Niagara

The article describes Niagara Falls and the surrounding areas, including: The American Fall in Winter, Suspension Bridge, Niagara River, The Crest of the American Fall, the "Maid of the Mist", Goat Island, Prospect Park, The Horseshoe Falls from the Canadian side

Acute Myeloid Leukemia: Focus on Novel Therapeutic Strategies

Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed in the induction, post-remission and relapsed settings. The additions of clofarabine for relapsed or refractory disease and the hypomethylating agents represent recent advances. Clinical trials of FLT3 inhibitors have yielded disappointing results to date, with ongoing collaborations attempting to identify the optimal role for these agents. Potential leukemia stem cell targeted therapies and treatments in the setting of minimal residual disease are also under investigation. In this review, we will discuss recent advances in AML treatment and novel therapeutic strategies

Unilateral thalamic infarction presenting as vertical gaze palsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Vertical gaze palsy is a recognized manifestation of midbrain lesions. It rarely is a consequence of unilateral thalamic infarction.</p> <p>Case presentation</p> <p>We report the case of a 48-year-old African-American woman who presented to our facility with vertical gaze palsy and evidence of left medial thalamic infarct on diffusion-weighted imaging without coexisting midbrain ischemia. The etiology of infarct was determined to be small vessel disease after extensive investigation.</p> <p>Conclusions</p> <p>This report suggests a possible role of the thalamus as a vertical gaze control center. Clinicoradiological studies are needed to further define the role of the thalamus in vertical gaze control.</p

Study on COgnition and Prognosis in the Elderly (SCOPE)

Blood Press. 1999;8(3):177-83. Study on COgnition and Prognosis in the Elderly (SCOPE). Hansson L, Lithell H, Skoog I, Baro F, Bánki CM, Breteler M, Carbonin PU, Castaigne A, Correia M, Degaute JP, Elmfeldt D, Engedal K, Farsang C, Ferro J, Hachinski V, Hofman A, James OF, Krisin E, Leeman M, de Leeuw PW, Leys D, Lobo A, Nordby G, Olofsson B, Zanchetti A, et al. University of Uppsala, Department of Public Health, Sweden. Abstract The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by 85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged. PMID: 10595696 [PubMed - indexed for MEDLINE

Assessment of the consistency and robustness of results from a multicenter trial of remission maintenance therapy for acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>Data from a randomized multinational phase 3 trial of 320 adults with acute myeloid leukemia (AML) demonstrated that maintenance therapy with 3-week cycles of histamine dihydrochloride plus low-dose interleukin-2 (HDC/IL-2) for up to 18 months significantly improved leukemia-free survival (LFS) but lacked power to detect an overall survival (OS) difference.</p> <p>Purpose</p> <p>To assess the consistency of treatment benefit across patient subsets and the robustness of data with respect to trial centers and endpoints.</p> <p>Methods</p> <p>Forest plots were constructed with hazard ratios (HRs) of HDC/IL-2 treatment effects versus no treatment (control) for prospectively defined patient subsets. Inconsistency coefficients (I²) and interaction tests (X²) were used to detect any differences in benefit among subsets. Robustness of results to the elimination of individual study centers was performed using "leave-one-center-out" analyses. Associations between treatment effects on the endpoints were evaluated using weighted linear regression between HRs for LFS and OS estimated within countries.</p> <p>Results</p> <p>The benefit of HDC/IL-2 over controls was statistically consistent across all subsets defined by baseline prognostic variables. I²and <it>P</it>-values of X²ranged from 0.00 to 0.51 and 0.14 to 0.91, respectively. Treatment effects were statistically significant in 14 of 28 subsets analyzed. The "leave-one-center-out" analysis confirmed that no single center dominated (<it>P</it>-values ranged from 0.004 to 0.020 [mean 0.009]). The HRs representing the HDC/IL-2 effects on LFS and OS were strongly correlated at the country level (R²= 0.84).</p> <p>Limitations</p> <p>Small sample sizes in some of the subsets analyzed.</p> <p>Conclusions</p> <p>These analyses confirm the consistency and robustness of the HDC/IL-2 effect as compared with no treatment. LFS may be an acceptable surrogate for OS in future AML trials. Analyses of consistency and robustness may aid interpretation of data from multicenter trials, especially in populations with rare diseases, when the size of randomized clinical trials is limited.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00003991">NCT00003991</a></p

FDG-PET/CT in infections: the imaging method of choice?

[No abstract available

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics

Blood Press. 2000;9(2-3):146-51. Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics. Hansson L, Lithell H, Skoog I, Baro F, Bánki CM, Breteler M, Castaigne A, Correia M, Degaute JP, Elmfeldt D, Engedal K, Farsang C, Ferro J, Hachinski V, Hofman A, James OF, Krisin E, Leeman M, de Leeuw PW, Leys D, Lobo A, Nordby G, Olofsson B, Opolski G, Prince M, Reischies FM. University of Uppsala, Department of Public Health, Clinical Hypertension Research, Sweden. Abstract The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment. PMID: 10855739 [PubMed - indexed for MEDLINE

The blind men and the AML elephant:can we feel the progress?

The pharmacological therapy of non-promyelocytic acute myeloid leukemia (AML) has remained unchanged for over 40 years with an anthracycline–cytarabine combination forming the backbone of induction treatments. Nevertheless, the survival of younger patients has increased due to improved management of the toxicity of therapies including stem cell transplantation. Older patients and those with infirmity that precludes treatment-intensification have, however, not benefited from improvements in supportive care and continue to experience poor outcomes. An increased understanding of the genomic heterogeneity of AML raises the possibility of treatment-stratification to improve prognosis. Thus, efforts to identify agents with non-conventional anti-leukemic effects have paralleled those aiming to optimize leukemia cell-kill with conventional chemotherapy, resulting in a number of randomized controlled trials (RCT). In the last 18 months, RCTs investigating the effects of vosaroxin, azacitidine and gemtuzumab ozogamycin and daunorubicin dose have been reported with some studies indicating a statistically significant survival benefit with the investigational agent compared with standard therapy and potentially, a new era in AML therapeutics. Given the increasing costs of cancer care, a review of these studies, with particular attention to the magnitude of clinical benefit with the newer agents would be useful, especially for physicians treating patients in single-payer health systems