Inotropic effect of nicardipine in patients with heart failure: Assessment by left ventricular end-systolic pressure-volume analysis

AbstractNicardipine, a new dihydropyridine calcium channel blocker, has been investigated for the treatment of coronary artery disease and heart failure. To assess the inotropic effect of nicardipine in humans independent of its vasodilator effect, equihypotensive doses of intravenous nitroprusside (mean infusion rate 65 ± 13 μg/min) and nicardipine (mean dose 5.2 ± 0.4 mg) were administered to 15 patients with heart failure (New York Heart Association functional classes II to IV, radionuclide left ventricular ejection fraction 0.15 ± 0.02). Left ventricular micromanometer pressure and simultaneous radionuclide left ventricular volume were obtained at baseline, during nitroprusside infusion, during a second baseline period and during nicardipine infusion.Heart rate did not change significantly with either nitroprusside or nicardipine. Mean systemic arterial pressure decreased by an average of 21 mm Hg with both drugs. A greater decrease in left ventricular end-diastolic pressure occurred with nitroprusside (27 ± 2 to 14 ± 2 mm Hg, p < 0.01) than with nicardipine (27 ± 2 to 23 ± 3 mm Hg, p < 0.05), and pulmonary capillary wedge pressure decreased significantly only with nitroprusside. Cardiac index increased from 1.8 ± 0.1 to 2.1 ± 0.1 liters/min per m2(p < 0.05) with nitroprusside and to a greater extent from 1.7 ± 0.1 to 2.4 ± 0.1 liters/min per m2(p < 0.01) with nicardipine. Left ventricular ejection fraction increased with nicardipine (0.15 ± 0.01 to 0.19 ± 0.01, p < 0.01), but not with nitroprusside.Peak positive first derivative of left ventricular pressure (dP/dt) decreased by 9% with both agents. Left ventricular pressure-volume loops were constructed for 14 patients. In 12 patients, the left ventricular end-systolic pressure-volume relation was shifted rightward with nicardipine, indicating a negative inotropic effect, with no shift in the remaining 2 patients.Thus, nicardipine has a negative inotropic effect in patients with heart failure. Despite this effect, left ventricular ejection fraction and cardiac index increased with nicardipine. This overall improvement in ventricular systolic performance was due to a reduction in afterload

The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop

The 1st International Workshop on Xenotropic Murine Leukemia Virus-Related Retrovirus (XMRV), co-sponsored by the National Institutes of Health, The Department of Health and Human Services and Abbott Diagnostics, was convened on September 7/8, 2010 on the NIH campus, Bethesda, MD. Attracting an international audience of over 200 participants, the 2-day event combined a series of plenary talks with updates on different aspects of XMRV research, addressing basic gammaretrovirus biology, host response, association of XMRV with chronic fatigue syndrome and prostate cancer, assay development and epidemiology. The current status of XMRV research, concerns among the scientific community and suggestions for future actions are summarized in this meeting report

Controlling a spillover pathway with the molecular cork effect

Spillover of reactants from one active site to another is important in heterogeneous catalysis and has recently been shown to enhance hydrogen storage in a variety of materials. The spillover of hydrogen is notoriously hard to detect or control. We report herein that the hydrogen spillover pathway on a Pd/Cu alloy can be controlled by reversible adsorption of a spectator molecule. Pd atoms in the Cu surface serve as hydrogen dissociation sites from which H atoms can spillover onto surrounding Cu regions. Selective adsorption of CO at these atomic Pd sites is shown to either prevent the uptake of hydrogen on, or inhibit its desorption from, the surface. In this way, the hydrogen coverage on the whole surface can be controlled by molecular adsorption at a minority site, which we term a ‘molecular cork’ effect. We show that the molecular cork effect is present during a surface catalysed hydrogenation reaction and illustrate how it can be used as a method for controlling uptake and release of hydrogen in a model storage syste

Letter to the editor: Pre-exposure prophylaxis for HIV in Europe: The need for resistance surveillance

__To the editor:__ In a recent paper by Hauser et al. in this journal, a prevalence of 10.8% of transmitted drugresistant viruses was reported among newly diagnosed HIV cases in Germany in 2013 and 2014. The authors conclude that genotypic resistance testing remains important for treatment as well as HIV prevention. We comment on the use of pre-exposure prophylaxis (PrEP) in relation to drug resistance in HIV infections and the need for European surveillance of drug resistance

Quantitative analysis of dipyridamole-thallium images for the detection of coronary artery disease

To determine if the detection of coronary artery disease by dipyridamole-thallium imaging is improved by 1) quantitative versus qualitative analysis, and 2) combining quantitative variables, 80 patients with chest pain (53 with and 27 without coronary artery disease) who underwent cardiac catheterization were studied. Segmental thallium initial uptake, linear clearance, mono-exponential clearance and redistribution were measured from early, intermediate and delayed images acquired in three projections. Normal values were determined from 13 other clinically normal subjects.When five segments per view were used for quantitative analysis, sensitivity and specificity were 87 and 63%, respectively, for uptake, 77 and 67% for linear clearance, 60 and 60% for monoexponential clearance and 62 and 56% for redistribution. Of the four variables, uptake and linear clearance were the most sensitive (p < 0.01) and specificity did not differ significantly. Using three segments per view, the specificity of uptake increased (p < 0.05) to 78% without a significant change in sensitivity (85%). With this approach, sensitivity and specificity did not differ from those of qualitative analysis (85 and 78%, respectively).Stepwise logistic regression analysis demonstrated that the best quantitative thallium correlate of the presence of coronary artery disease was a combination variable of “either abnormal uptake or abnormal linear clearance, or both.” Using five segments per view, the model's specificity (85%) was greater than that of uptake alone (p < 0.02), with similar sensitivity (92%). Using three segments per view, the model's specificity (93%) was greater than that of uptake alone (p < 0.05) and of qualitative analysis (p < 0.05), with similar sensitivity (85%). Compared with qualitative analysis, the diagnostic accuracy of the model was greater using either five segments (90 versus 82%, p < 0.01) or three segments (88 versus 82%, p < 0.05) per view.Quantitative analysis of dipyridamole-thallium images using single individual variables provides results comparable with those of qualitative analysis and this can be further optimized when a combination of quantitative variables is used

Seroprevalence of HIV, hepatitis b, and hepatitis c among opioid drug users on methadone treatment in the netherlands

Background: Injecting drug users (IDU) remain an important population at risk for blood-borne infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). In the Netherlands, a program is being implemented to offer annual voluntary screening for these infections to opioid drug users (ODUs) screened in methadone care. At two care sites where the program is now operating, our study aimed to estimate the seroprevalence among ODUs screened for HIV, HBV and HCV; to evaluate HBV vaccination coverage; and to assess the feasibility of monitoring seroprevalence trends by using routine annual screening data.Methods: Opioid drug users on methadone treatment are routinely offered voluntary screening for infectious diseases such as HIV, HBV and HCV. Data on uptake and outcome of anti-HIV, anti-HBc, and anti-HCV screening among ODUs receiving methadone were obtained from two regions: Amsterdam from 2004 to 2008 and Heerlen from 2003 to 2009.Findings: Annual screening uptake for HIV, HBV and HCV varied from 34 to 69%, depending on disease and screening site. Of users screened, 2.5% were HIV-positive in Amsterdam and 11% in Heerlen; 26% were HCV-positive in Amsterdam and 61% in Heerlen. Of those screened for HBV, evidence of current or previous infection (anti-HBc) was found among 33% in Amsterdam and 48% in Heerlen. In Amsterdam, 92% were fully vaccinated for HBV versus 45% in Heerlen.Conclusion: Annual screening for infectious diseases in all ODUs in methadone care is not fully implemented in the Netherlands. On average, more than half of the ODUs in methadone care in Heerlen and Amsterdam were screened for HIV, HBV and HCV. In addition, screening data indicate that HBV vaccination uptake was rather high. While the HIV prevalence among these ODUs was relatively low compared to other drug-using populations, the high HCV prevalence among this group underscores the need to expand annual screening and interventions to monitor HIV, HBV and HCV in the opioid drug-using population

Partner notification for reduction of HIV-1 transmission and related costs among men who have sex with men: A mathematical modeling study

Background Earlier antiretroviral treatment initiation prevents new HIV infections. A key problem in HIV prevention and care is the high number of patients diagnosed late, as these undiagnosed patients can continue forward HIV transmission. We modeled the impact on the Dutch menwho-have-sex-with-men (MSM) HIV epidemic and cost-effectiveness of an existing partner notification process for earlier identification of HIV-infected individuals to reduce HIV transmission. Methods Reduction in new infections and cost-effectiveness ratios were obtained for the use of partner notification to identify 5% of all new diagnoses (Scenario 1) and 20% of all new diagnoses (Scenario 2), versus no partner notification. Costs and quality adjusted life years (QALYs) were assigned to each disease state and calculated over 5 year increments for a20 year period. Results Partner notification is predicted to avert 18-69 infections (interquartile range [IQR] 13-24; 51-93) over the course of 5 years countrywide to 221-830 (IQR 140-299; 530-1,127) over 20 years for Scenario 1 and 2 respectively. Partner notification was considered cost-effective in the short term, with increasing cost-effectiveness over time: from €41,476 -€41, 736 (IQR €40,529-€42,147; €40,791-€42,397) to €5,773 -€5,887 (€5,134-€7,196; €5,411-€6,552) per QAL

Targeted HCV core antigen monitoring among HIV-positive men who have sex with men is cost-saving

Introduction: The World Health Organization declared the goal of hepatitis Cvirus (HCV) elimination by 2030. Micro-elimination, which is the reduction of incidence to zero in targeted populations, is less complex and costly and may be the first step to prove whether elimination is feasible. Asuitable target group are HIV-positive men who have sex with men (MSM) because of their high-risk behaviour and high incidence rates. Moreover, HCV monitoring is integrated in HIV care. The current HCV monitoring approach is suboptimal and complex and may miss new HCV infections. Alternative monitoring strategies, based on alanine aminotransferase, HCV-PCRand HCV-core antigen (HCV-cAg), combined with immediate direct-acting antiviral (DAA) treatment, may be more effective in reducing new HCV infections. Methods: Adeterministic mathematical transmission model was constructed representing the Dutch HCV epidemic among HIV-positive MSM to compare different HCV monitoring strategies from 2018 onwards. We evaluated the epidemiological impact of alternative and intensified monitoring in MSM with HCV. In addition, the cost-effectiveness was calculated over a lifetime horizon. Results: Current HCV monitoring and treatment is projected to result in an incidence of 1.1/1000 person-years, 0.24% prevalence, at a cost of 61.8 million (interquartile range 52.2-73.9). Compared with current monitoring, intensified monitoring will result in a maximum 27% reduction of incidence and 33% in prevalence at an increased cost. Conversely, compared with current monitoring, targeted HCV-cAg monitoring will result in a comparable incidence (1.1/1000 person-years) and prevalence (0.23%) but will be 1 million cheaper with increased quality-adjusted life year. Conclusion: Targeted monitoring reduces the HCV epidemic in a cost-saving manner; however, micro-elimination may not be obtained by 2030, highlighting the need for harm-reduction programmes