Three Decades of Ultrasound Contrast Agents: A Review of the Past, Present and Future Improvements.

Initial reports from the 1960s describing the observations of ultrasound contrast enhancement by tiny gaseous bubbles during echocardiographic examinations prompted the development of the first ultrasound contrast agent in the 1980s. Current commercial contrast agents for echography, such as Definity, Optison, Sonazoid and SonoVue, have proven to be successful in a variety of on- and off-label clinical indications. Whereas contrast-specific technology has seen dramatic progress after the introduction of the first approved agents in the 1990s, successful clinical translation of new developments has been limited during the same period, while understanding of microbubble physical, chemical and biologic behavior has improved substantially. It is expected that for a successful development of future opportunities, such as ultrasound molecular imaging and therapeutic applications using microbubbles, new creative developments in microbubble engineering and production dedicated to further optimizing microbubble performance are required, and that they cannot rely on bubble technology developed more than 3 decades ago.

Fowler's Solution and the Evolution of the Use of Arsenic in Modern Medicine.

While arsenic has been used medicinally and as a poison for thousands of years, Fowler's solution, an arsenic compound, has had a fascinating history in medicine during the past 200 years. The use of Fowler's solution was first described and published as a treatment for malaria and syphilis in the late 1700s. Many clinical applications for Fowler's solutions have been studied and utilized over the years, but toxicities have limited its utility. Even so, arsenic trioxide, chemically related to Fowler's solution, was approved by the US Food and Drug Administration for treating acute promyelocytic leukemia. The history of Fowler's solution, its applications and uses, and benefits and risks are discussed.

Historic air pollution exposure and long-term mortality risks in England and Wales: prospective longitudinal cohort study.

INTRODUCTION: Long-term air pollution exposure contributes to mortality but there are few studies examining effects of very long-term (>25 years) exposures. METHODS: This study investigated modelled air pollution concentrations at residence for 1971, 1981, 1991 (black smoke (BS) and SO2) and 2001 (PM10) in relation to mortality up to 2009 in 367,658 members of the longitudinal survey, a 1% sample of the English Census. Outcomes were all-cause (excluding accidents), cardiovascular (CV) and respiratory mortality. RESULTS: BS and SO2 exposures remained associated with mortality decades after exposure-BS exposure in 1971 was significantly associated with all-cause (OR 1.02 (95% CI 1.01 to 1.04)) and respiratory (OR 1.05 (95% CI 1.01 to 1.09)) mortality in 2002-2009 (ORs expressed per 10 µg/m(3)). Largest effect sizes were seen for more recent exposures and for respiratory disease. PM10 exposure in 2001 was associated with all outcomes in 2002-2009 with stronger associations for respiratory (OR 1.22 (95% CI 1.04 to 1.44)) than CV mortality (OR 1.12 (95% CI 1.01 to 1.25)). Adjusting PM10 for past BS and SO2 exposures in 1971, 1981 and 1991 reduced the all-cause OR to 1.16 (95% CI 1.07 to 1.26) while CV and respiratory associations lost significance, suggesting confounding by past air pollution exposure, but there was no evidence for effect modification. Limitations include limited information on confounding by smoking and exposure misclassification of historic exposures. CONCLUSIONS: This large national study suggests that air pollution exposure has long-term effects on mortality that persist decades after exposure, and that historic air pollution exposures influence current estimates of associations between air pollution and mortality.

The emerging role of arsenic trioxide as an immunomodulatory agent in the management of multiple myeloma.

Multiple myeloma is a clonal disorder of plasma cells which is considered incurable with currently available therapies. Substantial advances have been achieved in the past decade with the identification of cellular mechanisms that confer drug resistance. This has resulted in newer agents such as arsenic trioxide (Trisenoxt), lenalidomide (Revlimid) and bortezomib (Velcade) with promising activity in this disease. In this review article we will outline the history, mechanisms of action, pharmacology, and clinical trials of arsenic trioxide in multiple myeloma.

How acute promyelocytic leukaemia revived arsenic.

Despite its many therapeutic qualities, arsenic trioxide has been more commonly remembered as Madame Bovary's poison than as an anticancer drug. The ability of arsenic trioxide to treat acute promyelocytic leukaemia has radically changed this view, providing new insights into the pathogenesis of this malignancy and raising hopes that arsenicals might be useful in treating other cancers.

Introduction: the history of arsenic trioxide in cancer therapy.

Although arsenic can be poisonous, and chronic arsenic exposure from industrial or natural sources can cause serious toxicity, arsenic has been used therapeutically for more than 2,400 years. Thomas Fowler's potassium bicarbonate-based solution of arsenic trioxide (As(2)O(3)) was used empirically to treat a variety of disorders, and in 1878, was reported to reduce white blood cell counts in two normal individuals and one with "leucocythemia." Salvarsan, an organic arsenical for treating syphilis and trypanosomiasis, was developed in 1910 by Paul EHRLICH: In the 1930s, arsenic was reported to be effective in chronic myelogenous leukemia. After a decline in the use of arsenic during the mid-20th century, reports from China described a high proportion of hematologic responses in patients with acute promyelocytic leukemia (APL) who were treated with arsenic trioxide. Randomized clinical trials in the U.S. led to FDA approval of arsenic trioxide for relapsed or refractory APL in September 2000.