Development Of More Effective Methods Research Articles

Assessing physical and cognitive function of older adults in continuing care retirement communities: Who are we recruiting?

PurposeIn partnership with six Continuing Care Retirement Communities (CCRCs), the current study focused on the feasibility of recruiting a representative sample of residents and then assessing their functional health. Material and MethodsWith our guidance, each of the six CCRCs recruited a volunteer (V-Group) and random (R-Group) sample of independent living residents. We provided face-to-face training and ongoing remote electronic support to the CCRC staff on the testing battery and the Web-based data entry system. The testing battery was consisted of demographic, physical function, and psychosocial assessments. ResultsAfter training, CCRC staff were receptive to the study goals and successfully used the data entry Website. In the V-Group (N=189), 76% were already participating in CCRC wellness programs. We attempted to recruit a random, unbiased (R-Group) sample of 20% (n=105) of eligible residents; however, only 30 consented to be tested and 70% of this group (21/30) were also already participating in a wellness program. Mean age of all participants was 82.9years. The V-Group had a higher Short Physical Performance Battery (SPPB) total score (least squares mean [SE], 9.4 [0.2] vs 8.2 [0.4], p=0.014) and SPPB gait speed component score (3.5 [0.1] vs 3.0 [0.2], p=0.007) and spent more time doing moderate-to-vigorous physical activity (300 [21] vs 163 [49] min/week, p=0.013) compared to the R-Group. ImplicationsWhile it is feasible to recruit, assess and transmit data on residents' functional health in partnership with CCRCs, population validity was severely compromised. Attention needs to be given to the development of more effective methods to recruit less interested residents.

Coupling forces exerted on chain saws by inexperienced tree fellers

Prolonged, intensive exposure to vibrations produced by vibrating tools could cause non-specific disorders in upper extremities of the operator, referred to as hand-arm vibration syndrome (HAVS). The severity of HAVS is affected by the magnitude of coupling forces exerted on the tool handle. The aim of the study was to measure the coupling forces exerted by inexperienced tree fellers on chain saws. Forces exerted by inexperienced tree fellers were compared to those of professional lumberjacks to investigate the relationship between the coupling forces and the experience of the chain saw operator. Coupling forces exerted on chain saws by inexperienced workers, using right and left hands, were measured in a group of 19 students. All measurements were done in forest environment. Coupling forces registered among trainees were about 5 N higher than forces exerted by professional lumberjacks. Our findings suggest that experienced workers use smaller forces than trainees. Relevance to industryThis study shows that inexperienced tree fellers exert larger coupling forces on chain saws than professional forestry workers. Transmissibility of vibration to the hand and arm, which depends on coupling forces, is increased in a group of non-experienced lumberjacks. These results may constitute a starting point for the further development of more effective methods for assessing the risks of vibration exposure and for developing better tools and vibration-reducing devices.

Applying Cognitive Models of Deception to National Security Investigations: Considerations of Psychological Research, Law, and Ethical Practice

The current threat of global terrorism has sparked a renewed interest in the development of more effective methods for the detection of deception. In the United States, the American Psychological Association (APA)—spurred by torture allegations involving terrorist suspects—established guidelines for professional practice regarding investigative methods that could be conceptualized as coercive. As affirmed by APA, psychological research can play an active and ethical role in the development of standardized methods for the detection of deception. Instead of focusing on external sources of terrorism, this conceptual paper argues for programmatic research on insider threats, specifically risks to national security posed by government and other employees. In briefly reviewing deception research, recent investigations of cognitive loads and deceptions hold particular promise, especially studies that systematically manipulate levels of cognitive load. These methods can be extended to collateral sources, further minimizing ethical concerns while broadening the scope of deception investigation.

Adaptation to extreme stress: post-traumatic stress disorder, neuropeptide Y and metabolic syndrome

The prevalence rates of obesity and metabolic syndrome are on the rise in the United States. Epidemiological surveys suggest that the rates of these medical conditions are especially high among persons with psychiatric disorders, including post-traumatic stress disorder (PTSD). A variety of factors are thought to contribute to the risk for metabolic syndrome, including excessive caloric intake, decreased activity and energy expenditure, use of certain medications, stress and genetic influences. Recent research demonstrates that stress, acting through the neuropeptide Y (NPY) and glucocorticoid systems, potentiates the development of obesity and other aspects of metabolic syndrome in mice fed a high caloric, fat and sugar diet. Alterations in the NPY and glucocorticoid systems also impact behavioral adaptation to stress, as indicated by studies in animals and persons exposed to severe, life-threatening or traumatic stress. The following review examines the biology of the NPY and neuroactive steroid systems as physiological links between metabolic syndrome and PTSD, a paradigmatic neuropsychiatric stress disorder. Hopefully, understanding the function of these systems from both a translational and systems biology point of view in relation to stress will enable development of more effective methods for preventing and treating the negative physical and mental health consequences of stress.

Advances in Rift Valley fever research: insights for disease prevention

The purpose was to review recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates. RVFV continues to extend its range in Africa and the Middle East. Better definition of RVFV-related clinical syndromes and human risk factors for severe disease, combined with early-warning systems based on remote-sensing, simplified rapid diagnostics, and tele-epidemiology, hold promise for earlier deployment of effective outbreak control measures. Advances in understanding of viral replication pathways and host cell-related pathogenesis suggest means for antiviral therapeutics and for more effective vaccination strategies based on genetically engineered virus strains or subunit vaccines. RVFV is a significant health and economic burden in many areas of Africa, and remains a serious threat to other parts of the world. Development of more effective methods for RVFV outbreak prevention and control remains a global health priority.

Quantitative Phosphoproteome Analysis of Lysophosphatidic Acid Induced Chemotaxis Applying Dual-Step 18O Labeling Coupled with Immobilized Metal-Ion Affinity Chromatography

Reversible protein phosphorylation is a central cellular regulatory mechanism in modulating protein activity and propagating signals within cellular pathways and networks. Development of more effective methods for the simultaneous identification of phosphorylation sites and quantification of temporal changes in protein phosphorylation could provide important insights into molecular signaling mechanisms in various cellular processes. Here we present an integrated quantitative phosphoproteomics approach and its application for comparative analysis of Cos-7 cells in response to lysophosphatidic acid (LPA) gradient stimulation. The approach combines trypsin-catalyzed (16)O/ (18)O labeling plus (16)O/ (18)O-methanol esterification for quantitation, a macro-immobilized metal-ion affinity chromatography trap for phosphopeptide enrichment, and LC-MS/MS analysis. LC separation and MS/MS are followed by neutral loss-dependent MS/MS/MS for phosphopeptide identification using a linear ion trap (LTQ)-FT mass spectrometer. A variety of phosphorylated proteins were identified and quantified including receptors, kinases, proteins associated with small GTPases, and cytoskeleton proteins. A number of hypothetical proteins were also identified as differentially expressed followed by LPA stimulation, and we have shown evidence of pseudopodia subcellular localization of one of these candidate proteins. These results demonstrate the efficiency of this quantitative phosphoproteomics approach and its application for rapid discovery of phosphorylation events associated with LPA gradient sensing and cell chemotaxis.

Commentary on a theory of hypnosis based on principles of conditioning and inhibition Part II: benefits of the theory

AbstractThis is Part II of a commentary which places in the contemporary context, ‘A theory of hypnosis based on principles of conditioning and inhibition (Barrios, 2001).’ Whereas Part I includes evidence both in support of the theory and comparisons with other contemporary theories, Part II presents some of the benefits of the theory which includes: (1) a further understanding of the hallucinogens, biofeedback, higher‐order conditioning, placebos and religion; (2) development of more effective methods of hypnotic induction; (3) development of more effective methods for giving post‐hypnotic suggestions; (4) and development of Self‐Programmed Control (SPC; Barrios, 1973b, 1985), a positive‐oriented behavioural improvement programme aimed at producing self‐actualization, greater self‐efficacy, and higher emotional intelligence. I present the positive results of SPC's application in the areas of: education, welfare, industry, medicine, and drug rehabilitation. Copyright © 2007 British Society of Experimental & Clinical Hypnosis. Published by John Wiley & Sons, Ltd.

Communication and Teamwork

Communication and Teamwork

Burn Injury Pain: The Continuing Challenge

The development of more effective methods of relieving pain associated with burn injury is a major unmet medical need. Not only is acute burn injury pain a source of immense suffering, but it has been linked to debilitating chronic pain and stress-related disorders. Although pain management guidelines and protocols have been developed and implemented, unrelieved moderate-to-severe pain continues to be reported after burn injury. One reason for this is that the intensity of pain associated with wound care and rehabilitation therapy, the major source of severe pain in this patient population, varies widely over the 3 phases of burn recovery, making it difficult to estimate analgesic requirements. The effects of opioids, the most commonly administered analgesics for burn injury procedural pain, are difficult to gauge over the course of burn recovery because the need for an opioid may change rapidly, resulting in the overmedication or undermedication of burn-injured patients. Understanding the mechanisms that contribute to the intensity and variability of burn injury pain over time is crucial to its proper management. We provide an overview of the types of pain associated with a burn injury, describe how these different types of pain interfere with the phases of burn recovery, and summarize pharmacologic pain management strategies across the continuum of burn care. We conclude with a discussion and suggestions for improvement. Rational management, based on the underlying mechanisms that contribute to the intensity and variability of burn injury pain, is in its infancy. The paucity of information highlights the need for research that explores and advances the identification of mechanisms of acute and chronic burn injury pain. Researchers continue to report that burn pain is undertreated. This review examines burn injury pain management across the phases of burn recovery, emphasizing 3 types of pain that require separate assessment and management. It provides insights and suggestions for future research directions to address this significant clinical problem.

Personalized medicine - pharmacogenetics.

10.2217/17410541.3.1.9 © 20 The recent report commissioned by the Royal Society, Personalised Medicines: Hopes and Realities, focuses on the current status of pharmacogenetics, one of the major fields on which the concept of personalized medicine hangs much of its hopes. While seeing a major role in genomics for drug discovery and development, the report is much more cautious about the application of pharmacogenetics in the clinic. The clinical possibilities of pharmacogenetics range from the molecular subdivision of common diseases into different diagnostic and therapeutic entities, through to the development of more effective methods of improving the efficacy of drugs, to the reduction in the side effects of drug therapy. It seems likely that progress will be made in the subdivision of common diseases into better defined entities. This is already happening in the cancer field and has started to provide highly specific targets for drugs based on the particular molecular pathology of different forms of cancer. Although progress is likely to be slow, it is quite possible that similar molecular targets will follow the improved definition of different forms of other common diseases, type II diabetes and cardiovascular disease, for example. It is when considering the improvements in efficacy or a reduction in unwanted side effects that the role of pharmacogenetics becomes less certain. It has been known for many years that certain well defined monogenic variants have a highly significant effect on how certain drugs are handled, yet this information is rarely used in the clinic. The reasons for this are difficult to define; the perceived complexity of genetic testing, belief that careful observation of drug response is adequate, and simple ignorance that such polymorphisms exist, may be part of the reason. However, more recently there has been an extensive acquisition of information regarding the molecular basis for genetic variability in drug response yet, to date, none of this information has been examined for its practicability in the clinic and community. The report therefore concluded that it was now vital that each drug polymorphism was tested for its clinical value in large, controlled community studies. However, these will not be easy. The difficulty in defining the phenotype of efficacy or unwanted effects is not easy, the metabolism of many drugs will come under the control of more than one gene, and it will clearly have to be seen to be cost effective to include genetic testing in therapeutic regimes. Also, will genetic testing really be more effective than careful monitoring of response on the part of doctors? However, it is encouraging to hear that several large-scale studies of this type with commonly used drugs such as warfarin are now underway. Should it turn out that genetic testing is both therapeutically effective and cost effective, there will remain some considerable organizational problems before pharmacogenetics becomes established routinely in the clinic. Who will perform the testing, and, even more importantly, who will provide the appropriate information to patients regarding what they are being tested for? A debate with the public, carried out during the preparation of the report, suggested that while patients understood the principles of pharmacogenetics, they were extremely concerned about who would supply them with the appropriate information; clearly a major education program will have to precede any such changes in clinical practice. Further development of this field has very important implications for the education of doctors, nurses, pharmacists, and other health professionals. Finally, the clinical application of pharmacogenetics raises a number of ethical issues that were discussed in a recent report by the Nuffield Bioethics Council. These will also need to be addressed before pharmacogenetics reaches the clinic. In short, while the report was cautiously optimistic about the development of pharmacogenetics for clinical practice, it emphasized the vital importance of testing each drug in the community on a one-to-one basis with cost–benefit analysis, and emphasized some of the important organizational and educational improvements that would need to be in place before this form of personalized medicine can make a major impact in clinical practice.

Protein kinase C and myocardial calcium handling during ischemia and reperfusion: lessons learned using Rhod-2 spectrofluorometry.

We sought to assess myocardial Ca (2+) handling and excitation-contraction coupling in surgically relevant models of ischemia-reperfusion injury and to clarify the importance of protein kinase C (PKC) for cardioprotection. Experimentally, surgical ischemia and reperfusion can only be mimicked in intact perfused heart models. We introduced the long-wavelength fluorescent Ca (2+) indicator Rhod-2 for real-time recording of cytosolic Ca (2+) transients in Langendorff-perfused rabbit, rat, and mouse hearts, and utilized it to study the impact of PKC on myocardial Ca (2+) handling during ischemia and reperfusion. We first established that the dissociation constant for Rhod-2 and Ca (2+) must be adjusted to account for changes in pH and temperature during ischemia and reperfusion. Based on this method, we determined the time-course and extent of cytosolic Ca (2+) accumulation during myocardial ischemia, which is associated with translocation of the PKC isoforms alpha and epsilon between the cytosolic and particulate compartments in cardiomyocytes. The PKC translocation is mediated by activation of phosphatidyl-inositol-specific phospholipase C (PI-PLC), and represents a cardioprotective mechanism. Finally, we studied the mechanism of action of PKC and found that it both limits the accumulation of cytosolic Ca (2+) during reperfusion and attenuates contractile protein Ca (2+) sensitivity via phosphorylation of troponin I. Rhod-2 spectrofluorometry is a valuable tool for assessment of cytosolic Ca (2+) in surgically relevant experimental models and can aid the development of more effective methods for myocardial protection.

Bacteria and wound healing

Wound healing is a complex process with many potential factors that can delay healing. There is increasing interest in the effects of bacteria on the processes of wound healing. All chronic wounds are colonized by bacteria, with low levels of bacteria being beneficial to the wound healing process. Wound infection is detrimental to wound healing, but the diagnosis and management of wound infection is controversial, and varies between clinicians. There is increasing recognition of the concept of critical colonization or local infection, when wound healing may be delayed in the absence of the typical clinical features of infection. The progression from wound colonization to infection depends not only on the bacterial count or the species present, but also on the host immune response, the number of different species present, the virulence of the organisms and synergistic interactions between the different species. There is increasing evidence that bacteria within chronic wounds live within biofilm communities, in which the bacteria are protected from host defences and develop resistance to antibiotic treatment. An appreciation of the factors affecting the progression from colonization to infection can help clinicians with the interpretation of clinical findings and microbiological investigations in patients with chronic wounds. An understanding of the physiology and interactions within multi-species biofilms may aid the development of more effective methods of treating infected and poorly healing wounds. The emergence of consensus guidelines has helped to optimize clinical management.

A TEST: CAN STEWARDSHIP THEORY SERVE AS A SECOND CONCEPTUAL FOUNDATION FOR ACCOUNTABILITY METHODS IN CONTRACTED HUMAN SERVICES?

Stewardship theories have been proposed recently as the possible basis for the reform of roles and responsibilities of principals and agents in government contracted service relations, and for the design and development of more effective methods for ensuring accountability (and quality) in contracted human services. This article reports on an empirical field study that tested the relationship between two values-related independent variables associated with stewardship theories–values convergence and altruistic (public service) values–and service quality of contracted providers. The study did not demonstrate a positive relationship between the independent variables and service quality, but the authors argue that stewardship theory should not be dismissed yet as a conceptual foundation for the development of methods for ensuring accountability in human services contracting. They urge additional research in this area.

New Advances in Preventing and Treating Serious Surgical Infection: Introduction

© E.I.F.T. srl Firenze ISSN 1120-009X As is true in all of medicine, prevention is the ultimate solution to surgical infection. It is therefore not surprising that a major and consistent effort in the development of surgery has been, and continues to be, an extensive attempt to achieve surgery without complicating infection. It is also true that the wide and ever expanding use of surgical management in medicine today speaks to the success achieved. Our ability to deal with infection has been substantially improved, particularly over the last decades. This improvement was made possible by extensive research. As examples: post operative wound infection has been markedly reduced through studies providing a more exact understanding of the mechanisms of natural host defenses. These investigations have developed the concept of an “effective period of preventive antibiotic activity” which when utilized clinically insures the timely use of preoperative antibiotics and a marked reduction in postoperative infection 1,2. Further, with a more exact knowledge of the altered physiology of injury it is possible to carry out highly effective resuscitation of injured patients. The use of recent advances in diagnostic ability through computed tomography (CT) and Magnetic Resonance Imaging (MRI) allows the immediate, accurate recognition and definitive surgical repair of visceral, soft tissue or bony injuries or abnormalities, remarkably reducing the incidence of serious sepsis following both injury or problems produced by disease. Never the less, although reduced, infection complicating treatment remains a limiting factor in the further development of surgery as a therapeutic tool. This limitation is particularly marked in the application of surgery to presently unsolved medical problems; especially those involving: patients with serious physiologic or immunologic defects, patients requiring immunosuppression and patients best treated by the use of tissue engineered medical devices. Progress in these areas is, to a considerable extent, dependent on the development of more effective methods of preventing or dealing with infection. Therefore, throughout the history of modern surgery there has been a substantial effort to eliminate infection. As an extension of these efforts research over the past decade has concentrated on methods to restore or supplement host defense. In evaluating this work it is important to recognize that there are two basic clinical situations where infection interacts with surgery to limit its effectiveness as a therapeutic New Advances in Preventing and Treating Serious Surgical Infection: Introduction

Development of more effective methods of normalization and application at braking in turn test

Development of more effective methods of normalization and application at braking in turn test

Update on media for isolation of Enterobacteriaceae from foods

Testing for `total' Enterobacteriaceae, coliforms and Escherichia coli as marker organisms in foods and detection of specific pathogens of the family Enterobacteriaceae, including pathogenic E. coli, Salmonella, Shigella and Yersinia spp. is widely applied in many food control laboratories. This review describes some recent developments in culture media for these organisms. Methods for enumeration of E. coli include the standard MPN technique, a membrane-filter method and the use of media containing chromogenic and fluorogenic indicators for β- d-glucuronidase (GUD) activity. Shiga toxin-producing E. coli O157 strains usually do not ferment sorbitol and are GUD-negative. These characteristics are used in selective media for these organisms, such as cefixime tellurite sorbitol MacConkey agar. For the detection of salmonellae, motility enrichment in Modified Semisolid Rappaport–Vassiliadis (MSRV) medium shows equal or better results than the use of standard Rappaport–Vassiliadis broth. Addition of nitrofurantoin to diagnostic semisolid salmonella agar and to xylose lysine desoxycholate agar favours the isolation of S. enteritidis. Recently developed salmonella media use different selective and diagnostic properties, such as acid formation from propylene glycol, glucuronate fermentation, fermentation of glycerol and addition of Tergitol 4 as selective agent. The isolation of Shigella spp. from foods is rather difficult and further evaluation of suggested isolation systems and the development of more effective methods for the isolation of this pathogen are needed. Yersinia enterocolitica includes both pathogenic and nonpathogenic biotypes and serogroups. As no single procedure will recover all pathogenic strains of Y. enterocolitica, the use of two isolation procedures in parallel is recommended.

Neutralization of bee venom lethality by immune serum antibodies.

The lethal effects of Africanized honey bee venom depend on the absorption of venom delivered during simultaneous sting attacks by large numbers of bees. The hypothesis that antibodies to whole bee venom and bee venom components could neutralize the lethal effect of bee venom was tested. Antibodies from beekeepers and immunized rabbits were incubated with bee venom and neutralization was studied by survival of intravenously injected mice. Beekeeper serum antibodies were found effective in protecting mice challenged with whole venom, and serum from rabbits immunized with phospholipase A2 (PLA2) was effective in protection against lethal effects of PLA2. Serum antibodies from rabbits immunized with whole venom or melittin were ineffective in neutralizing whole venom in vivo and had low titers in a venom enzyme-linked immunosorbent assay. The results suggest the need for development of more effective methods for raising antitoxic antibodies to bee venom components in other animals as a means of developing an antiserum that would be effective for treatment of human victims of multiple bee stings.

Treatment of Alzheimer's disease: future directions

Following the introduction of tacrine hydrochloride (Cognex) in the United States and several other countries, researchers are pursuing two broad therapeutic strategies for Alzheimer's disease (AD). The first involves identifying agents or combinations of agents whose actions can compensate for the considerable cerebral damage that has typically occurred by the time the diagnosis of AD is made. Such therapeutic approaches include the development of additional cholinesterase inhibitors, agents that work on the receptors of other systems damaged by the disease process, and anti-inflammatory and immunomodulatory agents. The second and ultimately more promising strategy involves the development of approaches to retard, halt, or even prevent disease progression. Such protective approaches, which depend on the development of more effective methods for predicting and diagnosing AD, include the administration of nerve growth factor and other neurotrophins and the use of pharmacologic or genetic interventions to limit amyloid deposition and the formation of neurofibrillary tangles.

Polymerase chain reaction-based DNA fingerprinting of Enterococcus faecium isolated from intramammary infections of dairy cows

Twenty of 71 cows in a dairy herd that calved between 1 November 1990 and 31 January 1991 had clinical or subclinical mastitis associated with Enterococcus faecium during early lactation. Forty-two E. faecium isolates were cultured from samples of mammary secretions collected from these 20 cows during this period. In the following calving season between 1 November 1991 and 31 January 1992, five isolates of E. faecium were identified from mammary secretion of four of 85 cows. All four cows had E. faecium intramammary infections within 14 days after calving. Isolates were subtyped using a polymerase chain reaction (PCR)-based DNA fingerprinting method. In addition, plasmid analysis was performed. PCR-based DNA fingerprinting differentiated the 47 isolates into four distinct subtypes. Five of six clinical mastitis isolates of E. faecium belonged to Subtype 2, and E. faecium Subtype 1 was the only subtype that was isolated from both calving seasons. PCR-based DNA fingerprinting was useful in tracing an infection of the same subtype in a cow over a period of time. New intramammary infections by different subtypes were identified also. Two plasmids of 4.8- and 5.1-kb were observed in seven strains identified as Subtype 3 by PCR-based DNA fingerprinting. Results of this study suggest that E. faecium can be an important cause of mastitis during early lactation. PCR-based DNA fingerprinting was useful for subtyping E. faecium isolates. Use of this technique could aid in understanding the epidemiology of bovine mastitis and facilitate development of more effective methods to control intramammary infections in dairy cows.

Experimental Bacterial Endocarditis and Proliferative Glomerulonephritis: Description of Method of Production Utilizing Bilateral Lower Extremity or Single Aorta-Vena Cava Arteriovenous Fistulas

SUMMARY AND CONCLUSIONS 1)By combining the effects of systemic cardiovascular stress produced by large arteriovenous fistula loads with bacteremia, a new method has been described for the experimental production of endocarditis and acute diffuse proliferative glomerulonephritis in dogs. 2)Bilateral lower extremity (iliac and femoral), or single aorta-vena cava fistulas are effective for use in this experimental method. 3)Seventeen unoperated normal dogs were given injections of bacterial organisms in numbers up to 14,000 times the numbers of bacteria of the same species and strains as were followed by heart valve or kidney lesions in the dogs with large arteriovenous fistula loads. There was in no instance the occurrence of either endocarditis nor glomerulonephritis in these normal dogs. 4)Likewise, in 10 dogs with single femoral arteriovenous anastomoses receiving intravenous injections of bacteria in comparable numbers, neither endocarditis nor glomerulonephritis occurred. 5)Because of the absence of lesions in the unoperated normal dogs and dogs with single femoral arteriovenous shunts given the same bacteria in the same or much larger numbers than given to the animals with large fistulas subsequently showing valvular or renal lesions, it is concluded that the increased work of the heart plays a major role in determining the susceptibility of these animals to endocarditis and glomerulonephritis. 6)The pathogenesis of these experimental observations depends upon the fact that increasing the work of the heart by means of large arteriovenous fistula loads create or set in motion certain mechanical and, or endocrine alterations which in turn produce a specific and significant increase (up to 14,000 times) in the susceptibility of the endothelial surfaces of the heart and kidneys to bacterial infection. The factual data supporting these conclusions are presented. 7)By utilizing these experimental methods, it may be possible to identify more precisely the physiological alterations which occur in response to increased cardiovascular work and which are apparently responsible for this great increase in susceptibility to bacterial infection observed in these studies. Such accomplishments, might forecast the development of more effective methods of prophylaxis and therapy for endocarditis, glomerulonephritis, and possibly for bacterial infections in general.