New developments in the biomechanics of the diabetic foot

Biomechanical issues are now widely recognized as being important in the treatment of diabetic foot disease. The purpose of the present review is to identify advances that have occurred since the previous International Conference on the Diabetic Foot in 1995 in the understanding of foot biomechanics in relation to diabetes. Attention continues to be focused on the identification of a threshold plantar pressure that leads to tissue damage. Recent studies have suggested that peak barefoot pressure may be only 65% specific for the development of ulceration. The association between foot deformity and plantar pressure has been the subject of several quantitative studies, but new questions have been raised about the etiology of claw toes. The measurement of shear stress continues to be an elusive goal although several small studies have presented possibly feasible technical approaches. The importance of callus as a precursor to ulceration has been confirmed experimentally and quantitative measures of motor neuropathy have been presented. Although a number of new devices have been introduced as alternatives to the Total Contact Cast, few clinical studies of their efficacy are available yet. New information on the properties of insole materials has been published including data on changes with repeated cycling. Complications of prophylactic surgery have been shown to include a high rate of Charcot fractures. Two new series describing the fixation of such fractures have also been reported. Biomechanical issues have also been addressed in two sets of guidelines for treatment that have recently been published. These many studies confirm the central role of mechanical stress and its relief in the treatment of neuropathic foot problems in diabetes.     

Update of the economic analyses of the use of the colony-stimulating factors

The colony-stimulating factors have been used effectively in a variety of clinical settings to prevent febrile neutropenia and to assist patients receiving dose-intensive chemotherapy with or without stem cell support. Several studies have confirmed the clinical efficacy of the colony-stimulating factors used prophylactically in both solid tumors and the hematologic malignancies. The cost of these agents, along with their large scale clinical use, has prompted a number of economic investigations. Economic analyses based on measures of resource utilization derived from randomized clinical trials have provided febrile neutropenia risk threshold estimates for the cost saving use of prophylactic colony-stimulating factor. A number of important studies concerning the clinical and economic impact of these agents have been reported over the past year. These include a revised cost minimization study based on improved febrile neutropenia cost information and a cost-effectiveness analysis in the adjuvant breast cancer setting based on a clinical prediction model to select patients at high risk for neutropenic complications. Continuing clinical and economic evaluation along with updating of clinical practice guidelines is needed due to rapid technologic and clinical advances in this area.     

Some aspects of the wideband recording of the electrocardiogram

The physiological mechanisms responsible for the high frequency components of the electrocardiographic signals in different frequency ranges are still unknown. These components have been studied in the frequency domain as well as in the time domain. Numerous clinical and experimental studies have focused upon the incidence and interpretation of high frequency notches and slurs under different conditions in the myocardium. However, the analysis of the high frequency components appeared to be tedious and imprecise, and the interpretation of its results difficult and controversial, and strongly dependent upon empirically determined standards which still require thorough evaluation. Digital methods for processing electrocardiographic signals developed during the last decade have given rise to a variety of fast and reliable approaches for analyzing the information carried by the electrocardiogram. Many researchers have applied such methods to various clinical situations in human studies and to different kinds of interventions in animal studies. These developments prompted us to review research in the field of wideband recording of the electrocardiogram and to briefly discuss some of the aspects that still require elucidation.     

不同年龄段护士职业压力程度及对心理健康的影响

目的探讨不同年龄段护士职业压力程度及其对心理健康的影响。方法调查护士工作压力源量表及工作疲溃感量表,将测得数据进行处理后与全国常模数据进行比较,应用SAS6．12版进行统计分析。结果研究发现30-40岁的护士对抗工作压力的能力较强,且心理稳定程度较好。20～30岁的年轻护士感觉工作压力很大,但其心理防御与缓冲能力较强。而40岁以上的护士在管理及人际关系方面的问题中感觉到压力较大,心理健康问题也较突出结论针对长时间、工作量大、心理压力大的环境下工作的护士,必须采取有效的干预手段,以保证护理工作的质量。     

Hormonal regulation of the level of angiotensinogen in the blood plasma]

Literature examining angiotensinogen, a substrate of renin which forms the decapeptide angiotensin I which, in turn, forms the octapeptide angiotensin II, is surveyed. The regulation of the formation of angiotensinogen is thought to take place in the liver, but efforts to confirm this have been unsuccessful. The gonadotropic function of the hypophysis has been determined to have an influence on the level of angiotensinogen in the plasma. Much attention has been given to the adrenal glands as regulators of the formation of angiotensinogen in the liver. The sexual hormones have been thought to have a great influence on the regulation of angiotensinogen and are examined in regard to the influence of estrogens on the content of it in the plasma and to the hormonal regulation of the disruption of it, which takes place through hormonal regulation of the speed of renin secretion. The hormonal regulation of the excretion of angiotensinogen is shown diagrammatically.     

Unraveling the mysteries of classical preconditioning

Nearly two decades have passed since the first report about ischemic preconditioning. Although we do not yet know unequivocally what the final effector is, we have learned a lot about the signal transduction pathways that result in protection, and have some good prospects for the final step that results in survival or necrosis of the ischemic myocardium. Many investigators have contributed to our current knowledge. We were heartened to learn that four of our JMCC publications are included in the 20 top-cited papers in the journal's history. It is gratifying that our prior publications have generated some interest and stimulated important debate as documented by the high number of citations by scientists in the bibliographies of their own papers. In this document, we have been asked to reflect on those four papers and comment on where they have led us.     

Heart Failure Therapy at the Turn of the Century

Major changes in the treatment of heart failure have occurred in the last fifty years that have had a dramatic effect on its morbidity and mortality. Over two hundred years have passed since the demonstration of the benefit of digitalis in heart failure to the development of potent loop diuretics. The observation that vasodilators could improve both cardiac function and mortality led to the investigation of the Angiotensin Converting Enzyme Inhibitors (ACEI). Although these agents had significant vasodilator properties, their major benefit appears to be related to their ability to effect remodeling of the failing left ventricle. The most recent randomized clinical trials demonstrate that Beta Adrenergic Blocking agents can provide an incremental effect on both mortality and morbidity when added to therapy with ACEI. Although these agents have improved the outlook for the heart failure patient, they have had very little effect on the improvement of left ventricular function. Future research must be directed at methods to deal with this issue by either changing the contractile properties of the cardiomyocyte by pharmacologic or electrical therapy or by transplanting functional cells that can increase the number of functioning contractile units.     

Recapitulation of the round-table discussion--assessing the role of anti-tumour necrosis factor therapy in the treatment of rheumatoid arthritis

Clinical trials specifically targeting and neutralizing the cytokine, tumour necrosis factor (TNF), have recently provided evidence of efficacy and a promise of a novel approach for the treatment and management of rheumatoid arthritis (RA). With the evolving emergence of anti-TNF therapeutics, several unresolved issues have come to light, including the assessment of safety and efficacy of current therapies, study design for new agents and cost-benefit issues. During an international meeting of leading rheumatologists and specialists, the majority opinion regarding the use of anti-TNF therapy was that these agents are most appropriate in patients with active disease who have insufficient response to methotrexate, which is presently considered the standard for RA treatment. Anti-TNF therapy was also recommended in patients with active disease unable to tolerate methotrexate therapy, or who have not responded to at least two other disease-modifying anti-rheumatic drugs (DMARDs). In patients with RA who have serious infection or malignancy, the use of anti-TNF therapies was not advised. Time, experience and clinical data from recently completed and currently ongoing studies of infliximab and etanercept, which will be available in the future, will help determine the ultimate role of such targeted therapeutics. Additional data on anti-TNF therapeutics as monotherapy or in various combinations are still needed to achieve maximum disease control safely with currently available DMARDs.     

Recent advances in the management of hypertension in the elderly

Important new advances have occurred in our understanding and approach to management of high blood pressure in the elderly. New clinical trials have re-emphasized the risk of development of cardiovascular and cerebrovascular complications associated with isolated elevations in systolic blood pressure as well as the safety and efficacy of interventions to reduce blood pressure. These trials have shown that systolic blood pressure can be reduced by interventions such as weight loss, restriction of dietary sodium intake, and drugs. In several new trials, the long-acting dihydropyridine calcium channel blockers have been found to be safe and effective in these patients but not superior to other drugs. As in younger individuals with hypertension, drug therapy should be targeted to address comorbidity. Education of primary care physicians concerning these new findings is the next step in reducing the morbidity and mortality of this common problem in the elderly.     

Use of the early invasive approach in the management of acute coronary syndromes

Large randomized clinical trials of early invasive versus conservative strategy in patients with non-ST-elevation acute coronary syndromes (NSTE ACS) have been published recently. These studies have clearly shown that intermediate and high-risk patients presenting with NSTE ACS have better outcomes when referred early to cardiac catheterization. Patients who are referred early to cardiac catheterization have a reduction of death, myocardial infarction, and recurrent ischemia, and also have shorter hospital stays. Guidelines recommend referral to cardiac catheterization for intermediate and high-risk NSTE ACS patients within the first 48 hours of presentation. Despite these recommendations, data from a large nationwide registry show that the majority of high-risk patients with NSTE ACS are not being managed with an early invasive strategy.     

Recent advances in the management of hypertension in the elderly

Important new advances have occurred in our understanding and approach to management of high blood pressure in the elderly. New clinical trials have re-emphasized the risk of development of cardiovascular and cerebrovascular complications associated with isolated elevations in systolic blood pressure as well as the safety and efficacy of interventions to reduce blood pressure. These trials have shown that systolic blood pressure can be reduced by interventions such as weight loss, restriction of dietary sodium intake, and drugs. In several new trials, the long-acting dihydropyridine calcium channel blockers have been found to be safe and effective in these patients but not superior to other drugs. As in younger individuals with hypertension, drug therapy should be targeted to address comorbidity. Education of primary care physicians concerning these new findings is the next step in reducing the morbidity and mortality of this common problem in the elderly.     

Molecular methods in the diagnosis of infections in the immunocompromised host

Despite recent developments, infection remains a major obstacle to a successful outcome in transplantation. Molecular methods have allowed for earlier diagnosis and have proven to be powerful tools for analysing the epidemiology of infectious diseases. More recently, some of these molecular methods have been commercialized, enabling standardized diagnostic techniques to be used in multicentre trials.     

Functional consequences of mutations in the autophagy genes in the pathogenesis of Crohn's disease

Genome-wide association studies have highlighted a number of genes involved in autophagy, which are of potential importance in the pathogenesis of Crohn's disease (CD). The associated polymorphisms in ATG16L1 and IRGM have been confirmed, and functional studies have begun to shed light on how they link to CD pathogenesis. In this review we consider the most salient aspects of this rapidly expanding field.     

The role of sexually transmitted infections in the evolution of the South African HIV epidemic

Objectives To assess the extent to which sexually transmitted infections (STIs) have contributed to the spread of HIV in South Africa and to estimate the extent to which improvements in STI treatment have reduced HIV incidence. Methods A mathematical model was used to simulate interactions between HIV and six other STIs (genital herpes, syphilis, chancroid, gonorrhoea, chlamydial infection and trichomoniasis) as well as bacterial vaginosis and vaginal candidiasis. The effects of STIs on HIV transmission probabilities were assumed to be consistent with meta‐analytic reviews of observational studies, and the model was fitted to South African HIV prevalence data. Results The proportion of new HIV infections in adults that were attributable to curable STIs reduced from 39% (uncertainty range: 24–50%) in 1990 to 14% (8–18%) in 2010, while the proportion of new infections attributable to genital herpes increased. Syndromic management programmes are estimated to have reduced adult HIV incidence by 6.6% (3.3–10.3%) between 1994 and 2004, by which time syndromic management coverage was 52%. Had syndromic management been introduced in 1986, with immediate achievement of 100% coverage and a doubling of the rate of health seeking, HIV incidence would have reduced by 64% (36–82%) over the next decade, but had the same intervention been delayed until 2004, HIV incidence would have reduced by only 5.5% (2.8–9.0%). Conclusions Sexually transmitted infections have contributed significantly to the spread of HIV in South Africa, but STI control efforts have had limited impact on HIV incidence because of their late introduction and suboptimal coverage.     

Pharmacologic treatment of the stunned myocardium: the concepts and the challenges

During the past two decades (i.e., since 1980), in excess of 1000 published papers have focused on the phenomenon of the 'stunned myocardium', with many of these studies seeking to identify mechanisms-based treatment strategies to attenuate post-ischemic contractile dysfunction. Early investigations focused largely on abrogating the deleterious effects of oxygen-derived free radicals and unfavorable alterations in calcium homeostasis, both considered to contribute significantly to the pathogenesis of the stunned myocardium. More recently, favorable results have also been obtained using a somewhat different paradigm: that is, attempting to capitalize on endogenous cardioprotective mediators, most notably adenosine, nitric oxide, and the ATP-sensitive potassium channel. Now that potential therapeutic candidates have been identified in the experimental laboratory, the as-yet unmet challenge is to translate this information into the design of effective pharmacologic therapies to treat myocardial stunning in the clinical arena.     

Management of dyspepsia at the beginning of the twenty-first century

Abstract
Dyspepsia remains a frequent intercurrent management problem for the non-gastroenterologist. However, the causes for dyspepsia have changed markedly in recent decades. In contrast to gastro-oesophageal reflux ­disease, both gastro-oesophageal malignancy and peptic ulcer disease have become uncommon causes for ­dyspepsia. Concurrent with these changes, management strategies for dyspepsia have changed. Once aware of these changes the non-gastroenterologist can effectively manage the majority of patients with dyspepsia. The present paper reviews these key changes in dyspepsia management. (Intern Med J 2003; 33: 604−609)     

Familial aggregation of defects of the left-sided structures of the heart

A family is described where a mother and her three children had left heart defects. Three members of a second family were also noted to have such defects. This experience adds support to the hypothesis that in some families, such defects may have an incidence of recurrence higher than the 3% predicted by a multifactorial model.     

Quality of Care for Older Persons at the Dawn of the Third Millennium

During the past quarter century, researchers, providers, insurers, and governmental agencies have devoted considerable effort to improving and standardizing the quality of health care provided to older persons. Because older persons differ from younger persons as a result of their life expectancy, disease prevalence and comorbidity, social resources, goals of treatment, and preferences for care, defining and measuring quality of care has been more difficult for this age group. Nevertheless, several decades of research have led to reliable, although imperfect, methods of measuring quality, including those for geriatric conditions.
Using these measurement approaches, a variety of studies using different patient populations and sampling strategies have consistently identified deficiencies in quality of care provided to older persons. Moreover, efforts to improve quality of care for older persons have been difficult to design, implement, and sustain. Some have been successful, including having effects on outcome measures, but have not made the transition from research to clinical settings. Others have used quality improvement methods to improve the care of diseases (e.g., diabetes mellitus, congestive heart failure) that commonly affect older persons. However, the lack of alignment of incentives between providers and insurers for most older persons is a major barrier to this approach. In addition, there is no concerted effort among providers, regulatory agencies, and insurers to move the quality-of-care agenda for most Medicare recipients. Despite substantial progress in defining and measuring high-quality care for older persons, the goal of ensuring that older persons receiving such care remains a distant hope.     

Impact of temperature on the time required for the establishment of primordial biochemistry, and for the evolution of enzymes

All reactions are accelerated by an increase in temperature, but the magnitude of that effect on very slow reactions does not seem to have been fully appreciated. The hydrolysis of polysaccharides, for example, is accelerated 190,000-fold when the temperature is raised from 25 to 100 °C, while the rate of hydrolysis of phosphate monoester dianions increases 10,300,000-fold. Moreover, the slowest reactions tend to be the most heat-sensitive. These tendencies collapse, by as many as five orders of magnitude, the time that would have been required for early chemical evolution in a warm environment. We propose, further, that if the catalytic effect of a "proto-enzyme"--like that of modern enzymes--were mainly enthalpic, then the resulting rate enhancement would have increased automatically as the environment became cooler. Several powerful nonenzymatic catalysts of very slow biological reactions, notably pyridoxal phosphate and the ceric ion, are shown to meet that criterion. Taken together, these findings greatly reduce the time that would have been required for early chemical evolution, countering the view that not enough time has passed for life to have evolved to its present level of complexity.