Thrombotic thrombocytopenic purpura in a patient with HIV from Zimbabwe

A woman in her 40s originally from Zimbabwe presented to our accident department in the UK with a 4 day history of menorrhagia and exertional chest pain. Her clinical examination was unremarkable. Routine blood tests revealed a haemoglobin value of 6.8 g/dl and a platelet count of 15×109/l, with normal renal function and coagulation profile. Blood film showed microangiopathic haemolytic anaemia and thrombocytopenia. On direct questioning, she admitted to being HIV positive, and receiving antiviral therapy at another hospital. A diagnosis of HIV associated thrombotic thrombocytopenic purpura (TTP) was made. The patient was transferred to a tertiary centre for urgent plasma exchange. She required 8 days of 1.5 litre exchanges with solvent detergent fresh frozen plasma (FFP) and high dose steroids. She responded within 24 h with increasing haemoglobin and platelet counts, and at discharge her haemoglobin was 10.7 g/dl and platelet count 253×109/l

A clinician's guide to biosimilars in oncology

AbstractBiological agents or “biologics” are widely used in oncology practice for cancer treatment and for the supportive management of treatment-related side effects. Unlike small-molecule generic drugs, exact copies of biologics are impossible to produce because these are large and highly complex molecules produced in living cells. The term “biosimilar” refers to a biological product that is highly similar to a licensed biological product (reference or originator product) with no clinically meaningful differences in terms of safety, purity, or potency. Biosimilars have the potential to provide savings to healthcare systems and to make important biological therapies widely accessible to a global population. As biosimilars for rituximab, trastuzumab, and bevacizumab are expected to reach the market in the near future, clinicians will soon be faced with decisions to consider biosimilars as alternatives to existing reference products. The aim of this article is to inform oncology practitioners about the biosimilar development and evaluation process, and to offer guidance on how to evaluate biosimilar data in order to make informed decisions when integrating these drugs into oncology practice. We will also review several biosimilars that are currently in development for cancer treatment

Tumors Stimulate Platelet Delivery of Angiogenic Factors in Vivo

The interaction between platelets and the tumor microenvironment results in the modulation of angiogenesis, although the mechanisms governing this regulation remain unclear. This study explores the differences in the communication between wounded tissues and healthy, tumor-conditioned, and frozen platelets. Platelet-rich plasma obtained from healthy (PRP) or tumor-bearing (TPRP) mice was applied to dorsal, full-thickness wounds on diabetic mice. Wound healing was evaluated using macroscopic criteria and a staging system based on angiogenesis and stromal cell proliferation. Proteomic analysis was used to compare the levels of angiogenic proteins contained in the platelet preparations. TPRP-treated wounds reached 90% wound closure 5.6 to 9.5 days earlier than PRP-treated and nontreated wounds, respectively. TPRP induced a fourfold increase in stromal cell proliferation compared with nontreated wounds, and a 2.5-fold increase compared with PRP-treated wounds. TPRP induced the highest stimulation of angiogenesis with a fourfold increase compared with nontreated controls. On day 21, wounds treated with TPRP showed a typical architecture with thick collagen bundles. Although the levels of angiogenesis regulators detected via SELDI-ToF were similar between the PRP and TPRP treatment regimens, the enhanced healing capacity of TPRP suggests improved platelet delivery as indicated by frozen TPRP preparations that had lost most of their pro-angiogenic drive. In conclusion, these results show that intact tumor-conditioned platelets display an improved ability to deliver angiogenesis regulators to wounded tissues

Personal Relationships Across the LIfespan

Personal Relationships Across the Lifespan presents a comprehensive and up-to-date account of the role of personal relationships in people's lives. Highlighting areas of special significance and research interest at each major life-stage, Patricia Noller, Judith A. Feeney and Candida Peterson, examine how close relationships develop over time and influence individual adjustment. They explore a wide rangeof relationships, including some that are often neglected, such as those with siblings, adult children and elderly parents. They also look at alternative family forms, such as single-parent families and step-families, and address important themes such as intimacy, conflict and power. With insightful discussionof the theory and methods typically used by researchers working in this area, Personal Relationships Across the Lifespan is an ideal resource for students and researchers of both relationships and lifespan development. It will also be of interest to practitioners, such as social workers and family therapists, working with clients with relational concerns and anyone wanting to learn more about the nature of relationships

Total Syntheses of the Coumarin-Containing Natural Products Pimpinellin and Fraxetin Using Au(I)-Catalyzed Intramolecular Hydroarylation (IMHA) Chemistry

The title natural products (<b>1</b> and <b>2</b>, respectively) have been synthesized by Au­(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., <b>13</b>), which were themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)­propiolic acid or propiolic acid and <i>N</i>-(3-dimethylaminopropyl)-<i>N</i>′-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (<b>3</b>) was readily derived from fraxetin (<b>2</b>) by established procedures

Total Syntheses of the Coumarin-Containing Natural Products Pimpinellin and Fraxetin Using Au(I)-Catalyzed Intramolecular Hydroarylation (IMHA) Chemistry

The title natural products (<b>1</b> and <b>2</b>, respectively) have been synthesized by Au­(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., <b>13</b>), which were themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)­propiolic acid or propiolic acid and <i>N</i>-(3-dimethylaminopropyl)-<i>N</i>′-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (<b>3</b>) was readily derived from fraxetin (<b>2</b>) by established procedures

Total Syntheses of the Coumarin-Containing Natural Products Pimpinellin and Fraxetin Using Au(I)-Catalyzed Intramolecular Hydroarylation (IMHA) Chemistry

The title natural products (<b>1</b> and <b>2</b>, respectively) have been synthesized by Au­(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., <b>13</b>), which were themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)­propiolic acid or propiolic acid and <i>N</i>-(3-dimethylaminopropyl)-<i>N</i>′-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (<b>3</b>) was readily derived from fraxetin (<b>2</b>) by established procedures

Anti-tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma

This paper presents the work in progress of a research project that aims at establishing a reference model for 3D geo-information in the Netherlands. The research project is initiated by four national organizations: 1) Ministry of Housing, Spatial Planning and the Environment, 2) Kadaster, 3) Geonovum, and 4) the Netherlands Geodetic Commission. These four organizations responsible for geo-information in the Netherlands recognized the urgent need for a standardized approach and therefore initiated a 3D pilot. In the 3D pilot, a uniform approach for 3D geo-information modeling is explored in collaboration with a large number of stakeholders ultimately resulting in national agreements and a national standard, extending CityGML, for use of 3D geo-information. The final aim of the 3D pilot is to evoke a breakthrough in the use of 3D geo-information in the Netherlands. In the pilot providers and users of geo-information closely collaborate, which ensures that the providers are familiar with precise requirements of the users. This pilot aims also at an improved accessibility to 3D geo-information and the supporting technologies, which may push advances in 3D applications