Mutant clones in normal epithelium outcompete and eliminate emerging tumours.

Human epithelial tissues accumulate cancer-driver mutations with age1-9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10-12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours11-14. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.

Requirements for muscle relaxants during radical retropubic prostatectomy.

BACKGROUND: The need for the routine use of muscle relaxants to provide an adequate surgical field for intraabdominal surgery has not been established. This study tested the hypothesis that vecuronium decreases the frequency of unacceptable operating conditions for patients undergoing radical retropubic prostatectomy who are anesthetized with isoflurane and fentanyl. METHODS: After obtaining informed consent, patients in this blinded, placebo-controlled study were randomized to receive either an infusion of vecuronium or saline (placebo) beginning 5 min after fascial incision during the maintenance of anesthesia with at least 1 minimum alveolar concentration end-tidal isoflurane and fentanyl infusion. The surgical field was graded from 1 (excellent) to 4 (unacceptable) by the surgeons at 15-min intervals. If a grade 4 rating occurred (defined as a treatment failure), the patient received rescue vecuronium. RESULTS: A total of 120 patients are included in this report (59 in the vecuronium group and 61 in the placebo group). The frequency of treatment failure in the placebo group was 17 of 61 (27.9%) versus 1 of 59 (1.7%) in the control group who received vecuronium (P < 0.001). Thirty-eight patients (62.3%) in the placebo group and 52 patients (88.1%) in the vecuronium group had surgical field ratings of < or = 2 (good to excellent) at each time assessed throughout the procedure. CONCLUSION: The study hypothesis was confirmed. However, an isoflurane-fentanyl anesthetic alone produced a good to excellent surgical field in approximately two thirds of patients undergoing radical retropubic prostatectomy without the use of muscle relaxants. Thus, the routine use of muscle relaxants in adequately anesthetized patients undergoing this procedure may not be indicated.

Patterns of spirituality in persons with advanced HIV disease.

This study was conducted to explicate the role of spirituality in dealing with the many struggles of advanced HIV disease. The research question that guided the study was: How is spiritual meaning structured in advanced stages of HIV disease? Published articles have lacked sound conceptions of spirituality that would allow it to be described apart from religion as a concept within humanistic science. Qualitative methodological assumptions were derived from interpretive interactionism. The spiritual experiences of 10 men and women in advanced-stage (symptomatic) HIV disease who self-identified that they had either spiritual or religious experiences that had helped them cope with HIV disease were interpreted. Data were collapsed, over three iterations, into three major themes to build the meaning of spirituality in HIV. Extracted themes were: purpose in life emerges from stigmatization; opportunities for meaning arise from a disease without a cure; and after suffering, spirituality frames the life.

Spirituality in terminal illness. An alternative view of theory.

I use data and insights gained from 10 years of research and practice on psychosocial and spiritual aspects of living with HIV to outline a critique of extant knowledge on spirituality and to propose an alternative. Nurses are in an excellent position to experience the human spirit. We can use the resultant understandings to be present with others and to become more self-aware and self-loving. I present here my philosophy and personal rules for understanding the spirit that were taught to me by patients and knowledgeable research participants as they helped me to see how my professional objectivity and application of professional knowledge were anathema to their self-discovery. I present a critique of some of the confining aspects of nursing theory, particularly that which is built on developmental frameworks to show how our vision is skewed negatively by these frameworks, and how it may cause us to look down at patients rather than at them as equals.

The psychiatric model: a critical analysis of its undermining effects on nursing in chronic mental illness.

Nursing has incorporated many aspects of the medical model in forming nursing practice. I argue that this conception has not resulted in an effective approach for patients with mental illness, especially those with chronic mental illness. In attempting to formulate practice, nurses are impeded by the constraints of this almost universally accepted model, perhaps in ways that have evaded conscious awareness. Patients, also, must try to live their lives within limited options imposed by professional people who supposedly have their best interest at heart. This article identifies the assumptions of the psychiatric medical model and shows how using this narrow, received format is inconsistent with nursing practice. The author delineates the process of her awakening to its undermining effect on her relationships with patients and offers suggestions for more appropriate practice in chronic mental illness.

Technical and practical considerations involved in operations on patients weighing more than 270 kg.

Care of the patient with superobesity requires special precautions and appropriate equipment. Recently, we performed bariatric procedures (modified very-long-limb Rouxen-Y gastric bypass) on patients weighing 355 kg and 377 kg. These procedures required preoperative preparation concerning safe means of transport of the patient, techniques of anesthesia and intraoperative exposure, provisions for postoperative recovery, and measures to assure patient comfort and hygiene postoperatively. In addition to specially designed bariatric procedures for the superobese, specialized equipment is needed to protect the health of the patient and the staff. All health care providers and especially acute care centers must have preconceived protocols to treat the superobese patient. In addition, specialized equipment is necessary to allow safe transport and support of these patients.

Ways of maintaining hope in HIV disease.

Utilizing Denzin's interpretative interactionism, this study was focused on the experiences of eight men and two women who were in Clinical Category C (AIDS) of HIV Disease. Interviews and analysis revealed their interpretations of the illness and the ways that they maintained hope while coping with end-stage HIV. There were four major ways that hope was maintained: by miracles, religion, involvement in work or vocations, and support of family and friends. These themes are discussed as they relate to the context of HIV within the structure of biomedicine.

Self in relation: a prolegomenon for holistic nursing.

We have outlined some of the characteristics of holistic nursing and have named and explored the concepts that we believe are important to holistic practice. We have outlined assumptions that offer to nursing a more caring and connected way of interacting with clients than currently exists in nursing practice. We do not have answers to the questions of how to implement this practice within the structure of current nursing practice. Occasionally when we discuss these ideas with other nurses, they tell us that nursing as currently practiced in hospitals and community agencies is just the "real world," as though we had better get used to it. Maybe the world that we have presented is the "unreal world," for the moment at least. We are proud to live and learn in this unreal world and in a community of folks who make their living in holistic practice. If we had to make our living working in the "real world" of health care, could we do something to change it before the conflicts drove us away? The concluding question is, "Will nurses use their joint power to build therapeutic environments within nursing, or must they defect from nursing to practice holistic care?"

Postmenopausal endometrioma and hormonal replacement therapy.

This case of postmenopausal endometrioma following hormonal replacement therapy (HRT) demonstrates the often forgotten possibility of reactivation of endometriosis with HRT. The diagnosis of endometriosis should be considered in a postmenopausal woman who presents with pelvic pain and mass whilst on HRT.

Overcoming stigmatization: social and personal implications of the human immunodeficiency virus diagnosis.

All diseases have attached metaphors. Social and personal reactions to people with human immunodeficiency virus are influenced by the metaphor, "fear of polluting people," and have in common with sexually transmitted diseases, the irrational fear of easy contagion. These issues negatively affect clients' response to their diagnosis and their treatment and care. Many clients have suffered as a result of receiving care from professionals who are condemning of the person with the disease. Others, though have found supportive care givers and have experienced positive reactions to the diagnosis through achieving emotional and spiritual development. The response of nursing to this stigmatized disease is explicated.

The struggle of the diagnosed terminally ill person to maintain hope.

Clinical, empirical, and subjective data are used to explore the concept of hope as it is lived by persons who are diagnosed as terminally ill. Interviews with 11 men who were in stage 2 (asymptomatic) HIV disease explicate the form that hope takes and its role in promoting health when a person must cope with a serious diagnosis. Other research and ideas about hope and dying are presented and a critique is presented of both these ideas and current nursing practice.

Challenging the focus on technology: a critique of the medical model in a changing health care system.

The medical model and medical technology have had a pervasive effect on society. Their importance to nursing and to nursing's clients cannot be overstated. This article explores the belief system of medicine and challenges its "germ theory" conceptual underpinnings. Other issues explored are the lack of established efficacy of practice stemming from the medical model; the attendant but unaddressed ethical and iatrogenic questions; the model's destructive effect on health and well-being; and, finally, the economic consequences of the medical model for consumers and the practice of other professional groups. Nurses are urged to consider paradigms that derive from ecological and process orientations to support nursing's concern with health and quality of life.