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PubMed2006

[The molecular biology of aging--therapeutic interventions?].

Aging is a complex mechanism of progressive and irreversible processes occurring to molecules, to cells and to the whole organism and ending with death. Genetic - so called "programmed" - factors and the combination of environmental interactions play the most important role in its development. Changes in macromolecules caused by free radicals, non-enzymatic glycosylation and apoptosis have a special role in the pathomechanism of aging. Endocrine and immune systems have also an important influence and control on the process. Those environmental effects, as for example irradiation, toxic chemicals, metal ions, free radicals play a determinant role in the development of aging. Diseases of old age should be distinguished from aging per se, although changes in old age increase the frequency of diseases. Those aging changes, which are associated with a generalized increase in mortality (but not with specific disease) would qualify as biomarkers of aging and would distinguish biological age from chronological age (passage of time). Because of increased average lifetime of people in the "western world", basic and clinical research in connection with aging and geriatrics has special importance in medicine. Better understanding of molecular and cellular mechanisms of aging could improve not only medical care of the elderly but could hold out also some hope in finding feasible solutions to slow down the aging process as well.

Aging↗

PubMed2000

Can addressing family relationships improve outcomes in chronic disease? Report of the National Working Group on Family-Based Interventions in Chronic Disease.

The management of patients with chronic disease constitutes the largest single cost to the health care system in the United States. New approaches and methods are needed to reduce preventable complications and to enhance the health and well-being of patients with chronic disease and their families. Interventions that target the family setting in which disease management takes place have emerged as an alternative to traditional strategies that focus only on the individual patient or that consider the family only as a peripheral source of positive or negative social support. In this approach, the educational, relational, and personal needs of all family members are emphasized. Data reviewed by the National Working Group on Family-Based Interventions in Chronic Disease identified potential mechanisms by which the relational context of the family affects disease management and how characteristics of family relationships serve as risk or protective factors. In this paper we describe the major forms of family-based interventions, review the results of selected clinical trials, and present applications for clinical practice. The data suggest that approaches to the management of chronic disease should be expanded to include the broader relational context in which disease management takes place. Although it adds complexity to clinical intervention, this approach increases clinical flexibility, addresses the important players in disease management, and accounts for a significant number of risk and protective factors that affect outcome.

Adolescent↗

PubMedDate not supplied

Reperfusion treatment of ST-elevation acute myocardial infarction.

Reperfusion treatment of ST-segment elevation myocardial infarction (STEMI) is one of the medical interventions with the largest potential for saving human lives, independently of age and gender. An attempt to reopen an acutely occluded coronary artery can be done within a wide array of possibilities, from the simple administration of aspirin to the combination of drugs and complex coronary artery interventions. Fibrinolytic drugs and aspirin represent the easiest way to attempt reperfusion and together offer an acceptable compromise between opportunity for treatment and efficacy. Other drugs and the use of invasive revascularization alternatives yield further advantages, and in some high-risk subgroups may be the most rational treatment approach. Beyond investigator's bias and dedication to either form of reperfusion treatment, interventions and/or drugs should be used as needed (and as possible) to increase the overall impact of reperfusion treatment in the community, taking advantage of the best potential of each approach. Most resources have been directed toward the improvement of reperfusion rates with the combination of fibrinolytic and antiplatelet drugs or with angioplasty. These efforts have certainly raised costs, but have not decisively improved clinical outcome nor have they broadened the impact of reperfusion treatment in the community. Indeed, the main shortcoming of reperfusion therapy is that the cohort of untreated patients is still larger than the cohort of treated patients. At a time when mortality of patients with STEMI reaching the hospital and receiving treatment has decreased significantly, the prehospital diagnosis and treatment of STEMI with the objective of enlarging the treated population and shortening the pretreatment delays is likely the best strategy to further reduce mortality. The need for a population approach to treatment of STEMI is even more obvious when considering the expanding patient load that continuously worsens its clinical risk profile, together with the increasing incidence of diabetes, obesity, hypertension, and smoking habits. The target for improving reperfusion treatment of STEMI in the future, and thereby saving more lives, seems now to involve a cultural change and fulfillment of an organizational mission more than an incremental improvement in the current pharmacologic or interventional approach. These epidemiologic and social aspects of contemporary medicine deserve full attention at a time when researchers, clinicians, and health care providers tend to focus primarily on technological advances.

Abciximab↗

PubMedDate not supplied

The macro-ethics of genomics to health: the physiome project.

Advances in pharmacology and genomics, and their intervention in human biology are beyond our abilities to understand their consequences. Therapeutic intervention in highly complex, non-linear, adaptive biological systems results in some unforeseen and undesirable consequences. To do the most good with the least harm, the information on biological systems should be gathered into databases, and into comprehensive quantitative models that can help to predict the long-range effects of proposed interventions. This is a societal or professional macro-ethical imperative. The Physiome Project helps to meet this imperative via databasing and creating models and tools for large-scale integration.

Computational Biology↗

PubMed1993

Diarrhoeal disease: current concepts and future challenges. Water, sanitation and diarrhoea: the limits of understanding.

This paper reviews the application of epidemiological understanding of diarrhoeal disease to interventions in water and sanitation. Over the past 20 years, great efforts have been made to elucidate the relationships between water supply, sanitation and diarrhoeal disease. At the outset, it was hoped that improved understanding of these relations could provide a rational framework for the planning of public health engineering interventions. This paper also reviews historical and recent perceptions of water, sanitation, and diarrhoeal disease, and summarizes progress to date. On the one hand, some fundamental ideas about the relative importance of water quality and quantity in the transmission of diarrhoeal disease have changed, and there is increased recognition of the complex interrelationships between interventions, hygiene behaviour and health. On the other hand, our understanding of the impact of interventions is painfully incomplete, and is unlikely to improve dramatically in the near future. While further research can usefully illustrate a variety of interactions in specific contexts, globally applicable planning guidelines and design criteria appear a dangerous will-o'-the-wisp. While we know more than ever before about water, sanitation and diarrhoea, much remains unknown, and is perhaps unknowable.

Child↗

PubMed2000

Clinical outcomes following "rescue" administration of abciximab in patients undergoing percutaneous coronary angioplasty.

Pre-intervention administration of abciximab in patients at "high risk" for coronary angioplasty has been shown to reduce acute and long-term cardiac outcomes. The role of intra-procedural ("rescue") administration of abciximab has not been fully elucidated. We assessed the clinical outcomes associated with rescue administration of abciximab during complex percutaneous coronary interventions. We studied in-hospital and long-term (1-year) outcomes (death, myocardial infarction and target lesion revascularization) of 298 consecutive patients (78% male; age, 62 +/- 11 years; 83% with acute coronary syndrome) treated with abciximab for thrombus-containing lesions, sub-optimal angioplasty results, procedural dissections or other complications. Stents were used in 73% of procedures. Procedural success was 97.0% and overall major in-hospital complication rate was 3.0% (death, 1.3%; Q-wave myocardial infarction, 0.7%; and emergent bypass surgery, 1.0%). Most frequent angiographic complications included visible thrombus (17%), dissections (17%), threatened closure (7%), and distal embolization (7%). In-hospital non-Q wave myocardial infarction (defined as CK-MB 5 times normal) occurred in 31.0%. Out-of-hospital to one-year events included death (1.7%), Q-wave myocardial infarction (2.7%), and target lesion revascularization (15.1%); cardiac event-free survival was 82.9%. We conclude that rescue administration of abciximab is associated with relatively low in-hospital complications and favorable long-term outcome in patients with sub-optimal angioplasty results and/or procedure-related complications, although peri-procedural non-Q wave myocardial infarction rate is high. A clinical and cost-effective comparison between provisional and rescue administration of abciximab may be warranted.

Abciximab↗

PubMed2004

A case of complex regional pain syndrome type II after transradial coronary intervention.

The transradial approach for coronary catheterization is now a routine technique without serious complications at the puncture site. We report a case of complex regional pain syndrome type II (CRPS type II) in the hand after the transradial coronary intervention, which may alert medical personnel that the technique may cause serious regional pain with disability. A 61-year-old woman underwent coronary intervention via the right radial artery for the treatment of unstable angina. After the operation she complained of severe pain in the right hand, consistently felt along the median nerve distribution. The nerve conduction study suggested carpal tunnel syndrome. We made a diagnosis of CRPS type II, and the patient received stellate ganglion blockade, cervical epidural blockade, and administration of amitriptyline and loxoprofen. The symptoms gradually improved and her activities of daily living markedly improved. The median nerve appeared to be damaged by local compression and potential ischemia. Careful attention should be paid to avoid CRPS type II, associated with excess compression.

Cardiac Catheterization↗

PubMed2004

Optimal therapeutic approaches to femoropopliteal artery intervention.

Superficial femoral artery disease presents a complex challenge for therapy. The extent of vascular involvement may vary from focal disease with symptoms of intermittent claudication to long total occlusions manifest as critical limb ischemia. Optimal therapy requires understanding the available options including exercise programs, pharmacologic medical therapy, surgery and interventional endovascular therapy. Rapidly advancing endovascular technology for enabling safe intervention in complex, long occlusive segments of the superficial femoral artery continues to emerge. New devices like the SafeCross wire, Excimer laser, Silverhawk Atherectomy catheter, Cryoplasty catheter and new generations of bare metal and drug-eluting nitinol stents are shifting the paradigm for therapy from surgical to more endovascular treatment even for the most complex disease presentation.

Arterial Occlusive Diseases↗

PubMed2000

Interventions to promote collaboration between nurses and doctors.

BACKGROUND: Lack of nurse-doctor collaboration contributes to problems in quality and efficiency of patient care. OBJECTIVES: To assess the effects of interventions designed to improve nurse-doctor collaboration. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register and database of studies awaiting assessment, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, the Database of Abstracts of Reviews of Effectiveness, MEDLINE, and reference lists of articles up to the end of October 1999. SELECTION CRITERIA: Randomised trials, controlled before-and-after studies and interrupted time series of interventions to improve collaboration between nursing and medical professionals sharing patient care in primary or hospital care settings. DATA COLLECTION AND ANALYSIS: One reviewer assessed the eligibility of potentially relevant studies, extracted data and assessed the quality of included studies; a second reviewer undertook duplicate assessments on the eligibility of some articles and data abstraction on all included studies. MAIN RESULTS: Two trials involving 1945 people were included. One six month trial involving 1102 admissions evaluated daily, structured, team ward rounds, in which nurses, doctors and other professionals made care decisions jointly. There was shortened average length of hospital stay (LOS) from 6.06 to 5.46 days, and reduced hospital charges from US$ 8090 to 6681. There were no differences in mortality rates or the type of care to which patients were discharged. Another three month trial involving 843 admissions compared two female wards and evaluated a four times per week round. There were no significant differences between the intervention and control wards in total average length of stay for all patients (11.7 days in intervention ward versus 11.6 in the control ward). Excluding patients who died in hospital revealed shortened length of stay in the intervention ward (intervention ward 10.5 days, control ward 11.9). Mortality rates were not significantly different. REVIEWER'S CONCLUSIONS: Increasing collaboration improved outcomes of importance to patients and to health care managers. These gains were moderate and affected health care processes rather than outcomes. Further research is needed to confirm these findings. The logistic challenge presented by the complexity of the interventions and the need for large sample sizes due to the likely modest impact and rarity of outcome events may best be met by multi-centre studies. Before launching such studies qualitative research is needed to identify barriers to collaboration. Interventions other than nurse-doctor ward rounds and team meetings should also be tested.

Cooperative Behavior↗

PubMed2002

Aggressive and neutral interventions in conflicts in captive groups of brown lemurs (Eulemur fulvus fulvus).

Third-party interventions in conflicts have revealed complexity in primate social relationships. This type of intervention has seldom been analyzed in prosimians, although many of these species exhibit complex (multimale/multifemale) social organizations. The present study on captive brown lemurs (Eulemur fulvus fulvus) shows that dominant individuals were more likely to intervene in conflicts. Both males and females intervened aggressively in conflicts. Female aggressive interventions occurred mainly on behalf of close kin, whereas males mainly intervened on behalf of juveniles. This study also provides the first record of neutral or peaceful interventions in lemurs. Although females intervened neutrally, almost all neutral interventions were by dominant males. Dominant males intervened in conflicts neutrally more often than aggressively, principally in conflicts between adults and juveniles or between juveniles. Neutral interventions by males always ended the conflicts and were often followed by affiliative contacts between participants (intervenors and opponents). In lemurs, female interventions can be explained by kin selection, while the nature of dominant males' interventions suggests a control role. Interventions by males on behalf of juveniles may increase the formers' fitness.

Aggression↗

PubMed2004

Researching practice: the methodological case for narrative inquiry.

Research interest in the analysis of stories has increased as researchers in many disciplines endeavor to see the world through the eyes of others. We make the methodological case for narrative inquiry as a unique means to get inside the world of health promotion practice. We demonstrate how this form of inquiry may reveal what practitioners value most in and through their practice, and the indigenous theory or the cause-and-consequence thinking that governs their actions. Our examples draw on a unique data set, i.e. 2 two years' of diaries being kept by community development officers in eight communities engaged in a primary care and community development intervention to reduce postnatal depression and promote the physical health of recent mothers. Narrative inquiry examines the way a story is told by considering the positioning of the actor/storyteller, the endpoints, the supporting cast, the sequencing and the tension created by the revelation of some events, in preference to others. Narrative methods may provide special insights into the complexity of community intervention implementation over and above more familiar research methods.

Community Networks↗

PubMedDate not supplied

Evaluating the impact of case management dosage.

BACKGROUND: Because of the broad range of activities involved and high variance in clients' needs, it is challenging to measure the actual dose of case management in order to assess quality and manage outcomes. OBJECTIVE: The purpose of this research is to evaluate the impact of intervention dosage on client outcomes in different case management models within substance abuse treatment. METHOD: A descriptive and repeated measures analysis from a clinical trials data set measured the dosage of case management and evaluated impact on client outcomes. A sample of 598 clients from a substance abuse treatment facility was randomized into one of four groups, assessed at intake and then followed for 1 year. Three groups received a form of case management as an intervention (n= 437), and all clients received drug treatment. RESULTS: Clients who engaged (actively participated) in case management were less likely to have legal and family issues but more likely to have a chronic medical condition at baseline. Dosage factors differed significantly across treatment conditions. In general, dose was significantly related to outcomes in the legal and family domains. CONCLUSIONS: Although complex, case management intervention dosage can be measured using the model presented. Dosage determination aids cost-effective initiatives. Further research is needed to specify intervention protocols.

Adult↗

PubMed2004

Teaching empathy to first year medical students: evaluation of an elective literature and medicine course.

BACKGROUND: Empathy is critical to the development of professionalism in medical students, and the humanities-particularly literature-have been touted as an effective tool for increasing student empathy. This quantitative/qualitative study was undertaken to assess whether reading and discussing poetry and prose related to patients and doctors could significantly increase medical student empathy and appreciation of the relevance of the humanities for their own professional development. METHOD: In 2000-2001, first year students (n=22) volunteered for an eight-session literature and medicine elective and were randomly assigned to either immediate participation in the class or a wait-list group, who participated in the same class 6 months later. Complete pre- and post-intervention data for 16 students from both groups were obtained for two quantitative measures of empathy and an attitudes-toward-the-humanities scale. Students also participated in a qualitative group interview pre- and post-intervention. RESULTS: Empathy and attitudes toward the humanities improved significantly (p<0.01) after participation in the class when both groups of students were combined. The scaled treatment effect size was in the moderate range (> or =0.60 standard deviation units) for both measures that had statistically significant pre-to-post changes. Furthermore, student understanding of the patient's perspective became more detailed and complex after the intervention. Students were also more likely post-intervention to note ways reading literature could help them cope with training-related stress. CONCLUSION: A brief literature-based course can contribute to greater student empathy and appreciation for the value of humanities in medical education.

Adult↗

PubMed2006

Experience with coronary sinus lead implantations for cardiac resynchronization therapy in 244 patients.

INTRODUCTION: Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new method for the therapy of congestive heart failure (CHF). Because the intervention is more complex than regular pacemaker implantations, information on the feasibility and side effects of this method are of interest. METHODS: From 1999 to June 2005, CRT implantations were attempted in 244 patients (pts; mean age 64+/-12 years, range 14-90 years), 82% were male, 44% had coronary artery disease, 29% were in atrial fibrillation, 71 had preexisting pacemakers. RESULTS: In 97% of the pts the intervention was successful (27% of the systems with defibrillation capabilities). In 285 interventions, 255 CS leads were positioned according to CS vein anatomy in 130 posterolateral, 97 anterolateral and 28 anterior side branches (16 patients received 2 CS leads). Over-the-wire leads were used in 88%, 71% were additionally preshaped. We observed no mortality but 37 complications (12.5%): CS dissection in 9, CS perforation in 1, ventricular fibrillation in 4, asystole in 5, pulmonary edema in 1, pneumothorax in 2, need for early CS lead revision in 19 (dislodgement n=7, phrenic nerve stimulation n=12) and infection with explantation in 2 cases. An improvement in NYHA functional class was found in 88% of pts (only 55% if anterior lead position). CONCLUSION: Perioperative complications during CS lead implantation occur in 10-15% of cases. Most patients responded well to CRT. Patients should be informed about the possible need for a reoperation. During implantation, immediate defibrillation and stimulation capabilities must be available. Anterior lead positions should be avoided.

Adolescent↗

PubMed1996

Pathophysiology and management of VIPoma: a case study.

PURPOSE/OBJECTIVES: To review the pathophysiology and clinical treatment of VIPomas, neuroendocrine tumors that secrete vasoactive intestinal polypeptide, and VIPoma syndrome. DATA SOURCES: Published clinical treatments and case studies in the medical literature and case study data from a patient's medical record. DATA SYNTHESIS: VIPomas are rare neuroendocrine tumors that cause a syndrome of life-threatening symptoms. Clinical management is complex, yet little information is available in the medical and nursing literature to guide the clinician. CONCLUSIONS: Information about the pathophysiology and management of the disease may facilitate care of these patients. IMPLICATIONS FOR NURSING PRACTICE: A case study presentation provides an example of the care required by one patient with VIPoma. The nurse has an important role in assessing, educating, and caring for the patient with VIPoma. Interventions include managing complex fluid and electrolyte imbalances, chemotherapy administration and management of side effects, activity and rest alterations, safety issues, altered social roles, and educational needs regarding medications, central lines, and follow-up care.

Adult↗

PubMed2006

Transcatheter ablation through the cardiac veins in a patient with a biventricular device and left ventricular epicardial arrhythmias.

Left ventricular outflow tract (LVOT) may be a source of repeated premature ventricular complexes (PVCs). In symptomatic patients, radiofrequency catheter ablation (RFCA) can be effective, either from endocardial or from epicardial sites. A 50-year-old patient, with dilated cardiomyopathy (DCM) and severe left ventricular (LV) dysfunction, left bundle branch block (LBBB), New York Heart Association (NYHA) class IV, received a biventricular implantable cardioverter/defibrillator (ICD) in 2002. Despite drug therapy, PVCs were frequent (21.019/24 h) including prolonged runs, prompting ICD intervention. Premature ventricular complexes showed an inferior axis morphology, with an R/S ratio in V3>1, suggesting an LVOT origin. Despite the cardiac resynchronization therapy (CRT) device, successful RFCA was performed through the anterior venous branch, with a favourable clinical outcome. To our knowledge, this is the first case describing epicardial RFCA of a PVC focus from cardiac veins in the presence of a CRT device.

Cardiac Pacing, Artificial↗

PubMedDate not supplied

Intrinsically driven changes in gene interaction complexity. I. Growth of regulatory complexes and increase in number of genes.

A two-step process, previously considered in the literature, and here named coadaptational drive, is deemed to be largely responsible for both increases in the complexity of transcriptional control and increases in the total gene number, along lines of descent leading to more complex organisms. Coadaptational drive consists in a succession of modifications in the interaction among informational macromolecules, namely, structural decay spread by genetic drift and repair spread by selection. Increased genetic complexity, drawing on the opportunities offered by gene duplication, may be considered to be a secondary effect of such processes of decay and repair. The evolution toward higher regulatory complexity is thus considered to be obligatorily founded in part on random genetic drift. Increases in this complexity would represent primarily a trend intrinsic to the internal molecular environment, with the external environment having only to concur. Direct selection of mutations that increase complexity without the intervention of a phase of genetic drift is acknowledged likely to be a significant process as well, but it is claimed that a sequence of events of direct selection cannot be unlimited and will eventually stall, and that the roots of such a sequence ultimately are to be traced to an episode of coadaptational drive. Controller gene diseases, mostly mild, therefore seem to be essential for the evolution of increased biological complexity. The attempt is made to show or to confirm that (i) a conservative force (repair) provides a mechanism for the generation of novelty, (ii) a prominent part of selection, counterpart to Darwinian selection, originates from the internal environment and derives from the mechanics of genomic processes, and (iii) this selection is at times directional and leads to increases in complexity.

Animals↗

PubMed1996

Generation of in vitro natural cytotoxicity of horse lymphocytes against sarcoid-derived tumor cells not expressing major histocompatibility complex antigens.

OBJECTIVE: To analyze in vitro lymphocyte-mediated immune responses of horses with sarcoids against allogeneic sarcoid cells containing endogenous retrovirus but not expressing major histocompatibility complex antigens. DESIGN: Lymphocyte-mediated immune reactions were assessed by means of proliferative responses in mixed lymphocyte tumor cell culture (MLTC) assay and lymphocyte-mediated cytotoxicity against various equine target cells. ANIMALS: 12 horses with sarcoid tumors and 15 control horses. PROCEDURE: Blood lymphocytes were cocultured in MLTC with allogeneic sarcoid cells (Mc-1, BayMc-1), equine testis cells, or normal equine dermal fibroblasts. Lymphocytes were assayed for proliferative responses by [3H]thymidine uptake and for cytotoxicity against the same targets by 51Cr release assay. The lymphocyte populations were analyzed for some common surface markers. RESULTS: Lymphocytes from horses with sarcoids exerted an anamnestic proliferative response in MLTC against Mc-1 cells, but this procedure never generated cytotoxic lymphocytes. However, lymphocytes from all horses cultured in medium with 10% allogeneic serum only had selective. natural cytotoxicity against Mc-1 that was generated without DNA synthesis. Approximately 80% of the lymphocytes disappeared during culture; however the remaining population of small, viable lymphocytes indicated a decrease of CD4+ T lymphocytes, but numbers of T cells with receptors for Helix pomatia A hemagglutinin were unaffected. Few lymphocytes had Fc-receptors for IgG, were complement-reactive positive cells or were B cells expressing surface immunoglobulin. CONCLUSIONS: Results may indicate a natural defense system, which preferentially recognizes and lyses tumor cells that are deficient in surface expression of major histocompatibility complex antigens, without intervention of conventional T-cell receptors or antibodies.

Animals↗