Addition of a topoisomerase I inhibitor to trimodality therapy [cis-diamminedichloroplatinum(II)/heat/radiation] in a murine tumor

The cytotoxicity of the topoisomerase I inhibitors, camptothecin and topotecan, toward exponentially growing EMT-6 murine mammary carcinoma cells under various conditions of oxygenation, pH and temperature was assessed. Under normal pH (pH 7.40) conditions both camptothecin and topotecan were more cytotoxic toward normally oxygenated cells. Both agents were more cytotoxic under acidic pH (pH 6.45) and the differential in cytotoxicity due to the cellular oxygenation level disappeared. Neither camptothecin nor topotecan was enhanced in cytotoxicity by hyperthermia (42°C or 43°C, 60 min) during drug exposure. Both camptothecin and topotecan killed increasing numbers of FSaIIC tumor cells with increasing dose of the drugs in vivo in a log/linear manner. Local hyperthermia (43°C, 30 min) increased the tumor cell killing of the drugs but decreased the toxicity of these agents to the bone marrow granulocyte/macrophage-colony-forming units. Topotecan was a more effective modulator of cisplatin than was camptothecin, as determined by FSaIIC tumor cell survival assay and by FSaIIC tumor growth delay. Although both camptothecin and topotecan were effective additions to a treatment regimen including cisplatin and daily fractionated radiation (5×3Gy), neither of these topoisomerase I inhibitors increased the tumor growth delay produced by the trimodality regimen of cisplatin/hyperthermia/radiation.Abbreviations Cisplatin cis-diamminedichloroplatinum(II) - GM-CFU granulocyte-macrophage progenitor colony-forming unit This work was supported by NCI grants RO1-47379 and RO1-50174     

Structures,processes and outcomes of the Aussie Heart Guide Program: A nurse mentor supported,home based cardiac rehabilitation program for rural patients with acute coronary syndrome

Background

Cardiac rehabilitation has a number of benefits for patients, yet participation in it is sub-optimal, especially in regional Australia. Innovative models of cardiac rehabilitation are needed to improve participation. Providing nurse mentors to support patients transitioning from hospital to home represents a new model of service delivery in Australia.

Point-of-care diagnostics for respiratory viral infections

Introduction: Successful treatment outcomes for viral respiratory tract infections presenting from primary health care to quaternary hospitals will only be achieved with rapid, sensitive and specific identification of pathogens to allow effective pathogen-specific antiviral therapy and infection control measures.

Areas covered: This review aims to explore the different point-of-care tests currently available to diagnose viral respiratory tract infections, discuss the advantages and limitations of point-of-care testing, and provide insights into the future of point-of-care tests. The following databases were searched: Medline (January 1996 to 30 September 2017) and Embase (1988 to 30 September 2017), using the following keywords: ‘point of care’, ‘respiratory virus’, ‘influenza’, ‘RSV’, ‘diagnostics’, ‘nucleic acid test’ and ‘PCR’.

Expert commentary: Viral respiratory tract infections cause significant morbidity and mortality worldwide, and point-of-care tests are facilitating the rapid identification of the pathogen responsible given the similarities in clinical presentation.     

Association with right atrial strain with right atrial pressure: an invasive validation study

Echocardiographic assessment of right atrial pressure (RAP) from inferior vena cava (RAP_IVC) dimension may underestimate catheter-derived (RAP_C). As right atrial (RA) deformation, measured by speckle tracking, is preload-dependent, we hypothesized that RA strain may improve estimation of RAP_C. Right atrial strain components [RA reservoir function (?R), peak RA contraction (?CT) and RA conduit function (?CD)] were measured in 125 of 175 patients who had echocardiography and invasive measures of RAP (median difference 1 day). To determine whether RA strain measures differentiated patients with correct vs incorrect RAP_IVC assessment, categories with RAP_IVC values?<?3, 8 and >?15 mmHg were compared with RAP_C groups?<?3, 4–7, 8–10, 11–14 and >?15 mmHg. Non-invasively determined RAP was significantly lower (p?=?0.001) than invasively determined RAP_C, with a weak correlation (r?=?0.35, p?<?0.001). RA strain components were associated with RA size, RV function and IVC size. In those with RAP_IVC?>?15 mmHg, half of patients were categorized into RAP?<?10 mmHg. There were no significant differences in RA characteristics that differentiated patients in whom echocardiographic estimation of RAP was inaccurate. Right atrial strain measures were feasible, and had associations with RA size, RV systolic function and IVC size. Right atrial strain was significantly different between those with normal vs raised pressure, but it did not identify those with incorrect echocardiographic assessment of RAP.     

Using Pharmacies in a Structural Intervention to Distribute Low Dead Space Syringes to Reduce HIV and HCV Transmission in People Who Inject Drugs

Ongoing injection drug use contributes to the HIV and HCV epidemics in people who inject drugs. In many places, pharmacies are the primary source of sterile syringes for people who inject drugs; thus, pharmacies provide a viable public health service that reduces blood-borne disease transmission.Replacing the supply of high dead space syringes with low dead space syringes could have far-reaching benefits that include further prevention of disease transmission in people who inject drugs and reductions in dosing inaccuracies, medication errors, and medication waste in patients who use syringes.We explored using pharmacies in a structural intervention to increase the uptake of low dead space syringes as part of a comprehensive strategy to reverse these epidemics.There are approximately 1.1 million people living with HIV in the United States.1 Over the past decade, the HIV incidence rate among people who inject drugs (PWID) has decreased; however, PWID remain disproportionately affected by HIV. It is estimated that 8% of new HIV cases in 2010 were among PWID.1 Co-occurring is the HCV epidemic; approximately 2.7 million people are chronically infected with HCV.2 Studies estimate that the prevalence of HCV among PWID ranges from 40% to 90%.3,4 Ongoing injection drug use and injection risk behaviors contribute to both epidemics.Although effective therapies exist, ultimately, preventing the transmission of HIV and HCV is essential to ending these epidemics, particularly in high-risk populations. PWID constitute a vulnerable population that faces numerous economic and personal barriers (e.g., comorbidities) that prevent them from receiving appropriate medical care.5,6 Public health resources and interventions that focus on the prevention of HIV and HCV in PWID are needed.Multiperson use of needles and syringes (i.e., direct sharing) and multiperson use of drug preparation materials (i.e., indirect sharing) are important risk factors for infection acquisition and transmission among PWID.7 An estimated 50% to 80% of PWID acquire HCV infection within the first year of injection drug use.8 Recommended interventions to discourage injection drug use include risk-reduction programs and substance abuse treatment.9 However, because of limited awareness of available programs, lack of access to treatment facilities, need for program referral, and cost of treatment, many PWID are unable to stop injecting drugs.7 A well-known public health measure to reduce the spread of infection is to promote the use of sterile syringes.10 We explored using pharmacies in a structural intervention to help prevent the transmission of HIV and HCV through syringes.     

Diagnosing centrally located pulmonary embolisms in the emergency department using point-of-care ultrasound

Objective

The study objective was to investigate the combined accuracy of right heart strain on focused cardiac ultrasound (FOCUS) and deep vein thrombosis (DVT) on compression ultrasound (CUS) for identification of centrally located pulmonary embolism (PE) diagnosed on computed tomography pulmonary angiography (CTPA).

Positive association between beta-chemokine-producing T cells and HIV type 1 viral load in HIV-infected subjects in Abidjan, Côte d'Ivoire

The role of beta-chemokines in controlling HIV replication in vivo is still controversial. Therefore, the association between HIV-1 plasma viral load and the capacity of CD4(+) and CD8(+) T cells to produce beta-chemokines was studied in 28 antiretroviral drug-na?ve HIV-1-infected female sex workers in Abidjan, C?te d'Ivoire. Percentages of beta-chemokine-positive T cells were measured in peripheral blood mononuclear cells by flow cytometry after intracellular staining for RANTES (regulated on activation, normal T expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. HIV-1-infected subjects had higher percentages of MIP-1alpha- and MIP-1beta-positive CD4(+) and CD8(+) T cells (p < 0.02) and of RANTES-positive CD8(+) T cells (p = 0.054) than uninfected controls. Percentages of RANTES- and MIP-1beta-positive CD8(+) T cells correlated directly with HIV-1 plasma viral load (p < 0.02). Percentages of beta-chemokine-positive CD4(+) and CD8(+) T cells correlated directly with percentages of HLA-DR-positive T cells (p < 0.02) and inversely (except RANTES in CD4(+) T cells) with absolute numbers of CD4(+) T cells (p < 0.05) in peripheral blood. These data indicate that increased percentages of beta-chemokine-producing T cells in HIV-1-infected subjects correlate with disease progression and are a sign of viremia-driven chronic T cell activation.     

In vivo and in vitro evidence of B cell hyperactivity during Lyme disease

In vitro IgM production by cells from patients with Lyme disease rose during the illness in those studied soon after onset, but fell from elevated levels in those initially studied later than 1 week after onset. Borrelia burgdorferi stimulated normal and patients' cells produced IgM, with cells from acutely ill patients producing the most; production fell during convalescence. Patients with active Lyme disease and those destined for later manifestations often had serum agglutinins for heterologous red blood cells. Thus, there is in vitro and in vivo B cell hyperactivity in Lyme disease caused by B. burgdorferi. Both mitogenic and antigenic stimulation of B cells may induce the humoral response seen in complicated Lyme disease.