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PubMed2006

Evolving role of surgery, radiation, hormone therapy, and chemotherapy in high-risk locally advanced prostate cancer.

Locally advanced prostate cancer encompasses several disease states that vary in the risk for progression and recurrence after initial treatment. Further, the optimal treatment strategies for locally advanced prostate cancer are continuing to evolve, reflecting the complex nature of this disease state. For many patients, clinical experience demonstrates that a combined approach of locally directed therapy and systemic therapy is likely to provide better long-term outcome than single-modality therapy. Randomized studies have established hormone ablation with external-beam radiation as an important form of treatment for this group of patients. However, additional progress needs to be made, particularly in the subgroup of patients with very high-risk disease features. As the optimal integration of local and systemic treatments becomes more clearly defined, the long-term prognosis for patients with high-risk locally advanced prostate cancer will improve.

Androgen Antagonists↗

PubMed1998

The Knights of the Round Table hypothesis of tumour suppressor gene function--noble sacrifice or sexual dalliance: genes, including p53, BRCA1/2 and RB have evolved by horizontal and vertical transmission of mating factor genes and are involved in gametogenesis, implantation, development and tumourigenesis.

The genes involved in negative cell cycle regulation and familial tumour susceptibility including APC, BRCA, p53, RB, WT1 are unique and have no homologies with other genes. Our hypothesis suggests they originated from mating factor genes, which halted cell division in response to stress to generate genetic diversity by sexual mechanisms. Some have evolved principally by vertical transmission (mismatch repair), others by horizontal transmission via mobile elements, predominantly in oocytes. We demonstrate amplification in human extra-embryonic tissues in fetus and mother in implantation; in the developing fetus, differing tissue-specific patterns are seen, especially between testis and ovary. We suggest that the fetus is susceptible to maternal transmission of infections including CMV, malaria, trypanosomes, whose sequences occur within these genes. In head and neck cancers, we demonstrate specific patterns of loss or instability involving up to seven different TSG. We suggest mechanisms of tumourigenesis involve transposable elements and episome formation, leading to loss of negative cell cycle regulation and exit from G0.

Animals↗

PubMed1998

Cytogenetic analysis of de novo acute myeloid leukemia with trilineage myelodysplasia in comparison with myelodysplastic syndrome evolving to acute myeloid leukemia.

Characteristics of karyotypes were analyzed in de novo acute myeloid leukemia (AML) with trilineage myelodysplasia (AML/TMDS) at initial diagnosis and compared with myelodysplastic syndrome (MDS) cases that had evolved to AML (MDS/AML). Abnormal karyotypes were seen in 11 of 19 patients with AML/TMDS and 13 of 16 MDS/AML cases. Trisomy 8 was observed in 3 AML/TMDS cases as a sole anomaly and was also present in 3 MDS/AML cases but not as a sole finding. Although MDS/AML frequently displayed monosomies or long-arm deletions of chromosome 5, 7 and 9, only one case exhibited long-arm deletion (of chromosome 7) in AML/TMDS. Two or more chromosome aberrations were found in some cases in both groups. These findings suggest that AML/TMDS had passed through several preleukemic stages at diagnosis, as has been well documented in MDS and MDS/AML. Additionally, clonal evolution may have already occurred in AML/TMDS, as MDS transformed to AML is associated with clonal evolution.

Acute Disease↗

PubMedDate not supplied

Evolving features of lung adenocarcinoma in Rio de Janeiro, Brazil.

Formerly considered rare, adenocarcinoma has become the commonest form of primary lung cancer in developed countries. Its clinical presentation has changed, with central tumors becoming more frequent. We reviewed all biopsies with a diagnosis of primary lung cancer obtained from October 1988 to April 1997 in a tertiary care hospital in Rio de Janeiro. Medical records from adenocarcinomas were analysed. Adenocarcinoma was the commonest form of lung cancer (168/409, 41%). Central tumors were observed in 43% according to radiological criteria and 47% according to bronchoscopic criteria. The frequency and clinical presentation of adenocarcinoma have evolved lately in Rio de Janeiro.

Adenocarcinoma↗

PubMed2000

The evolving role of hormone therapy in advanced prostate cancer.

Earlier diagnosis and treatment of prostate cancer has changed the face of late-stage disease, and the use of mainstay hormonal therapies--orchiectomy, luteinizing hormone releasing-hormone analogs, and combined androgen ablation--are evolving rapidly. New approaches such as antiandrogen monotherapy and intermittent therapy are being evaluated. In addition, palliative treatments for patients with androgen-independent tumors have expanded. The most common clinical presentation of advanced prostate cancer is a rising prostate-specific antigen level following primary therapy (radical prostatectomy or radiotherapy or both). Due to the negative psychological implications of orchiectomy, many patients are opting for treatment with luteinizing hormone-releasing hormone analogs. Because studies of combined androgen ablation have not provided conclusive results, it is reasonable to forego antiandrogen therapy for patients who undergo bilateral orchiectomy. Management options for patients with androgen-independent prostate cancer are expanding and include antiandrogen removal, antiandrogen therapy, and glucocorticoids.

Androgen Antagonists↗

PubMed2001

Comparison of chimpanzee and human leukocyte Ig-like receptor genes reveals framework and rapidly evolving genes.

The leukocyte receptor complex (LRC) on human chromosome 19 contains related Ig superfamily killer cell Ig-like receptor (KIR) and leukocyte Ig-like receptor (LIR) genes. Previously, we discovered much difference in the KIR genes between humans and chimpanzees, primate species estimated to have approximately 98.8% genomic sequence similarity. Here, the common chimpanzee LIR genes are identified, characterized, and compared with their human counterparts. From screening a chimpanzee splenocyte cDNA library, clones corresponding to nine different chimpanzee LIRs were isolated and sequenced. Analysis of genomic DNA from 48 unrelated chimpanzees showed 42 to have all nine LIR genes, and six animals to lack just one of the genes. In structural diversity and functional type, the chimpanzee LIRs cover the range of human LIRs. Although both species have the same number of inhibitory LIRs, humans have more activating receptors, a trend also seen for KIRs. Four chimpanzee LIRs are clearly orthologs of human LIRs. Five other chimpanzee LIRs have paralogous relationships with clusters of human LIRs and have undergone much recombination. Like the human genes, chimpanzee LIR genes appear to be organized into two duplicated blocks, each block containing two orthologous genes. This organization provides a conserved framework within which there are clusters of faster evolving genes. Human and chimpanzee KIR genes have an analogous arrangement. Whereas both KIR and LIR genes can exhibit greater interspecies differences than the genome average, within each species the LIR gene family is more conserved than the KIR gene family.

Animals↗

PubMed2000

Risks of coronary heart disease in women: current understanding and evolving concepts.

The population of older individuals in the United States is growing rapidly. Because women generally live longer than men and make up the majority of this aging population, the elucidation of health issues related to older women is important. Cardiovascular disease is the leading cause of death and disability for women and claims the lives of more women than the next 14 causes combined. The majority of these deaths are due to atherosclerotic coronary heart disease, with nearly 250,000 women dying of myocardial infarction each year. There is evidence that women with suspected or established cardiovascular disease have not benefited fully from recent advances in the detection and management of coronary heart disease. Regardless of the mechanism and extent of the effect that sex differences have on approaches to cardiovascular disease, women appear to benefit from proven efficacious therapies, and the longer-term outcomes associated with these treatments are positive. The data regarding women and coronary heart disease are rapidly evolving and sometimes conflicting. The intent of this article is to summarize the most current understanding of coronary heart disease risks in women, highlighting the impact of prevention, and to discuss the latest novel findings that may become important in our armamentarium for prevention of coronary heart disease.

Adult↗

PubMed2003

Evolving role of the neurologist in the diagnosis and treatment of chronic noncancer pain.

The neurologist has become increasingly involved in the multidisciplinary treatment of patients with chronic noncancer pain (CNP). Chronic noncancer pain affects a diverse patient population with multiple underlying diagnoses and associated therapies. Following the model of the American Board of Anesthesiology and the American Society of Anesthesiologists for practice guidelines and subspecialty requirements, neurologic pain management is now recognized as a subspecialty of neurology by the American Academy of Neurology and the American Board of Psychiatry and Neurology. Current basic and clinical research into the neuropathology, neurophysiology, neurochemistry, and neuropharmacology of chronic pain continues to expand diagnostic and therapeutic options. Informed regulatory agencies and professional organizations such as the American Academy of Neurology recognize the undertreatment of patients with CNP and provide clear recommendations to help neurologists in the ethical and effective treatment of patients with pain. Improved education of neurologists, other health care professionals, patients, and the media about evolving standards of pain care and therapy will produce a more supportive environment for the compassionate and ethical treatment of patients with CNP.

Analgesics, Opioid↗

PubMed2004

Metastasizing and non-metastasizing tumors likely evolve from DNA phenotypes via independent pathways.

We have recently discovered, using statistical models of Fourier transform-infrared spectra, two distinct cancer DNA phenotypes in histologically normal tissues surrounding non-metastasizing primary tumors and tumors with evidence of distant metastases. Structural comparisons of the DNA from these tumor types imply that each evolves via a separate pathway from DNA phenotypes originating in progenitor cells. These findings challenge the widely-held concept of metastasis.

Animals↗

PubMed1990

Evolving educational practices in occupational therapy: the War Emergency Courses, 1936-1954.

The paper uses evidence collected from both written and oral history sources to present one approach to understanding the way in which educational practices evolved in occupational therapy. The paper introduces two fundamental positions regarding the nature, scope, and content of professional preparation for occupational therapists. For expediency, these viewpoints are labeled academicism and experientialism. This paper traces the interaction of these positions in the development and implementation of the War Emergency Courses. The implications for educational policy in occupational therapy arising from that program are also examined.

Curriculum↗

PubMed1998

Evolving competence in the practitioner role.

This article discusses competence from the viewpoint of the practitioner role. Concepts from two documents published by the American Occupational Therapy Association--Occupational Therapy Roles and Developing, Maintaining, and Updating Competency in Occupational Therapy: A Guide to Self-Appraisal--are integrated within the discussion. Discussed in this article are factors that affect competence, the interrelationship of competence and practice, and personal responsibility for competence; ways in which competence may be challenged during the practitioner's career; common misconceptions about competence; and attitudes and actions in which the competent practitioner engages. Competence is described as a complex and evolving set of abilities that develops throughout the practitioner's career.

Clinical Competence↗

PubMed2006

The nurse academic in the clinical learning setting: an evolving partnership role.

Student readiness for practice as a registered nurse can only be achieved through a committed and cooperative partnership between the tertiary and clinical sectors. One important role in the development and maintenance of clinical learning partnerships is that of the nurse academic. As nursing faculties continue to evolve this role it is important that positive initiatives be shared and challenges discussed. With this in mind, the role of the nurse academic in clinical practice introduced at the University of Technology, Sydney (UTS) will be presented. A nurse academic who fulfils this role at UTS is known as an Academic Liaison Person (ALP). This paper begins with a general exploration of the role of the academic in the clinical learning setting and then discusses the associated challenges. The role of the ALP at UTS and its integration with the UTS clinical model for final year students will be presented as a response to these challenges. Through this model the educational expertise of the ALP and the clinical expertise of the practitioner is brought together for the benefit of the nursing student.

Adaptation, Psychological↗

PubMed1988

Hepatic candidiasis in cancer patients: the evolving picture of the syndrome.

Focal hepatosplenic candidiasis has been recognized with increasing frequency in recent years. We reviewed the cases of eight patients seen between 1982 and 1985, and information on 60 patients whose cases have been reported in the world literature. The characteristics of focal hepatosplenic candidiasis include persistent fever in a neutropenic patient whose leukocyte count is returning to normal, often coupled with abdominal pain; an elevated alkaline phosphatase level; and less commonly, rebound leukocytosis. The characteristic "bull's eye" lesions seen with hepatic ultrasound examination or computed tomography generally are not detectable until neutrophil recovery has occurred. Diagnosis can be established only by biopsy evidence of yeasts or pseudohyphae in the granulomatous lesions. Cultures are frequently negative, however, especially in patients who have been pretreated with antifungal agents. We review the evolving nature of hepatosplenic candidiasis, focusing on diagnosis and treatment.

Adolescent↗

PubMed2001

Evolving indications for permanent pacemakers.

New indications for permanent cardiac pacing have been developed in recent years, with numerous studies demonstrating improved clinical outcomes in a variety of disorders. Because hypertrophic obstructive cardiomyopathy, dilated cardiomyopathy, heart failure, neurocardiogenic syncope, and atrial fibrillation are common conditions, every clinician should be aware of evolving alternative therapies for them. Observational studies in patients with refractory, symptomatic hypertrophic obstructive cardiomyopathy and significant left ventricular outflow gradient at rest suggest that cardiac pacing may result in symptomatic and hemodynamic improvement. Clinical trials have not shown conclusive evidence regarding the long-term benefit from pacing in these patients, and it is unclear whether pacing will be a preferred treatment option. Preliminary data suggest that pacing is a viable adjunctive therapeutic approach for improving symptoms in patients with dilated cardiomyopathy and heart failure. Mortality benefit has yet to be established, but it is to be hoped that ongoing randomized clinical trials will provide definitive information on that issue. Patients with refractory neurocardiogenic syncope or those who are intolerant of medical treatment may benefit from pacing therapies, especially those that use rate-drop sensor algorithms. Biatrial pacing has emerged as a technique that resynchronizes atrial electrical activity and has been shown to prevent atrial fibrillation. Multisite atrial pacing for the prevention of atrial fibrillation is considered investigational but seems promising. Newer indications for pacing are expected to result in improved clinical outcomes for hypertrophic obstructive cardiomyopathy, dilated cardiomyopathy and heart failure, neurocardiogenic syncope, and the prevention of atrial fibrillation.

Atrial Fibrillation↗

PubMed2001

Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.

Idiopathic pulmonary fibrosis is a progressive and usually fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling, which result in irreversible distortion of the lung's architecture. Although the pathogenetic mechanisms remain to be determined, the prevailing hypothesis holds that fibrosis is preceded and provoked by a chronic inflammatory process that injures the lung and modulates lung fibrogenesis, leading to the end-stage fibrotic scar. However, there is little evidence that inflammation is prominent in early disease, and it is unclear whether inflammation is relevant to the development of the fibrotic process. Evidence suggests that inflammation does not play a pivotal role. Inflammation is not a prominent histopathologic finding, and epithelial injury in the absence of ongoing inflammation is sufficient to stimulate the development of fibrosis. In addition, the inflammatory response to a lung fibrogenic insult is not necessarily related to the fibrotic response. Clinical measurements of inflammation fail to correlate with stage or outcome, and potent anti-inflammatory therapy does not improve outcome. This review presents a growing body of evidence suggesting that idiopathic pulmonary fibrosis involves abnormal wound healing in response to multiple, microscopic sites of ongoing alveolar epithelial injury and activation associated with the formation of patchy fibroblast-myofibroblast foci, which evolve to fibrosis. Progress in understanding the fibrogenic mechanisms in the lung is likely to yield more effective therapies.

Anti-Inflammatory Agents↗

PubMed1990

Ultrasound of the septum pellucidum. Recognition of evolving fenestrations in the hydrocephalic infant.

Fenestrations of the septum pellucidum may be noted in hydrocephalic infants. This finding and its changing image was noted in six premature infants evaluated by neurosonography over time periods ranging from weeks to months. Breaks in the septum were noted to occur from 14 days to 23 weeks after the sonographic diagnosis of hydrocephalus. Some of these fenestrations were noted to increase in size and/or become bilateral over time. The awareness of evolving fenestrations and their late-stage images helps avoid confusion with partial and complete agenesis of the septum pellucidum and their possible associated neuroanatomical abnormalities.

Cerebral Hemorrhage↗

PubMed2002

The evolving appearance of a congenital diaphragmatic hernia.

OBJECTIVE: The prenatal differentiation of a fetal congenital diaphragmatic hernia from other echogenic chest masses can be difficult. The implications of the leading diagnosis can greatly affect the neonatal prognosis. The cases presented illustrate how the primary diagnosis of a fetal chest mass can change during the course of gestation as the appearance of the chest mass evolves. METHODS: A descriptive analysis of 2 cases reviewed the importance of considering multiple causes of an echogenic chest mass. RESULTS: The sonographic features of a congenital diaphragmatic hernia that have been described in the literature were not always present at the time of initial evaluation. CONCLUSIONS: A congenital diaphragmatic hernia should be part of the differential diagnosis considered during consultation with parents whose fetus has an echogenic chest mass.

Adult↗

PubMed1994

The evolving role of the primary care physician.

In today's climate of health care reform, the title of this article might more appropriately be "Is the Role of the Primary Care Physician Evolving or Going the Way of the Dinosaur?" According to Koop, primary care is in trouble. Whereas only 29 percent of U.S. physicians are primary care physicians, in Great Britain, 72 percent of physicians are primary care physicians and in Europe and Canada the average is 50 percent. Many U.S. primary care physicians are in the later stages of their careers and nearing retirement age. Unless the supply increases, this number will dwindle further. However, in 1992, only 14 percent of U.S. medical school graduates were headed for primary care careers. Even if the supply of primary care graduates were increased to 50 percent of the graduating medical school class, it would be well into the next century before the ratio of primary care physicians to specialists would be equal. Primary care is at a critical juncture and the next few years will decide the fate of the primary care physician. Given the state of primary care today, I believe that a fundamental look at the assumptions regarding the role of primary care physicians is in order. The current health reform movement has placed a major responsibility on primary care to solve many of the problems in health care delivery today, such as cost, utilization, and prevention. Many health care organizations are planning strategies involving primary care providers, and physician executives can play a key role in these decisions.

Physician's Role↗