Atrial natriuretic peptide levels in the prediction of congestive heart failure risk in frail elderly.

OBJECTIVE--To develop a noninvasive clinical predictive model for acute congestive heart failure (CHF) in a frail elderly cohort using bedside clinical assessment (medical history and physical examination) and venous atrial natriuretic peptide (ANP) levels. DESIGN--One-year prospective blinded cohort study. SETTING--Life care facility. PARTICIPANTS--Three hundred thirty-one frail, elderly volunteers free of acute illness at study entry (mean +/- SD age, 88 +/- 7 years; 23% male, 77% female). MAIN OUTCOME MEASURE--Clinical episodes of CHF with confirmation of acute pulmonary edema by chest roentgenogram. RESULTS--Fifteen percent of the elderly cohort developed at least one episode of CHF during the 1-year follow-up period. Those developing CHF had significantly higher mean +/- SE ANP values at study entry: 493 +/- 55 vs 207 +/- 15 pmol/L. The risk for development of CHF rose progressively with increasing ANP levels at study entry. In multivariate analysis, only two independent variables significantly predicted CHF: ANP value greater than 200 pmol/L (adjusted odds ratio [OR], 7.9; 95% confidence interval [CI], 3.2 to 19.2) and history of CHF in the previous year (adjusted OR, 7.0; 95% CI, 2.9 to 17). Stratifying the cohort by these two variables results in three CHF risk groups: 55% of the population at 3% annual risk of CHF, 37% of the population at 20% to 24% annual risk of CHF, and 8% of the population at 66% annual risk of CHF. CONCLUSIONS--This simple clinical prediction model identifies elderly subjects at risk for CHF and allows appropriate focusing of medical resources for prevention, early detection, and treatment of this highly morbid clinical syndrome.     

Motivation and Maternal Presence during Induction of Anesthesia

Background: The authors developed a measure to determine whether maternal motivation to be present during induction (Motivation for Parental Presence during Induction of Anesthesia [MPPIA]) is related to children's anxiety during the induction process.

Methods: Mothers and children (aged 2-12 yr) undergoing outpatient, elective surgery and general anesthesia were enrolled in this study (n = 289 dyads). Items to assess motivation for parental presence during induction were selected by experts in anesthesiology, psychology, and child development; mothers completed the resulting 14-item measure as well as assessments of anxiety and coping style. Children's anxiety and compliance was assessed during induction of anesthesia. Factor analysis was performed, and maternal motivation was then examined against children's anxiety during induction of anesthesia.

Results: Factor analysis resulted in four scales with a total variance of 72.3%: MPPIA-Desire, MPPIA-Hesitancy, MPPIA-Anxiety, and MPPIA-Preparation. Analysis supported the reliability (0.89-0.94) and validity of the MPPIA. The authors found that mothers with high MPPIA-Desire and low MPPIA-Hesitancy had children with significantly higher anxiety (P < 0.0001) during induction of anesthesia, as compared with mothers with low MPPIA-Desire and MPPIA-Hesitancy. The authors also found that highly motivated mothers reported significantly higher levels of anxiety (P = 0.007).     

TRACP Influences Th1 pathways by affecting dendritic cell function.

TRACP, a marker of osteoclasts, is also expressed by cells of the immune system. We identified a novel function for TRACP in the dendritic cell. DCs from TRACP knockout mice have impaired maturation and trigger reduced Th1 responses in vivo. We postulate that TRACP has an important role in the presentation of antigens to T cells. INTRODUCTION: TRACP is highly expressed by osteoclasts, activated macrophages, and dendritic cells (DCs). Knockout mice lacking TRACP have an intrinsic defect in osteoclastic resorption and macrophages that display abnormal immunomodulatory responses and cytokine secretion profiles. Our aim in this study was to investigate the significance of TRACP in the inductive phase of the immune response by examining dendritic cells from TRACP(-/-) mice. MATERIALS AND METHODS: Maturational state and function of leukocyte subsets in mice was assessed by flow cytometry. The ability of the immune system to respond to nonspecific activation and to specific antigen was assessed by delayed type hypersensitivity and the presence of isotype-specific serum antibody in vivo and T-cell proliferation and cytokine production in vitro. RESULTS: The ability of lipopolysaccharide (LPS) to upregulate MHC II and CD80 in DCs from TRACP(-/-) mice was reduced compared with wildtype mice, although production of IL-10 by DCs from TRACP-deficient animals was increased. T- and B-cell responses not involving antigen presentation (anti-CD3, TNP-ficoll) were normal in TRACP(-/-) mice, but responses to T-dependent antigens were impaired. Specifically, TRACP(-/-) mice had defective delayed hypersensitivity responses to picryl chloride and reduced proliferative responses to ovalbumin compared with wildtype mice. In response to ovalbumin, but not anti-CD3, T cells from TRACP(-/-) mice produced less interferon-gamma (IFN-gamma), but there was no difference in IL-4 production: TRACP(-/-) mice also produced less ovalbumin (OVA)-specific IgG2a after immunization. CONCLUSIONS: The finding that DCs from TRACP(-/-) mice have impaired maturation and defective Th1 responses shows that TRACP is important for polarizing responses in na?ve T cells to antigen-presented dendritic cells.     

The Sachs report: investing in health for economic development--or increasing the size of the crumbs from the rich man's table? Part II.

The Commission on Macroeconomics and Health report (Sachs report of 2001) has been heralded as inspiring and groundbreaking and is being adopted as the blueprint for global health policymaking. This article argues that the report is deeply conservative and unoriginal. It encourages medico-technical solutions to public health problems; it ignores macroeconomic determinants and other root causes of both poor health and poverty; it reverses public health logic and history; it is based on a set of flawed assumptions; it reflects one particular economic perspective to the exclusion of all others; and it recommends greater amounts of charity while preserving the status quo of a deeply unjust and irrational international economic order. Wishful thinking and ideology are presented as established facts to legitimize globalization, and health is conceived primarily as an input to productivity rather than as a human right. The benefits that would result from simple, macroeconomic measures directed toward social justice and the meeting of basic needs are incomparably greater than those that would result from following CMH recommendations in terms of sustainable improvements in both health and economic well-being. The ultimate source of poor health status and miserable living conditions is the extreme concentration of power, nationally and internationally, in the hands of the few.     

Effect of 6-hydroxydopamine lesions of the amygdala on intravenous cocaine self-administration under a progressive ratio schedule of reinforcement

Bilateral six-hydroxydopamine (6-OHDA) lesions were placed in the amygdala of rats self-administering cocaine (1.5 mg/kg per injection i.v.) under a progressive ratio schedule of reinforcement. Post-lesion access to three doses of cocaine (1.5, 0.75 and 0.37 mg/kg per injection i.v.) revealed a lesion effect only at the highest dose. At this dose, the lesion caused a significant increase in breaking point. No change in the breaking point was produced at the lower two doses. The biochemical results show a significant reduction in dopamine and DOPAC levels within the amygdala and an increase in dopamine within the NACC. In contrast, noradrenaline and serotonin (5-HT) levels were unaffected by the lesion in any of the dissected areas. These results demonstrate that no specific effect on cocaine reinforcement was produced by 6-OHDA lesions of the amygdala. The possibility that the lesion may have attenuated the anxiogenic qualities of the high dose of cocaine is discussed.     

Development of Resistance During Antimicrobial Therapy: A Review of Antibiotic Classes and Patient Characteristics in 173 Studies

The incidence of emergent resistance and clinical factors affecting its development were evaluated by retrospective review of 173 studies encompassing over 14,000 patients. Eight antibiotic classes and 225 individual treatment regimens were evaluated. Emergent resistance occurred among 4.0% of all organisms and 5.6% of all infections treated. It appeared to be significantly more frequent with penicillin and aminoglycoside monotherapy, with significantly lower rates associated with imipenem-cilastatin, aztreonam, and combination therapy. Clinical failure also appeared to be significantly more likely to occur after emergence of resistance among organisms treated with fluoroquinolones or aminoglycosides. Infections associated with higher resistance rates were cystic fibrosis, osteomyelitis, and lower respiratory tract infections. Resistance was most common in patients in intensive care units or receiving mechanical ventilation. It was also significantly frequent among studies performed in university or teaching hospitals. Organisms associated with high resistance rates were Pseudomonas aeruginosa, Serratia, Enterobacter, and Acinetobacter sp. Factors such as infection type, underlying diseases, type of institution, and specific pathogens warrant consideration when examining emergent resistance.     

Variable Disposition of Ciprofloxacin in Critically Ill Patients Undergoing Continuous Arteriovenous Hemodiafiltration

Continuous arteriovenous hemodiafiltration (CAVHD) is being used increasingly in critically ill patients with acute renal failure (ARF). We prospectively evaluated extracorporeal and total systemic clearances (Cl_CAVHD and Cl_s) of ciprofloxacin during CAVHD in four patients with severe ARF to assess the adequacy of drug dosing. Ciprofloxacin serum and ultrafiltrate concentrations were measured by high-performance liquid chromatography. The Cl_CAVHD accounted for approximately 5.9% (range 2.8–11.6%) of Cl_s of ciprofloxacin. However, large variability in serum concentrations was observed with the normally recommended dose of 400 mg/day, and doses of up to 800 mg/day were required to maintain concentrations suitable for treatment of serious infections. High daily doses of ciprofloxacin required in these patients are likely related to altered pharmacokinetics in serious illness as well as to the increased extracorporeal clearance during CAVHD. Clinical studies to define appropriate dosing recommendations for ciprofloxacin during CAVHD are necessary to guide clinicians in optimum drug use.