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At least 325 records · Page 18Linked to original sources
PubMed2005

Inhibition of phosphatidylinositol 3-kinase sensitizes ovarian cancer cells to carboplatin and allows adjunct chemotherapy treatment.

Signal transduction pathways associated with cancer progression and chemotherapeutic resistance are being investigated as molecular targets for chemotherapy. The phosphatidylinositol 3-kinase (PI3K) pathway has been found to be frequently amplified and have increased activity in ovarian cancer. The current study investigates the efficacy of an antagonist of PI3K, LY294002, in inhibiting ovarian cancer cell growth and survival both in vitro and in vivo. The hypothesis tested is that inhibition of PI3K signaling makes ovarian cancer cells susceptible to the effects of platinum-based chemotherapy. Observations show that LY294002 is an effective inhibitor of ovarian cancer cell growth and survival in vitro. Inhibition of PI3K/Akt signaling increased the sensitivity of ovarian cell cultures to the cytotoxic effects of carboplatin. The combined treatment of LY294002 and carboplatin was needed to optimally promote cellular apoptosis and decrease ovarian cancer cell survival in vitro. To extend these observations, a model involving in vivo i.p. growth of human ovarian tumors in a nude mouse was used. LY294002 in combination with carboplatin was more effective in inhibiting ovarian cancer cell xenograft growth than either agent alone. The results of this study suggest that the combined treatment of carboplatin and LY294002 can effectively decrease ovarian tumor progression and support the use of a PI3K inhibitor (e.g., LY294002) as an adjunct platinum-based drug therapy for treatment of ovarian cancer.

Animals↗
PubMedDate not supplied

A new paradigm of T cell allergy: requirement for the B-1 cell subset.

BACKGROUND: We have uncovered a role for B-1-B-cell-produced IgM antibody, in the initiation of contact sensitivity (CS) in mice. CS and delayed-type hypersensitivity (DTH) involve recruitment of T cells to the tissues, to be activated by antigen-presenting cells (APC), and then make cytokines. Little is known about low recruitment is initiated. In CS, soon after immunization, the unique B-1 cell subset, responsible for the formation of most IgM, is activated to produce antigen (Ag)-specific IgM for export to tissues. IgM forms complexes with challenge Ag, activating the classical complement (C) pathway, generating C5a, to activate endothelium directly, or indirectly via C5a receptors (R) on mast cells and platelets, that release vasoactive amines (serotonin) and cytokines (TNF-alpha). These act together to induce vasodilatation, vascular permeability and expression of endothelial adhesion molecules to promote optimal T cell recruitment. METHODS AND RESULTS: New findings that established this pathway include: (1) absent CS response in C-deficient, or C-inhibited mice; (2) local generation of C5a in CS tissue extracts; (3) absent CS in C5aR-/- mice; (4) decreased CS in B cell and B-1-cell-deficient mice, and (5) reconstitution of CS by transfer of B-1 cells, or hapten-specific IgM. CONCLUSION: These findings indicate that the B-1 subset producing Ag-specific IgM is required early in CS to activate C, to induce vasoactive mediators that initiate local T recruitment.

Animals↗
PubMedDate not supplied

Quality assurance and risk reduction guidelines.

Cervical cancer continues to be a major cause of death in women worldwide. The major problem facing most women is the unavailability of screening Pap tests in poor and underdeveloped countries. While rates of cancer deaths have decreased 60-80% in developed countries since the Pap test became available, the accuracy of Paps was challenged recently. In order to instill public confidence and promote optimal patient care, measures to improve the quality of the entire screening process should be undertaken. Continuous quality improvement processes are more appropriate than traditional quality assurance monitors. Although no standards can be defined that are applicable to all laboratory settings and nations, this document provides current views on universal quality procedures and risk reduction. Procedure/policy manuals, workload assessment, hierarchic/peer review, discrepancy analysis, rescreening studies and cytohistologic correlation are examples of universally applicable quality tools. The variability in practices in different parts of the world is also discussed.

Female↗
PubMed1981

Relaxation properties of mammalian atrial muscle.

The properties of relaxation, particular the sensitivity of relaxation to load, were analyzed in isolated intact atrial muscle and in manually dissected, detergent-treated cellular preparations from cat, dog, and rat atria. Force and length traces under increasing afterloads and following load clamps were obtained using an electromagnetic lever-force transducer system for the intact muscles and a capacitance transducer system for the cellular preparations. In both types of preparations, the time course of relaxation was hardly affected by the load or by alterations in load (load clamps), unlike intact mammalian ventricular muscle. This load independence of relaxation, which was hardly influenced by variations of initial muscle length, resembled relaxation in intact frog ventricular muscle and in detergent-treated mammalian ventricular single cells. As relaxation of these ventricular preparations with poorly developed (frog) or absent (detergent-treated single cells) calcium-sequestering systems was shown to be governed by the dissipation of activation, these results suggest a similar control mechanism for relaxation in mammalian atrial muscle. Furthermore, load independence of relaxation of mammalian atrial muscle in late diastole may promote optimal filling of the ventricle.

Animals↗
PubMed1977

Influence of a deficiency of the second component of complement on the bactericidal activity of neutrophils in vitro.

Serum from three patients with a complete, selective deficiency of the second component of complement (C2) did not promote optimal killing of Staphylococcus aureus, 502A by neutrophilic polymorphonuclear leukocytes (PMN) in vitro. The addition of C2 reagent or the presence of heat-stable opsonin in the C2-deficient serum corrected the defective killing of S. aureus that was observed with patient or control PMN. PMN from the patients or control subjects killed bacteria with equal efficiency under conditions of optimal opsonization (normal pooled serum). However, twice-washed control PMN were better than patient PMN in killing S. aureus under circumstances of suboptimal opsonization (C2-deficient serum, heated C2-deficient serum, heated normal pooled serum, or no replacement of serum). The latter finding was due to residual C2 on the surface of twice-washed control cells. As repeated washing of control PMN progressively removed cell-associated C2, the staphylocidal effectiveness of the control RMN decreased to the level of patient PMN. In contrast to the findings with S. aureus, triply-washed PMN from patients or controls killed normal numbers of Escherichia coli, ON2, in C2-deficient serum.

Animals↗
PubMed2001

Requirements for multidisciplinary teamwork in psychiatric rehabilitation.

Psychiatric rehabilitation by its very nature is multidisciplinary because of the many competencies required for its implementation. In promoting optimal levels of recovery from schizophrenia and other disabling mental disorders, teams must combine the expert contributions of professionals and paraprofessionals who can individualize a comprehensive array of evidence-based services with competency, consistency, continuity, coordination, collaboration, and fidelity. The authors describe the properties and functions of the multidisciplinary team and key attributes of effective teams. The importance of teams' involving clients, their relatives, and other supporters in setting personally relevant life goals is emphasized. The authors provide examples of the challenges posed by the need to individualize services and of the ways in which barriers to communication and coordination can be overcome. The roles of the various team members are described, including leadership roles and the unique role of the psychiatrist, in the context of newly emerging, evidence-based treatments for psychiatric rehabilitation.

Case Management↗
PubMed1975

Dependence and psychotherapy--developmental considerations.

This article illustrates how the assessment of the level and degree of dependency in psychotherapy can be used as a diagnostic and therapeutic tool. Dependency varies with the stage of psychosexual development, with the degree and state of illness, and with the stage of treatment. Appropriate monitoring of this factor promotes optimal growth potential in the patient.

Affective Symptoms↗
PubMed2004

Occupational performance challenges for children with congenital heart disease: a literature review.

BACKGROUND: Paediatric specialists have advocated for exercise training programs for children with congenital heart disease without addressing other common deficits, such as behavioural and psychological problems. Despite evidence of the role of occupational therapy in rehabilitation for adults with cardiac disease, there has been little published about occupational therapy for children with congenital heart disease. PURPOSE: This literature review on the outcomes of congenital heart disease, guided by the Canadian Model of Occupational Performance, highlights the comprehensive needs of these children. RESULTS: The findings of the review are that congenital heart disease can have wide-ranging neurological and psychosocial implications. This suggests that occupational therapists should be concerned about limitations in the participation of these children in age-appropriate childhood occupations related to self-care, productivity or leisure. PRACTICE IMPLICATIONS: As cardiac rehabilitation program planning becomes more commonplace for children, comprehensive programs that promote optimal occupational performance need to be developed, implemented and evaluated.

Activities of Daily Living↗
PubMed2005

The use of parenteral nutrition in a severely malnourished hemodialysis patient with hypercalcemia.

There is a high prevalence of protein-energy malnutrition (PEM) in chronic dialysis patients. Causes of PEM include the catabolic effects of hemodialysis treatments, acidemia associated with end-stage renal disease, common comorbid conditions, and uremia-induced anorexia. Morbidity and mortality increase with PEM. Before considering parenteral nutrition (PN) as a nutrition intervention in a maintenance dialysis patient, all other efforts to promote optimal nutrition need to be exhausted. The first step is careful evaluation of protein-energy status, followed by intensive nutrition counseling. If necessary, this is followed by oral nutrition supplementation, appetite stimulation, enteral tube feedings, and finally PN. Short-term parenteral nutrition (PN) became a crucial component of the management of a 38-year-old hemodialysis (HD) patient who endured serious complications after kidney transplant rejection. A profound and prolonged malnourished state followed her treatment for necrotizing pancreatitis. She had developed persistent hypercalcemia believed secondary to tertiary hyperparathyroidism (HPT) and immobilization. Later, she developed hungry bone syndrome (HBS) after parathyroidectomy (PTX). She also developed refeeding syndrome after initiation of PN. The patient's persistent, poorly understood hypercalcemia did not resolve even after PTX and removal of all other sources of vitamin D and calcium from her feedings, medications, and dialysis bath. The close communication of the inpatient and outpatient dialysis multidisciplinary teams became a key component to the successful outcome in this complex patient.

Adult↗
PubMedDate not supplied

What is the future of diabetic wound care?

With diabetes affecting 5% to 10% of the US population, development of a more effective treatment for chronic diabetic wounds is imperative. Clinically, the current treatment in topical wound management includes debridement, topical antibiotics, and a state-of-the-art topical dressing. State-of-the-art dressings are a multi-layer system that can include a collagen cellulose substrate, neonatal foreskin fibroblasts, growth factor containing cream, and a silicone sheet covering for moisture control. Wound healing time can be up to 20 weeks. The future of diabetic wound healing lies in the development of more effective artificial "smart" matrix skin substitutes. This review article will highlight the need for novel smart matrix therapies. These smart matrices will release a multitude of growth factors, cytokines, and bioactive peptide fragments in a temporally and spatially specific, event-driven manner. This timed and focal release of cytokines, enzymes, and pharmacological agents should promote optimal tissue regeneration and repair of full-thickness wounds. Development of these kinds of therapies will require multidisciplinary translational research teams. This review article outlines how current advances in proteomics and genomics can be incorporated into a multidisciplinary translational research approach for developing novel smart matrix dressings for ulcer treatment. With the recognition that the research approach will require both time and money, the best treatment approach is the prevention of diabetic ulcers through better foot care, education, and glycemic control.

Diabetes Complications↗
PubMed2002

Companion animals and adaptation in chronically ill children.

Almost 20 million children in the U.S. have a chronic illness. Chronic illness requires ongoing management in the home, often with complex, stressful regimens. The increased lifespan of chronically ill children may lead to increased long term psychosocial and physical sequelae. Enhancing the quality of life for these children could promote optimal long-term adaptation. Health benefits of companion animals have been described across psychosocial, physiological. and behavioral spheres for healthy children and children with disabilities. These benefits have not been empirically examined for chronically ill children. This paper uses a stress-coping model to examine the role animals may play in adaptation for children with chronic illnesses. The contribution of companion animals to the constructs within the model and the adaptation process is discussed. This model provides a potential theoretical framework for synthesizing literature and pursuing empirical work on the role of companion animals in chronic childhood illness.

Adaptation, Psychological↗
PubMed1997

Enteral nutrition for the burn patient.

In summary, thermal injury elicits numerous pathophysiological aberrations that affect nutritional status. The current recommendation for macronutrient provision postburn supports a high-calorie, protein and carbohydrate regimen and a reduction of the fat provision because of its apparent immunosuppressive properties. Early and continuous enteral feeding in the burn patient promotes optimal conditions for wound healing and immunocompetence. Because of its direct effect on morbidity and mortality, the introduction of early, continuous enteral feedings is recommended as standard therapy after burn injury. Finally, monitors for enteral placement and tolerance should be incorporated into routine care as well as the multidisciplinary Quality Management Program.

Burns↗
PubMedDate not supplied

Integrating the child into home and community following the completion of cancer treatment.

The present article examines the period of time immediately following the completion of treatment for childhood cancer. The unique concerns experienced by families at this stage of the cancer treatment are examined, and the specific challenges that children face as they renegotiate roles and relationships that are necessary for successful reintegration into family, school, and community settings are discussed. Obstacles to successful reintegration that are frequently encountered by patients and families are reviewed, as well as variables that may promote optimal adjustment during this transitional period. The need for continued research in this area is highlighted, and specific research questions are identified. An emphasis is placed on applying a socioecological framework to research and clinical work with pediatric oncology patients at this stage of the cancer experience.

Adaptation, Psychological↗
PubMed2002

Reconciling incompatibilities: a grounded theory of HIV medication adherence and symptom management.

The purpose of this grounded theory study was to explain how ethnically diverse men and women living with HIV manage their interacting illness symptoms, medication side effects, and treatment adherence choices. The authors used the constant comparative method to analyze textual data from in-depth interviews with 66 HIV-infected people representing the changing HIV demographic profile in the San Francisco Bay area and generate a theory of Reconciling Incompatibilities. Adherence options of complying, not complying, or self-tailoring occurred in a context of attributional uncertainty as to whether distress was illness- or treatment-related, a sometimes silent virus, and perceived fickle medical markers. Conditions, including self-identity, illness ideology, concurrent treatment regimens, the meaning of time, medication burden and side effects, and lifestyle, coalesced to produce a state of mind that shaped adherence choices on a dose-by-dose basis. This theory offers a basis for interventions designed to promote optimal adherence choices concerning HIV therapies.

Adult↗
PubMed2006

Differences in parenting needs of fathers of children with chronic conditions related to family income.

Children with chronic conditions now survive longer than has been true historically, creating a need to promote optimal growth and development for themselves, their family members and the family as a whole. This article reporting a midwestern United States study compares the concerns and coping strategies of fathers of chronically-ill children with household annual incomes less than $50,000 with fathers of chronically-ill children with household incomes of $50,000 or more. The sample of 48 fathers completed the Hymovich Family Perception Inventory anonymously. The results revealed differences in the parenting concerns of fathers related to family income. The low-income fathers expressed a desire for more knowledge about the children's condition and worries about family finances. Professional anticipatory guidance and dissemination of information holds promise for providing the support needed by fathers of children with chronic conditions, particularly those with lower household incomes.

Adaptation, Psychological↗
PubMed2003

Comparison of recombinant human luteinising hormone (r-hLH) and human menopausal gonadotropin (hMG) in assisted reproductive technology.

Follicle-stimulating hormone (FSH) and luteinising hormone (LH) act in concert in the stimulation of folliculogenesis and ovulation. However, high levels of LH promote follicular atresia and early miscarriage, and this has led to the concept of a 'therapeutic window' of LH for successful conception in assisted reproductive technology (ART) and ovulation induction. Until now, urinary-derived human menopausal gonadotropin (hMG) has been the only available source of exogenous LH activity. hMG preparations contain highly variable levels of LH, and are often augmented with human chorionic gonadotropin (hCG), which mimics LH activity. Accumulation of hCG bioactivity, however, may have detrimental effects on follicular development and oocyte quality. Recombinant human LH (r-hLH) (Luveris) is the only pure source of LH activity. r-hLH is well characterised and production is tightly controlled, resulting in a highly consistent product. Clinical studies in hypogonadotropic hypogonadal women have demonstrated the efficacy of r-hLH, 75 IU/day, together with r-hFSH, 150 IU/day, in promoting optimal follicular development, oestrogen secretion and endometrial thickness. r-hLH therefore provides the clinician with the opportunity for precise and consistent dosing within the therapeutic window for patients requiring exogenous LH, without the risk of LH overexposure that is associated with hCG.

Dose-Response Relationship, Drug↗
PubMed2006

Evaluating the quality of interaction between medical students and nurses in a large teaching hospital.

BACKGROUND: Effective health care depends on multidisciplinary collaboration and teamwork, yet little is known about how well medical students and nurses interact in the hospital environment, where physicians-in-training acquire their first experiences as members of the health care team. The objective of this study was to evaluate the quality of interaction between third-year medical students and nurses during clinical rotations. METHODS: We surveyed 268 Indiana University medical students and 175 nurses who worked at Indiana University Hospital, the School's chief clinical training site. The students had just completed their third year of training. The survey instrument consisted of 7 items that measured "relational coordination" among members of the health care team, and 9 items that measured psychological distress. RESULTS: Sixty-eight medical students (25.4%) and 99 nurses (56.6%) completed the survey. The relational coordination score (ranked 1 to 5, low to high), which provides an overall measure of interaction quality, showed that medical students interacted with residents the best (4.16) and with nurses the worst (2.98; p < 0.01). Conversely, nurses interacted with other nurses the best (4.36) and with medical students the worst (2.68; p < 0.01). Regarding measures of psychological distress (ranked 0 to 4, low to high), the interpersonal sensitivity score of medical students (1.56) was significantly greater than that of nurses (1.03; p < 0.01), whereas the hostility score of nurses (0.59) was significantly greater than that of medical students (0.39; p < 0.01). CONCLUSION: The quality of interaction between medical students and nurses during third-year clinical rotations is poor, which suggests that medical students are not receiving the sorts of educational experiences that promote optimal physician-nurse collaboration. Medical students and nurses experience different levels of psychological distress, which may adversely impact the quality of their interaction.

Adult↗
PubMed2005

The association between clinical integration of care and transfer of veterans with acute coronary syndromes from primary care VHA hospitals.

BACKGROUND: Few studies report on the effect of organizational factors facilitating transfer between primary and tertiary care hospitals either within an integrated health care system or outside it. In this paper, we report on the relationship between degree of clinical integration of cardiology services and transfer rates of acute coronary syndrome (ACS) patients from primary to tertiary hospitals within and outside the Veterans Health Administration (VHA) system. METHODS: Prospective cohort study. Transfer rates were obtained for all patients with ACS diagnoses admitted to 12 primary VHA hospitals between 1998 and 1999. Binary variables measuring clinical integration were constructed for each primary VHA hospital reflecting: presence of on-site VHA cardiologist; referral coordinator at the associated tertiary VHA hospital; and/or referral coordinator at the primary VHA hospital. We assessed the association between the integration variables and overall transfer from primary to tertiary hospitals, using random effects logistic regression, controlling for clustering at two levels and adjusting for patient characteristics. RESULTS: Three of twelve hospitals had a VHA cardiologist on site, six had a referral coordinator at the tertiary VHA hospital, and four had a referral coordinator at the primary hospital. Presence of a VHA staff cardiologist on site and a referral coordinator at the tertiary VHA hospital decreased the likelihood of any transfer (OR 0.45, 95% CI 0.27-0.77, and 0.46, p = 0.002, CI 0.27-0.78). Conversely, having a referral coordinator at the primary VHA hospital increased the likelihood of transfer (OR 6.28, CI 2.92-13.48). CONCLUSIONS: Elements of clinical integration are associated with transfer, an important process in the care of ACS patients. In promoting optimal patient care, clinical integration factors should be considered in addition to patient characteristics.

Acute Disease↗