Plasma Concentrations of Immunoreactive Atrial Natriuretic Peptide in Hospitalized Cirrhotic and Noncirrhotic Patients: Evidence for a Role of Deficient Atrial Natriuretic Peptide in Pathogenesis of Cirrhotic Ascites

Atrial natriuretic peptide(s) (ANP), are thought to be released from the cardiac atria in response to distension. If decreased effective circulating blood volume is important in pathogenesis of ascites, plasma ANP levels would be expected to be decreased in ascitic subjects because of decreased atrial distension. To test this hypothesis, we measured plasma ANP by competitive radioimmunoassay in three groups of fasted, supine hospitalized subjects: nine noncirrhotic control subjects, 12 cirrhotics without ascites, and 17 cirrhotics with moderate to marked ascites. Immunoreactive plasma ANP concentrations were 195 +/- 41, 171 +/- 31, and 137 +/- 34 pg/ml (m +/- SD), respectively, in the three groups. The mean concentration in the group with cirrhosis and ascites was significantly (p less than or equal to 0.01) les than those of the other two groups, which did not differ from one another. These results support the concept that decreased effective circulating volume plays a role in pathogenesis of cirrhotic ascites, and that a relative deficiency of ANP plays a role in the sodium retention of decompensated cirrhosis.     

A Randomized Controlled Trial of Intensive Care Management for Disabled Medicaid Beneficiaries with High Health Care Costs

ObjectiveTo evaluate outcomes of a registered nurse–led care management intervention for disabled Medicaid beneficiaries with high health care costs.ConclusionsWe found no health care cost savings for disabled Medicaid beneficiaries randomized to intensive care management. Among participants, care management may have the potential to increase access to needed care, slow growth in the number and therefore cost of unplanned hospitalizations, and prevent homelessness. These findings apply to start-up care management programs targeted at high-cost, high-risk Medicaid populations.     

A holistic approach to chronic pain management that involves all stakeholders: change is needed

Chronic pain affects a large proportion of the population, imposing significant individual distress and a considerable burden on society, yet treatment is not always instituted and/or adequate. Comprehensive multidisciplinary management based on the biopsychosocial model of pain has been shown to be clinically effective and cost-efficient, but is not widely available. A literature review of stakeholder groups revealed many reasons for this, including: i) many patients believe healthcare professionals lack relevant knowledge, and consultations are rushed, ii) general practitioners consider that pain management has a low priority and is under-resourced, iii) pain specialists cite non-adherence to evidence-based treatment, sub-optimal prescribing, and chronic pain not being regarded as a disease in its own right, iv) nurses’, pharmacists’ and physiotherapists’ skills are not fully utilized, and v) psychological therapy is employed infrequently and often too late.

Many of the issues relating to physicians could be addressed by improving medical training, both at undergraduate and postgraduate levels – for example, by making pain medicine a compulsory core subject of the undergraduate medical curriculum. This would improve physician/patient communication, increase the use of standardized pain assessment tools, and allow more patients to participate in treatment decisions. Patient care would also benefit from improved training for other multidisciplinary team members; for example, nurses could provide counseling and follow-up support, psychologists offer coping skills training, and physiotherapists have a greater role in rehabilitation. Equally important measures include the widespread adoption of a patient-centered approach, chronic pain being recognized as a disease in its own right, and the development of universal guidelines for managing chronic non-cancer pain.

Perhaps the greatest barrier to improvement is lack of political will at both national and international level. Some powerful initiatives and collaborations are currently lobbying policy-making bodies to raise standards and reduce unnecessary pain – it is vital they continue.     

MCIP1 overexpression suppresses left ventricular remodeling and sustains cardiac function after myocardial infarction

Pathological remodeling of the left ventricle (LV) after myocardial infarction (MI) is a major cause of heart failure. Although cardiac hypertrophy after increased loading conditions has been recognized as a clinical risk factor for human heart failure, it is unknown whether post-MI hypertrophic remodeling of the myocardium is beneficial for cardiac function over time, nor which regulatory pathways play a crucial role in this process. To address these questions, transgenic (TG) mice engineered to overexpress modulatory calcineurin-interacting protein-1 (MCIP1) in the myocardium were used to achieve cardiac-specific inhibition of calcineurin activation. MCIP1-TG mice and their wild-type (WT) littermates, were subjected to MI and analyzed 4 weeks later. At 4 weeks after MI, calcineurin was activated in the LV of WT mice, which was significantly reduced in MCIP1-TG mice. WT mice displayed a 78% increase in LV mass after MI, which was reduced by 38% in MCIP1-TG mice. Echocardiography indicated marked LV dilation and loss of systolic function in WT-MI mice, whereas TG-MI mice displayed a remarkable preservation of LV geometry and contractility, a pronounced reduction in myofiber hypertrophy, collagen deposition, and beta-MHC expression compared with WT-MI mice. Together, these results reveal a protective role for MCIP1 in the post-MI heart and suggest that calcineurin is a crucial regulator of postinfarction-induced pathological LV remodeling. The improvement in functional, structural, and molecular abnormalities in MCIP1-TG mice challenges the adaptive value of post-MI hypertrophy of the remote myocardium. The full text of this article is available online at http://circres.ahajournals.org.     

Failure of adult marrow-derived stem cells to generate marrow stroma after successful hematopoietic stem cell transplantation

OBJECTIVE: The existence of adult, marrow-derived stem cells that retain the ability to generate various tissues is an appealing concept that has considerable therapeutic potential. The aim of this study was to test the extent of this proposed plasticity by defining the ability of adult marrow and peripheral blood stem cells to generate stromal cells of the marrow microenvironment. PATIENTS AND METHODS: We examined expanded populations of stromal cells from four patients 1 to 27 years after allogeneic, sex-mismatched marrow, or peripheral blood stem cell transplantation. The cultured stromal cells were stained by immunofluorescence and with nonspecific esterase (NSE) to detect macrophages, which can constitute a significant component of a primary long-term marrow culture. Fluorescence in situ hybridization (FISH) probes for chromosomes X and Y were applied to distinguish donor from host cells. RESULTS: FISH analysis of replicate slides indicated a good correlation between the number of NSE(+) cells and the number of donor-derived cells. By applying NSE and FISH to the same cells and capturing both bright-field and epifluorescence images, we confirmed that all donor signals were derived from NSE(+) macrophages. CONCLUSION: After successful allogeneic stem cell transplantation, the marrow stroma remains host in origin, even after 27 years of 100% donor hematopoiesis.     

Associations of Uncertainty With Psychological Health and Quality of Life in Older Adults With Advanced Cancer

ContextOlder adults with advanced cancer face uncertainty related to their disease and treatment.ObjectivesTo evaluate the associations of uncertainty with psychological health and quality of life (QoL) in older adults with advanced cancer.MethodsSecondary cross-sectional analysis of baseline data from a national clustered geriatric assessment trial. Patients 70 years and older with advanced cancer considering a new line of chemotherapy were recruited. We measured uncertainty using the modified nine-item Mishel Uncertainty in Illness Scale. Dependent variables included anxiety (Generalized Anxiety Disorder-7), depression (Generalized Depression Scale-15), distress (distress thermometer), QoL (Functional Assessment of Cancer Therapy—General), and emotional well-being (Functional Assessment of Cancer Therapy—General subscale). We used multivariate linear regression analyses to evaluate the association of uncertainty with each dependent variable. We conducted a partial least squares analysis with a variable importance in projection (VIP) plot to assess the contribution of individual variables to the model. Variables with a VIP <0.8 were considered less influential.ResultsWe included 527 patients (median age 76 years; range 70–96). In multivariate analyses, higher levels of uncertainty were significantly associated with greater anxiety (β = 0.11; SE = 0.04), depression (β = 0.09; SE = 0.02), distress (β = 0.12; SE = 0.02), as well as lower QoL (β = ?1.08; SE = 0.11) and emotional well-being (β = ?0.29; SE = 0.03); the effect sizes were considered small. Uncertainty items related to disease and treatment were most strongly associated with psychological health and QoL scores (all VIP >0.8).ConclusionUncertainty among older patients with advanced cancer is associated with worse psychological health and QoL. Tailored uncertainty management strategies are warranted.     

Critical Re-examination of the Specificity of Auto-anti-Rh Antibodies in Patients with a Positive Direct Antiglobulin Test

Forty-eight autoantibodies with apparent 'simple' anti-Rh specificity (anti-e, -E, -c, -D, -C, -Ce, -G), have been studied by means of multiple absorption tests. The finding that 34 (70.8%) of these antibodies could bind to red blood cells lacking the antigens that the antibodies appeared to define, indicated that the antibodies had different specificities than seemed to be the case in initial antibody identification tests. Those autoantibodies that at first appeared to be directed against the Rh antigens e, E or c, most often had anti-Hr or anti-Hro specificity. These data explain why some apparent anti-Rh autoantibodies can be eluted from the red blood cells of patients negative for the antigens that the antibodi:s appear to define. However, they also illustrate that the phenomenon of autoantibodies mimicking specificities that they do not possess is common in patients positive for the antigens against which their autoantibodies appear to be directed. An explanation for the mode of action of these autoantibodies in complexing with the Rh agglutinogen is proposed, and the significance of the antibodies in transfusion therapy is considered.     

Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women

BACKGROUND: Whether the natural history of human papillomavirus (HPV) infection is affected by bacterial vaginosis (BV) or Trichomonas vaginalis (TV) infection has not been adequately investigated in prospective studies. METHODS: Human immunodeficiency virus 1 (HIV-1)-infected (n=1763) and high-risk HIV-1-uninfected (n=493) women were assessed semiannually for BV (by Nugent's criteria), TV infection (by wet mount), type-specific HPV (by polymerase chain reaction with MY09/MY11/HMB01 HPV primers), and squamous intraepithelial lesions (SIL) (by cytological examination). Sexual history was obtained from patient report at each visit. Risk factors for prevalent and incident HPV infection and SIL were evaluated by use of multivariate models. RESULTS: BV was associated with both prevalent and incident HPV infection but not with duration of HPV infection or incidence of SIL. TV infection was associated with incident HPV infection and with decreased duration and lower prevalence of HPV infection. TV infection had no association with development of SIL. Effects of BV and TV infection were similar in HIV-1-infected and high-risk HIV-1-uninfected women. HIV-1 infection and low CD4(+) lymphocyte count were strongly associated with HPV infection and development of SIL. CONCLUSIONS: BV and TV infection may increase the risk of acquisition (or reactivation) of HPV infection, as is consistent with hypotheses that the local cervicovaginal milieu plays a role in susceptibility to HPV infection. The finding that BV did not affect persistence of HPV infection and that TV infection may shorten the duration of HPV infection helps explain the lack of effect that BV and TV infection have on development of SIL.