Current Medicine News Results

Postmenopausal hormone therapy and coronary artery atherosclerosis.

Climacteric. 2012 Feb; 15(1): 96-7
Pines A

Improving the management of dyspnea in the community using rapid learning approaches.

Chron Respir Dis. 2012; 9(1): 51-61
Kamal AH, Miriovsky BJ, Currow DC, Abernethy AP

Patients with chronic pulmonary disease often suffer from breathlessness or dyspnea. Traditional evidence generation techniques to expand upon current treatment paradigms are limited by the significant delay between study initiation and clinical implementation of findings. Rapid learning health care is a novel approach to health care delivery that relies on intelligent and continuous integration of clinical and research data sets to deliver personalized medicine using the most current evidence available. Results of important studies in the management of chronic respiratory disease are presented in brief; however, the focus of this review is on evidence supporting the implementation of a rapid learning model for symptom management. Recent findings suggest that a rapid learning system is feasible and acceptable to patients with advanced illness, helps monitor symptoms overtime, facilitates study of the impact of novel interventions, and can identify unrecognized needs and concerns. A rapid learning model improves comprehensive assessment, timeliness of intervention, and accrual of contemporaneous data to support best practice that tailors care specific to the needs of patients as their disease and lifestyle change overtime. Using the rapid learning health care model, data collected in the process of routine care can simultaneously function both as clinical information and as a resource for research on patient-centered experiences and outcomes.

Self-management programmes for COPD: Moving forward.

Chron Respir Dis. 2012; 9(1): 27-35
Effing TW, Bourbeau J, Vercoulen J, Apter AJ, Coultas D, Meek P, Valk P, Partridge MR, Palen J

Self-management is of increasing importance in chronic obstructive pulmonary disease (COPD) management. However, there is confusion over what processes are involved, how the value of self-management should be determined, and about the research priorities. To gain more insight into and agreement about the content of programmes, outcomes, and future directions of COPD self-management, a group of interested researchers and physicians, all of whom had previously published on this subject and who had previously collaborated on other projects, convened a workshop. This article summarises their initial findings. Self-management programmes aim at structural behaviour change to sustain treatment effects after programmes have been completed. The programmes should include techniques aimed at behavioural change, be tailored individually, take the patient's perspective into account, and may vary with the course of the patient's disease and co-morbidities. Assessment should include process variables. This report is a step towards greater conformity in the field of self-management. To enhance clarity regarding effectiveness, future studies should clearly describe their intervention, be properly designed and powered, and include outcomes that focus more on the acquisition and practice of new skills. In this way more evidence and a better comprehension on self-management programmes will be obtained, and more specific formulation of guidelines on self-management made possible.

Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis.

Chron Respir Dis. 2012; 9(1): 9-16
Sequeiros IM, Jarad N

Time until the subsequent exacerbation (PEx) in cystic fibrosis (CF) is a significant health outcome and one of the significant end points in clinical trials. Risk factors associated with shorter time until the next exacerbation (TUNE) have not been reported. This is a prospective study. TUNE was the number of days from the end of intravenous (IV) antibiotic treatment of a PEx until the day of start of IV antibiotics for the following PEx. Factors assessed were age, gender, site of treatment, CF-related diabetes (CFRD), allergic bronchopulmonary aspergillosis (ABPA) and infection with Pseudomonas aeruginosa (PA). In addition, we examined parameters obtained at day 14 of treatment including forced expiratory volume in the first second (FEV1), body mass index, CF respiratory symptom score, C-reactive protein (CRP) and serum cytokines. A total of 170 exacerbations in 58 adult CF patients (27 female), mean (SD) age 25.8 (6.7) years were analysed. When analysing individual variables, patients with lower FEV1, greater symptom score and higher CRP at the end of exacerbation were associated with shorter TUNE. Patients with ABPA and CFRD had a shorter TUNE than those without. When applying multiple regression analysis, factors associated with shorter TUNE were older age and lower day-14 FEV1 values. Shorter periods until the following PEx are expected in older CF patients and those with lower FEV1 at the end of course of treatment. When these risk factors are present, there may be a justification to take therapeutic steps to increase the time until the following PEx.

Unravelling self-management for COPD: What next?

Chron Respir Dis. 2012; 9(1): 5-7
Wagg K

One step beyond, does rehabilitation influence physical activity?

Chron Respir Dis. 2012; 9(1): 3-4
Singh S, Morgan M

Addressing the Sluggish Progress in Reducing Maternal Mortality in India.

Asia Pac J Public Health. 2012 Feb 2;
Rai RK, Tulchinsky TH

Although some progress has been made in India, achievement of the Fifth Millennium Development Goal (MDG5; ie, 75% reduction in maternal mortality ratio [MMR] from 1990 by 2015) target seems to be unattainable by 2015. Failure of the National Population Policy, 2000, and the National Health Policy, 2002, to reduce the MMR demanded a new direction, leading to the establishment of a National Rural Health Mission in 2005. This commentary addresses both the real achievements and the hurdles faced in India's stagnating progress in maternal health. Promotion of maternal nutrition and health education, with greater attention to emergency obstetrical care at the district subcenter and primary health care center levels, must be prioritized. These changes of focus are vital to make prenatal, delivery, and postnatal care safer with increased resources allotted to adolescents, the poor, and women living in rural areas in order to enhance maternal health and achieve the MDG target.

Evidence for a genetic role in varicose veins and chronic venous insufficiency.

Phlebology. 2012 Feb 3;
Krysa J, Jones GT, van Rij AM

There is a strong body of circumstantial evidence which implicates genetics in the aetiology and pathology of varicose veins and venous ulcer disease. The aim of this review is to consider the current knowledge of the genetic associations and the ways in which new genetic technologies may be applied to advancing our understanding of the cause and progression of these venous diseases. A number of publications have used a candidate gene approach to identify genes implicated in venous disease. Although these studies have opened up important new insights, there has been a general failure to replicate results in an independent cohort of patients. With our limited knowledge of the biological pathways involved in the pathogenesis of venous disease we are not in a strong position to formulate truly erudite a priori candidate gene hypothesis-directed studies. A genome-wide association study should therefore be considered to help further our understanding of the genetic basis of venous disease. Due to the large sample sizes required for discovery and validation, using the new generations of molecular technologies, it will be necessary to form collaborating groups in order to successfully advance the field of venous disease genetics.

Anatomical and pathological findings in hearts from fetuses and infants with cardiac manifestations of neonatal lupus.

Rheumatology (Oxford). 2012 Feb 3;
Llanos C, Friedman DM, Saxena A, Izmirly PM, Tseng CE, Dische R, Abellar RG, Halushka M, Clancy RM, Buyon JP

Objective. The autopsy and clinical information on children dying with anti-SSA/Ro-associated cardiac manifestations of neonatal lupus (cardiac NL) were examined to identify patterns of disease, gain insight into pathogenesis and enhance the search for biomarkers and preventive therapies.Methods. A retrospective analysis evaluating reports from 18 autopsies of cardiac NL cases and clinical data from the Research Registry for Neonatal Lupus was performed.Results. Of the 18 cases with autopsies, 15 had advanced heart block, including 3 who died in the second trimester, 9 in the third trimester and 3 post-natally. Three others died of cardiomyopathy without advanced block, including two dying pre-natally and one after birth. Pathological findings included fibrosis/calcification of the atrioventricular (AV) node, sinoatrial (SA) node and bundle of His, endocardial fibroelastosis (EFE), papillary muscle fibrosis, valvular disease, calcification of the atrial septum and mononuclear pancarditis. There was no association of pathology with the timing of death except that in the third-trimester deaths more valvular disease and/or extensive conduction system abnormalities were observed. Clinical rhythm did not always correlate with pathology of the conduction system, and the pre-mortem echocardiograms did not consistently detect the extent of pathology.Conclusion. Fibrosis of the AV node/distal conduction system is the most characteristic histopathological finding. Fibrosis of the SA node and bundle of His, EFE and valve damage are also part of the anti-Ro spectrum of injury. Discordance between echocardiograms and pathology findings should prompt the search for more sensitive methods to accurately study the phenotype of antibody damage.

Article summaries for february/march 2012 psychosomatic medicine, vol. 74, issue 2.

Psychosom Med. 2012 Feb; 74(2): 117

A Nogo signal coordinates the perfect match between myelin and axons.

Proc Natl Acad Sci U S A. 2012 Jan 24; 109(4): 1003-4
Scholze AR, Barres BA

Reorienting our view of particle-based adjuvants for subunit vaccines.

Proc Natl Acad Sci U S A. 2012 Jan 24; 109(4): 999-1000
Little SR

Setting up a lung cancer screening program.

J Natl Compr Canc Netw. 2012 Feb 1; 10(2): 277-85
Arenberg D, Kazerooni EA

This article summarizes what is known about the best practices of lung cancer screening and provides suggestions for the proper structure for institutions considering offering lung cancer screening services. Important points of emphasis include the need to confine screening to patients at highest risk, the presence of multidisciplinary teams capable of managing the high number of false-positive findings, the need for additional research on biomarkers and risk models for lung cancer, and the currently unknown cost-effectiveness of lung cancer screening on a societal level.

Treatment of non-small cell lung cancer in the older patient.

J Natl Compr Canc Netw. 2012 Feb 1; 10(2): 230-9
Ganti AK, Deshazo M, Weir AB, Hurria A

Lung cancer is a disease of the elderly, with a median age at diagnosis of 70 years. However, there is a dearth of good quality evidence to guide treatment in this population and most of the data are extrapolated from younger patients. Current research is directed toward establishing simplified instruments to quantify fitness of older patients for various forms of therapy. Although current evidence suggests that outcomes after standard therapy are similar to those seen in younger patients, older patients have an increased incidence of adverse events. Until better predictive markers are available to guide treatment, therapy should be individualized using available instruments, including a comprehensive geriatric assessment. If an older patient is deemed to be fit, it is reasonable to use the treatment options recommended for younger individuals. This article summarizes the available data on the treatment of non-small cell lung cancer in the older patient.

Communicating About Chemotherapy-Induced Nausea and Vomiting: A Comparison of Patient and Provider Perspectives.

J Natl Compr Canc Netw. 2012 Feb 1; 10(2): 149-157
Salsman JM, Grunberg SM, Beaumont JL, Rogers M, Paul D, Clayman ML, Cella D

Despite recent progress, chemotherapy-induced nausea and vomiting (CINV), especially delayed CINV, continues to be a problem. Delayed CINV is underestimated and perceived differently by providers and patients. Communication between providers and patients about this side effect may help improve outcomes. This study identifies patients' and providers' perceptions of management and barriers to quality CINV care. Provider and patient versions of a Nausea and Vomiting Management Barriers Questionnaire were developed to address potential barriers. Providers and patients were given opportunities to add detail in open-ended questions. Providers were recruited through the NCCN and the Oncology Nursing Society mailing lists. Patients who received at least 2 cycles of chemotherapy and experienced CINV were recruited through a consortium of advocacy groups. Both providers (n = 141) and patients (n = 299) completed the survey. Providers (41%) and patients (42%) agreed medication side effects were a concern, but more patients (63%) than providers (36%) tried to limit the number of medications taken (P < .0001). Many providers (67%) spontaneously reported barriers to managing CINV, with financial and patient-related factors among the most common. Few patients (10%) reported cost as a barrier, but 37% endorsed the desire "to be strong by not complaining." Barriers to communication and quality care of CINV differ between caregivers and patients. Addressing misconceptions and establishing mutually consistent goals will lead to more effective overall care.

Diagnostic and treatment considerations when newly diagnosed breast cancer coincides with pregnancy: a case report and review of literature.

J Natl Compr Canc Netw. 2012 Feb 1; 10(2): 145-8
Nye L, Huyck TK, Gradishar WJ

Breast cancer is the most common malignancy associated with pregnancy and is a rare but well-recognized complication. It is hypothesized that as more women continue to delay childbearing, the incidence of breast cancer in pregnancy will increase. Because of the lack of clinical experience with breast cancer in the setting of pregnancy, given its relative infrequency, many patients and physicians believe the diagnosis puts the life of the mother at odds with that of the fetus, but available data suggest that termination of the pregnancy does not improve the outcome for pregnant women with breast cancer. Often diagnosis is delayed because neither patient nor physician suspects malignancy. This report presents a recent case of a young primigravid woman with a newly appreciated breast mass seen at Northwestern University Feinberg School of Medicine as a means of discussing diagnostic considerations, therapeutic options, and supportive care available to the practitioner when managing a pregnant patient with breast cancer.

Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic β cells.

Proc Natl Acad Sci U S A. 2012 Jan 30;
Tang G, Wang Y, Park S, Bajpayee NS, Vi D, Nagaoka Y, Birnbaumer L, Jiang M

The neuropeptide galanin regulates numerous physiological activities in the body, including feeding and metabolism, learning and memory, nociception and spinal reflexes, and anxiety and related behaviors. Modulation of blood glucose levels by suppressing insulin release was the first reported activity for galanin. This inhibition was mediated by one or more pertussis toxin-sensitive G proteins of the G(i/o) subfamily. However, the molecular identities of the specific G protein(s) and intracellular effectors have not been fully revealed. Recently, we demonstrated that mice lacking G(o)2, but not other members of the G(i/o) protein family, secrete more insulin than controls upon glucose challenge, indicating that G(o)2 is a major transducer for the inhibitory regulation of insulin secretion. In this study, we investigated galanin signaling mechanisms in β cells using cell biological and electrophysiological approaches. We found that islets lacking G(o)2, but not other G(i/o) proteins, lose the inhibitory effect of galanin on insulin release. Potentiation of ATP-sensitive potassium (K(ATP)) and inhibition of calcium currents by galanin were disrupted by anti-G(o)2α antibodies. Galanin actions on K(ATP) and calcium currents were completely lost in G(o)2(-/-) β cells. Furthermore, the hyperglycemic effect of galanin is also blunted in G(o)2(-/-) mice. Our results demonstrate that G(o)2 mediates the inhibition of insulin release by galanin by regulating both K(ATP) and Ca(2+) channels in mice. Our findings provide insight into galanin's action in glucose homeostasis. The results may also be relevant to the understanding of galanin signaling in other biological systems, especially the central nervous system.

Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses.

Proc Natl Acad Sci U S A. 2012 Jan 30;
Pica N, Hai R, Krammer F, Wang TT, Maamary J, Eggink D, Tan GS, Krause JC, Moran T, Stein CR, Banach D, Wrammert J, Belshe RB, García-Sastre A, Palese P

After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.

Tcl1 protein functions as an inhibitor of de novo DNA methylation in B-cell chronic lymphocytic leukemia (CLL).

Proc Natl Acad Sci U S A. 2012 Jan 30;
Palamarchuk A, Yan PS, Zanesi N, Wang L, Rodrigues B, Murphy M, Balatti V, Bottoni A, Nazaryan N, Alder H, Rassenti L, Kipps TJ, Freitas M, Croce CM, Pekarsky Y

B-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene (TCL1) in mouse B cells causes a CD5(+) leukemia similar to aggressive human CLL. To examine the mechanisms by which Tcl1 protein exerts its oncogenic activity in B cells, we performed proteomics experiments to identify its interacting partners. We found that Tcl1 physically interacts with de novo DNA methylthansferases Dnmt3A and Dnmt3B. We further investigated the effects of Tcl1 up-regulation on the enzymatic activity of Dnmt3A and found that Tcl1 overexpression drastically inhibits Dnmt3A function. In addition, B cells from TCL1 transgenic mice showed a significant decrease in DNA methylation compared with WT controls. Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis.

Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses.

Proc Natl Acad Sci U S A. 2012 Jan 30;
Lou X, Fan F, Messa M, Raimondi A, Wu Y, Looger LL, Ferguson SM, De Camilli P

Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.