In‐hospital worsening heart failure

Acute worsening heart failure (WHF) is seen in a sizable portion of patients hospitalized for heart failure, and is increasingly being recognized as an entity that is associated with an adverse in‐hospital course. WHF is generally defined as worsening heart failure symptoms and signs requiring an intensification of therapy, and is reported to be seen in anywhere from 5% to 42% of heart failure admissions. It is difficult to ascertain the exact epidemiology of WHF due to varying definitions used in the literature. Studies indicate that WHF cannot be precisely predicted on the basis of baseline variables assessed at the time of admission. Recent data suggest that some experimental therapies may reduce the risk of development of WHF among hospitalized heart failure patients, and this is associated with a reduction in risk of subsequent post‐discharge cardiovascular mortality. In this respect, WHF holds promise as a endpoint for acute heart failure clinical trials to better elucidate the benefit of targeted novel therapies. Better understanding of the pathophysiology and a consensus on the definition of WHF will further improve our epidemiological and clinical understanding of this entity.     

Decompensated heart failure: is there a role for the outpatient use of nesiritide?

Heart failure (HF) management has seen enormous advances in the past two decades, including publication of HF management guidelines targeted at further reduction of morbidity and mortality. Nonetheless, the morbidity of HF has steadily increased and now represents one of the largest health care expenditures in this country. Because hospitalization for HF is most likely for patients with more advanced HF, they share a disproportionate burden of the hospitalization costs and will require treatment regimens beyond the current guidelines, if this burden is to be alleviated. In June 2004, a group of investigators who helped establish the natriuretic peptide treatment paradigm, met to discuss the potential role of nesiritide as an outpatient treatment option for patients with symptomatic HF who were at high risk for repeated admissions, a syndrome now described as "chronic decompensated HF." This report presents their considerations on the contribution of natriuretic peptide physiology to the amelioration of progressive left ventricular dysfunction, the therapeutic use of B-type natriuretic peptide, and its potential application to the outpatient management of acute and chronic decompensated HF. The use of outpatient IV nesiritide was considered a promising treatment option for symptomatic chronic decompensated HF patients that merits further investigation. Such an approach, once validated, should be integrated into an evidence-based HF disease management program.     

State of the art: using natriuretic peptide levels in clinical practice

Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians:     

Antigenic determinants of the attachment protein of Mycoplasma pneumoniae shared by other pathogenic Mycoplasma species.

In previous studies with hyperimmune rabbit antisera, we found evidence of serologic cross-reactivity among Mycoplasma pneumoniae, Mycoplasma genitalium, and Mycoplasma gallisepticum. Because of certain biologic and morphologic similarities of these species, attempts were made to determine if this cross-reactivity related to the attachment protein (P1) of M. pneumoniae. Monoclonal and monospecific antibodies against P1 were used to probe proteins of the other species by immunoblotting. One of the P1 monoclonal antibodies was reactive with a smaller protein of M. genitalium; rabbit antiserum raised by immunization with P1 excised from a sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel was found to react with a similar-sized protein of M. gallisepticum. These preliminary findings suggest antigenic sharing among the species examined; however, limitations of the methods used are discussed.     

Assay of digitalis glycosides in man

The administration of digitalis glycosides is followed by a consistent and dose-dependent abbreviation of the duration of left ventricular ejection in normal individuals. The changes in left ventricular ejection time determined from the indirect carotid arterial tracing and corrected for heart rate (ejection time index) offer an easily derived measure of the myocardial response to digitalis. In the present studies, this effect of the cardiac glycosides was employed in comparing the temporal course of the action of four digitalis glycosides in man.

Deslanoside (1.6 mg.) and ouabain (1.0 mg.) intravenously induced a temporally equivalent onset of action which reached a maximum 20 minutes after administration. Onset of the effect of digoxin (1.6 mg. intravenously) was similarly rapid. The initial response to digoxin was followed by a secondary delayed effect which reached its maximum six hours after drug administration. Digitoxin (1.6 mg. intravenously) evoked a slight initial effect followed by a slowly developing, late response which reached a maximum six hours after its administration. A logarithmic temporal dissipation of the effects of the digitalis glycosides on the ejection time index occurred. From the dissipation curves the physiologic half-lives of the glycosides were calculated: ouabain, 22 hour; digoxin, 33 hour; deslanoside, 36 hour; and digitoxin, 102 to 112 hour. When administered orally, digoxin elicited a response characterized by a late onset, delayed maximum and diminished potency when compared to the intravenously administered agent. The effects of digitoxin on the ejection time index were virtually identical by the intravenous and oral routes.

The action of digitalis glycosides on ejection time index was demonstrated in patients with heart failure and in individuals with complete heart block. These effects on ejection time index offer a new, objective and quantitative approach to the measurement of the cardiac response to digitalis in man.     

Influence of wet surfaces and fall height on pediatric injury risk in feet-first freefalls as predicted using a test dummy

INTRODUCTION: Falls are a major cause of morbidity and mortality in children, but are also reported falsely in child abuse. Therefore, it is of interest to understand those factors which may lead to a higher likelihood of injury in a feet-first freefall. METHODS: We used laboratory freefall experiments and a 3-year-old Hybrid III anthropomorphic test dummy (ATD) to assess head and femur injury risk. Wet and dry linoleum impact surfaces were used from three fall heights: 22, 35 and 47 in. RESULTS: For a given fall height, dry surfaces were associated with higher head injury criteria (HIC) values than wet surfaces. Changes in fall height 22-47 in. did not significantly affect HIC values for falls onto either surface. Generally, compressive and bending femur loading increased significantly for wet as compared to dry linoleum. CONCLUSIONS: In simulated feet first freefall experiments up to 47 in. using a 3-year-old test dummy, a low risk of contact type head injury and femur fracture was found. However, both fall height and surface conditions influenced femur loading and head injury measures. Future efforts should explore the risk of head injury associated with angular acceleration in freefalls.     

Identification of oseltamivir resistance among pandemic and seasonal influenza A (H1N1) viruses by an His275Tyr genotyping assay using the cycling probe method

Neuraminidase inhibitors are agents used against influenza viruses; however, the emergence of drug-resistant strains is a major concern. Recently, the prevalence of oseltamivir-resistant seasonal influenza A (H1N1) virus increased globally and the emergence of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses was reported. In this study, we developed a cycling probe real-time PCR method for the detection of oseltamivir-resistant seasonal influenza A (H1N1) and pandemic influenza A (H1N1) 2009 viruses. We designed two sets of primers and probes that were labeled with 6-carboxyfluorescein or 6-carboxy-X-rhodamine to identify single nucleotide polymorphisms (SNPs) that correspond to a histidine and a tyrosine at position 275 in the neuraminidase protein, respectively. These SNPs confer susceptibility and resistance to oseltamivir, respectively. In the 2007-2008 season, the prevalence of oseltamivir-resistant H1N1 viruses was 0% (0/72), but in the 2008-2009 season, it increased to 100% (282/282). In the 2009-2010 season, all of the pandemic influenza A (H1N1) 2009 viruses were susceptible to oseltamivir (0/73, 0%). This method is sensitive and specific for the screening of oseltamivir-resistant influenza A (H1N1) viruses. This method is applicable to routine laboratory-based monitoring of drug resistance and patient management during antiviral therapy.     

Physiological and metabolic responses of female games and endurance athletes to prolonged, intermittent, high-intensity running at 30° and 16°C ambient temperatures

Eight female games players (GP) and eight female endurance athletes (EA) ran intermittently at high-intensity and for prolonged periods in hot (30°C) and moderate (16°C) ambient temperatures. The subjects performed a two-part (A, B) test based on repeated 20-m shuttle runs. Part A comprised 60 m of walking, a maximal 15-m sprint, 60 m of cruising (90% maximal oxygen uptake, V˙O_2max) and 60 m of jogging (45% V˙O_2max) repeated for 75 min with a 3-min rest every 15 min. Part B involved an exercise and rest pattern of 60-s running at 100% V˙O_2max and 60-s rest which was continued until fatigue. Although the GP and EA did not respond differently in terms of distances completed, performance was 25 (SEM 4)% less (main effect trial, P < 0.01) in the hot (HT) compared with the moderate trial (MT). Sprints of 15 m took longer to complete in the heat (main effect, trial, P < 0.01), and sprint performance declined during HT but not MT (interaction, trial × time, P < 0.01). A very high correlation was found between the rate of rise in rectal temperature in HT and the distance completed [GP, r =−0.94, P < 0.01; EA (n = 7), r = −0.93, P < 0.01]. Blood lactate [La⁻ ]_b and plasma ammonia [NH₃]_p1 concentrations were higher for GP than EA, but were similar in HT and MT [La⁻ ]_b, HT: GP vs EA, 8.0 (SEM 0.9) vs 4.9 (SEM 1.1) mmol · l⁻¹; MT: GP vs EA, 8.0 (SEM 1.3) vs 4.4 (SEM 1.2) mmol · l⁻¹; interaction, group × time, P < 0.01; [NH₃]_p1, HT: GP vs EA, 70.1 (SEM 12.7) vs 43.2 (SEM 6.1) mmol · l⁻¹; MT: GP vs EA, 76.8 (SEM 8.8) vs 32.5 (SEM 3.8) μmol · l⁻¹; interaction, group × time, P < 0.01. Ad libitum water consumption was higher in HT [HT: GP vs EA, 18.9 (SEM 2.9) vs 13.5 (SEM 1.7) ml · kg⁻¹ · h⁻¹; MT: GP vs EA, 12.7 (SEM 3.7) vs 8.5 (SEM 1.5) ml · kg⁻¹ · h⁻¹; main effect, group, n.s.; main effect, trial, P < 0.01]. These results would suggest that elevated body temperature is probably the key factor limiting performance of prolonged, intermittent, high-intensity running when the ambient temperature is high, but not because of its effect on the metabolic responses to exercise. Accepted: 19 July 1999