAMMPRIS trial have been attributed to aggressive medical management, an alternative hypothesis is that SAMMPRIS patients may have been at lower risk due to a lower burden of vascular risk factors. Methods: We compared risk factors at study entry in the 227 patients in the medical arm of SAMMPRIS with the 143 patients in WASID who met the SAMMPRIS entry criteria. Results: Compared with WASID patients, SAMMPRIS patients were younger (mean age 59.5 years vs. 62.5 years; p=0.009) but had higher percentages of hypertension (89% vs. 76%; p<0.001)*, hyperlipidemia (89% vs 69%; p<0.001)*, stenosis in the 80-99% range (55% vs. 35%; p<0.001), anterior circulation stenosis (68% vs. 48%; p<0.001), white race (71% vs. 61%; p=0.06), and on an antithrombotic agent at the time of the qualifying event (62% vs. 52%; p=0.08). SAMMPRIS patients had higher mean systolic blood pressure (146.8 mmHg vs. 139.1, p< 0.001), higher body mass index (30.7 kg/m 2 vs. 29.4, p=0.045) but lower LDL (98 mg/dl vs. 125, p<0.001). There were no significant differences in the frequency of female gender, stroke as the qualifying event, diabetes, smoking, history of previous stroke, time from qualifying event to study entry, and history of CAD. Conclusion: Compared to WASID patients meeting the SAMMPRIS entrance criteria, SAMMPRIS patients were slightly younger but had a higher burden of other important vascular risk factors including severity of stenosis, which was the most important predictor of subsequent stroke in WASID. These data suggest that the improved prognosis in the medical arm of SAMMPRIS compared with WASID patients is related to the aggressive medical management used in SAMMPRIS and not to a lower burden of risk factors in SAMMPRIS patients. * the increased frequency of hypertension and hyperlipidemia in SAMMPRIS might reflect the change in the JNC definition of hypertension after the start of WASID and the fact that many more patients are prescribed statins now than when WASID was done
A widely influential but oft-neglected figure, Henri Grégoire participated in the Enlightenment, French Revolution, and Restoration periods with equal facility and influence. While most analyses of Grégoire have focused on specific époques or events, Sepinwall, in this highly contextualized study, argues for the importance of treating the whole of Grégoire's work and thought together in one study. Significantly, Sepinwall asserts the continuity of Grégoire's thought across the divide of the French Revolution. Through an exploration of several key issues -namely, the origins of the French Revolution and the relationship between Christianity and Enlightenment, the revolutionary idea of universalism, and the legacy of the Revolution to the present -Sepinwall uses Grégoire to illuminate shifts in old regime thought as well as a number of historiographical trends in French history.The author divides Grégoire's life into three large categories. The first section explores Grégoire's intellectual development, his early influences and jobs, and his interest in Judaism. The son of a tailor, Grégoire overcame the odds to gain an education in theology and earn a lucrative and important post in Emberménil. His education and success placed him amid the elite of Lorraine and, in particular, a set of people who had formed the Société des Philantropes of Strasbourg. This quasi-Masonic group fostered the Enlightenment movement in Lorraine. Thus, Grégoire found an outlet for the expression of some of his ideas about the importance of Christianity, as well as the place of Jews in French society. Grégoire also encouraged the education of peasants, the elimination of the local patois, and church reform. In addition, he wrote a response to an essay contest proposed by the Société royale des sciences et des arts de Metz which asked, 'Are there ways of making the Jews more useful and happier in France?' His solution called for the regeneration of the Jews, a concept that would continue to occupy Grégoire's thinking into the Revolution and beyond.The second section of the book, 'Grégoire in Paris', explores the abbé's role during the period of the French Revolution. Elected a deputy to the Estates-General, Grégoire dutifully headed for Versailles in May 1789 where he quickly earned a reputation as a leader. Most famously, Grégoire appears front and centre in Jacques-Louis David's painting of the 'Tennis Court Oath'. These tumultuous times allowed Grégoire the opportunity to apply his interests in religion and Enlightenment. He expanded his earlier thinking about regeneration to include a wider group of people, including non-whites and Jews (but not women), and argued that the strength of the French nation depended on transforming as many of its people as possible into citizens. He veered from the revolution somewhat, however, over the question of the role of religion. Grégoire continued to argue for the centrality of religion in France, while others moved toward the idea of a de-Christianized state.The last section of the book, 'Keeping t...
In the last 12 months or so, particularly with the drop in oil price, there’s been a lot of speculation about the future of the Australian oil and gas industry. Strenuous efforts are being made to bring down costs, reduce complexity and expedite the completion of major capital projects. Yet with the commodity price looking likely to be subdued for some time, serious questions persist. How can we sustain activity in Australia, secure the investment needed to continue exploration and appraisal drilling, for the next wave of projects? In looking for answers to these challenges, collaboration is a theme that comes up time and time again. But what does it actually mean? What does it look like in practice? Who does it well and how? And which companies are reaping the rewards of great collaboration? To fill this knowledge gap we are launching a survey which will look at many aspects of collaboration in the Australia and compare this with the results of similar surveys conducted in the UK. We will be looking to survey both operators and service companies working in the Australia and find out: What does collaboration mean? What constitutes effective collaboration? How do companies view themselves and each other as collaborators? How does collaboration in Australia compare with companies in the North Sea? We hope a better understanding of collaboration could help companies in Australia continue to improve productivity and efficiency, adopt new ways of working, and truly make the most of Australia’s abundant resources.
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