PubMed HealthSearch

Biomedical subjects

M Grant

Publications and source records attributed to M Grant.

At least 19 recordsLinked to original sources

Measurement of quality of life in bone marrow transplantation survivors.

This study was designed to assess the reliability and validity of a Quality of Life (QOL) instrument on a sample of 179 allogeneic Bone Marrow Transplant (BMT) survivors. The QOL-BMT tool was developed specifically for this population and was based on the investigators' prior research and a conceptual model of Quality of Life. Patients who were at least 100 days post BMT completed the 30 item visual analogue questionnaire. The instrument measured physical symptoms (e.g., weight loss, frequent colds, skin changes, cataracts, sexual problems), psychological symptoms (e.g., worry about recurrence, adjustment to illness), social concerns (e.g., relationship adjustment, return to work), and spiritual well-being (e.g., sense of control, future goals). Psychometric analysis of the instrument included measures of reliability and validity. The study findings demonstrate the unique aspects of QOL dimensions in BMT survivors and the value of QOL assessment in clinical practice and research.

Adaptation, Psychological

Studies on the immediate and delayed leucocytosis elicited by brief (30-min) strenuous exercise.

Eight healthy male volunteers exercised for two 30-min sessions starting 3 h apart on an electronically braked cycle ergometer at a work load (mean 155.9 W, SD 33.4 W) which required an oxygen consumption that was 70% of their maximal rate of oxygen uptake. Venous blood samples were taken through an indwelling cannula over a period of 6 h beginning shortly before the first bout of exercise and were analysed for routine haematological parameters and for lactate, noradrenaline, adrenaline and cortisol. Both bouts of exercise induced an immediate leucocytosis due to rises in lymphocytes and neutrophils but only the first exercise bout induced a substantial delayed neutrophilia. In at least five subjects, changes in lymphocyte and platelet numbers were correlated (Spearman's rank procedure, P less than 0.05) with simultaneous changes in the plasma concentrations of lactate, noradrenaline and adrenaline over the 6-h period studied. Increases in the plasma concentration of cortisol due to exercise correlated positively with the percentage changes in neutrophil numbers at 3 h and 6 h. These results are consistent with the suggestion that the immediate and delayed leucocytosis induced by exercise are mediated respectively by catecholamine and by cortisol.

Adult

Tolerance to the effects of ethanol on the speed and success of reaction time responding in the rat: effects of age and intoxicated practice.

An animal model of human reaction time (RT) was used to investigate the effects of age and intoxicated practice on the development of tolerance to the motor impairing effects of ethanol (EtOH). Young (8-9 month) and old (24-26 month) Fischer 344 rats were trained to release a lever in response to an auditory and visual stimulus in order to avoid mild footshock. The animals were divided into groups to receive either intoxicated (EtOH-before) or unintoxicated (EtOH-after) RT testing. Successful avoidance and response latencies were impaired in young and old rats after the initial exposure to EtOH (EtOH-before group). Tolerance developed to EtOH's effects on successful avoidance and on response latencies whether or not the rats received intoxicated RT practice; however, intoxicated practice facilitated tolerance development to EtOH's effects on successful avoidance but not on response latencies. While the initial sensitivity and the level of tolerance that developed to EtOH's effects were similar in young and old rats, the old rats were generally more sensitive to EtOH and developed tolerance at a slower rate. These results suggest that tolerance develops to the effects of EtOH on RT and that intoxicated practice can have different effects on the parameters of the behavioral response.

Aging

In vitro formation and expansion of cysts derived from human renal cortex epithelial cells.

Acquired renal cysts derive from terminally differentiated tubular epithelium in adults as a consequence of increased epithelial cell proliferation, fluid accumulation and extracellular matrix remodelling. To understand better how human epithelial cysts may be initiated and progressively expand, cells from primary cultures of normal human adult renal cortex were dispersed in polymerized type I collagen. The transparent matrix permitted repeated observation by light microscopy of cyst formation from individual renal cells. The cyst cells reacted strongly with distal nephron histochemical markers (cytokeratin antibodies AE1/AE3, epithelial membrane antigen, and Arachis hypogaea lectin) but inconsistently or not at all to markers of proximal tubules (Tetragonolobus purpureas lectin and Phaseolus vulgaris erthroagglutinin lectin). The number of spherical, fluid-filled epithelial cysts that developed in a standardized microscope field quantified cyst initiation. Cyst progression was determined from the increase in the diameter (surface area) of cysts and represents a hyperplastic event. EGF or TGF alpha, were required in serum-free defined medium to cause cysts to develop from individual epithelial cells dispersed in the matrix; insulin was required as a co-factor. The EC50 for EGF was approximately 0.1 ng/ml, and for insulin 1 microgram/ml. Early cultures of normal cortex formed cysts more efficiently when dispersed in collagen matrix than cells passaged several times before suspension in the gel. Agonists of adenylate cyclase (PGE1, AVP, VIP, PTH, forskolin, cholera toxin), methylisobutylxanthine, and 8-Br-cAMP, though incapable of causing cyst formation alone in defined medium, enhanced cyst initiation and progression in the presence of EGF and insulin. Angiotensin II, TNF alpha, beta-estradiol, and pertussis toxin had no effect in the absence or presence of EGF and insulin. Pertussis toxin inhibited cyst initiation and expansion caused by EGF and forskolin but potentiated cyst initiation and expansion caused by EGF and PGE1. Cyst formation and expansion were inhibited by TGF beta 1 and 2-chloroadenosine. Polarized monolayers of human renal cortical cells grown on permeable membranes were used to independently quantify the effects of agonists on the net secretion of solute and water from the basolateral to the apical surface of the cells. PGE1, forskolin, and 8-Br-cAMP stimulated net fluid secretion that was sustained for several days; EGF enhanced forskolin-stimulated fluid secretion. We conclude that the formation and expansion of in vitro cysts derived from solitary human cortex cells depends on the coordinated interplay between cellular proliferation and fluid secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Fluids

Methylation of CpG sites of two X-linked genes coincides with X-inactivation in the female mouse embryo but not in the germ line.

To further our understanding of initiation and imprinting of X-chromosome inactivation, we have examined methylation of specific CpG sites of X-linked Pgk-1 and G6pd genes throughout female mouse development. Methylation occurs around the time of inactivation and earlier for Pgk-1, which is closer to the X-inactivation centre. In female primordial germ cells, the inactive X chromosome escapes methylation; this may underly the reversibility of inactivation at meiosis. Similarly, the genes are unmethylated on the inactive X chromosome in sperm; hence, the imprint specifying preferential X-inactivation in extra-embryonic tissues must reside elsewhere.

Animals

Effects of growth factors on corneal wound healing.

Healing of ocular surface wounds is a complex process involving migration, mitosis, and differentiation of epithelial and stromal cells. Endogenously produced peptide growth factors such as epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), or transforming growth factor beta (TGF-beta) may play key roles in the natural wound healing process. Lacrimal gland cells were reported to synthesize and secrete EGF into tear fluid where it may enhance healing of corneal epithelial and stromal injuries by an exocrine pathway. EGF stimulated DNA synthesis of epithelial cells and stromal fibroblasts in culture, stimulated synthesis of fibronectin by epithelial cells and was chemotactic for human epithelial and stromal cells. Human corneal epithelial cells also synthesized TGF-alpha which may influence epithelial cells by an autocrine pathway. TGF-beta, which is a potent inducer of lysyl oxidase mRNA levels in cultures of human scleral fibroblasts, may be the factor most responsible for inducing synthesis of corneal extracellular matrix components after an injury. Treatment of epithelial injuries ocular surface wounds with exogenous peptide growth factors also accelerated healing in rabbits and primates. Treatment of severe ocular surface injuries caused by alkali with a combination of EGF, fibronectin, a synthetic collagenase inhibitor, and Aprotinin significantly blocked ulceration and enhanced epithelial regeneration. Clinical trials of topical treatment of EGF for ocular surface wounds suggest that peptide growth factors may be a valuable adjuvant for treatment of ocular surface wounds.

Animals

Cyst fluid from human autosomal dominant polycystic kidneys promotes cyst formation and expansion by renal epithelial cells in vitro.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal enlargement, culminating in renal insufficiency in over one half of affected individuals. The highly variable onset and clinical course of ADPKD may be due to factors extrinsic to the genetically defined renal cysts. In this study, cyst fluid samples from 12 nonazotemic and 18 azotemic ADPKD subjects were examined for in vitro biologic activity that promotes cellular proliferation and the secretion of fluid by renal epithelial monolayers, two pathogenetic mechanisms that have critical roles in the formation and the rate of expansion of renal cysts. Cyst fluid added to culture medium (final concentrations, 1 to 20%) caused Madin-Darby canine kidney cells and human kidney cortex (HKC) cells derived from primary cultures to form cysts in Type I collagen matrix. Cyst fluid stimulated the net transepithelial secretion of fluid by polarized monolayers composed of these same cells. Absolute levels of fluid secretory activity determined by MDCK bioassay were correlated directly with the rate of fluid secretion by HKC cell monolayers and with the extent of cyst formation by MDCK and HKC cells embedded in collagen matrix. The secretory activity of urine was negligible; secretory activity was detectable in the serum of normal and ADPKD subjects, but the levels were much lower than in cyst fluid. cAMP agonists prostaglandins E1 and E2, arginine vasopressin, and 8-Br-cAMP stimulated fluid secretion by MDCK and HKC monolayers, but these substances did not cause HKC cells to form cysts in collagen matrix, whereas cyst fluid did. Among other naturally occurring growth factors and autacoids, only epidermal growth factor and transforming growth factor alpha stimulated cyst formation by HKC cells; however, the capacity of cyst fluid to stimulate fluid secretion was not affected by treatment with antiserum to epidermal growth factor. It was concluded that potent, and possibly unique, substances in the cyst fluids of individuals with ADPKD support and augment biologic processes in renal epithelial cells that may be important in the promotion of progressive cyst expansion.

8-Bromo Cyclic Adenosine Monophosphate

Analgesic use in home hospice cancer patients.

BACKGROUND: Pain control in hospice patients in the home may be compromised by concerns about overuse of analgesics, particularly narcotics. METHODS: A retrospective chart audit of analgesic type and amount was performed on the medical records of 100 cancer patients receiving hospice care in the home. Different types and amounts of analgesics were converted to a common standard, an oral morphine equivalent (OME) relative to 1 mg of oral morphine sulfate. Descriptive statistics were used to characterize patient analgesic use during the entire course of hospice care and the last 5 days of life. Associations between analgesic use and select patient characteristics (age, sex, cancer site, metastases, and pain intensity at admission) were explored. RESULTS: Ninety-one percent of the sample had used analgesics at some time during hospice care. The proportion of patients using analgesics increased as death approached. The mean and median daily analgesic use over the entire period were 114 and 82 OMEs and during the last 5 days 140 and 84 OMEs, respectively. The range of mean daily analgesic use was between 10 and 735 OMEs. CONCLUSIONS: Individual variability in analgesic use was demonstrated. Not all patients required analgesics, and among those who did there was remarkable variation in the amount used. Large and even enormous doses of analgesics may sometimes be required to control cancer pain.

Aged

The meaning of quality of life for bone marrow transplant survivors. Part 2. Improving quality of life for bone marrow transplant survivors.

Surviving bone marrow transplant (BMT) represents a major victory against malignant disease but also creates challenges of survivorship for patients and the professionals who care for them. Part 2 of this report presents the findings of a qualitative study (N = 119) related to improving quality of life (QOL) for BMT survivors. Results are shared based on BMT survivors' perceptions of (a) what makes QOL better, (b) what makes QOL worse, and (c) what doctors or nurses could do to enhance QOL. The findings of the study have been useful in constructing a quantitative instrument to measure QOL in BMT and in understanding the conceptual basis of QOL for the BMT population. Nursing interventions can improve the QOL for the BMT patient across all phases of the transplant process and long-term issues related to survival.

Bone Marrow Transplantation

The meaning of quality of life for bone marrow transplant survivors. Part 1. The impact of bone marrow transplant on quality of life.

Quality of life (QOL) is an important concept in cancer nursing and has particular significance for bone marrow transplant (BMT). BMT survivors are faced with the demands of acute transplant symptoms as well as chronic illness demands posttransplant. The purpose of this study was to explore the concept of QOL for BMT survivors and to gain understanding of nursing interventions that may improve QOL in this population. The conceptual framework for this study was derived from the model of QOL developed by Ferrell, Grant, and Padilla (1989) that depicts the QOL domains of physical well-being, psychological well-being, social concerns, and spiritual well-being. This qualitative study consisted of a one-time interview of 119 BMT survivors using six open-ended questions. The items were based on previous research of the authors and content validity was established by a panel of BMT experts. Content analysis was performed on verbatim written responses to six questions regarding BMT and QOL. Part one of this two-part report provides analysis based on the questions regarding the meaning of QOL to BMT survivors and the impact of BMT on QOL.

Adult

Iliad training enhances medical students' diagnostic skills.

Iliad is a computerized, expert system for internal medical diagnosis. The system is designed to teach diagnostic skills by means of simulated patient case presentations. We report the results of a controlled trial in which junior students were randomly assigned to received Iliad training on one of two different simulated case mixes. Each group was subsequently tested in both their "trained" and "untrained" case domain. The testing consisted of computerized, simulated patient cases for which no training feedback was provided. Outcome variables were designed to measure the students' performance on these test cases. The results indicate that students made fewer diagnostic errors and more conclusively confirmed their diagnostic hypotheses when they were tested in their trained domain. We conclude that expert systems such as Iliad can effectively teach diagnostic skills by supplementing trainees' actual case experience with computerized simulations.

Clinical Clerkship

The experience of pain and perceptions of quality of life: validation of a conceptual model.

Pain is a common symptom of terminally ill cancer patients and a major challenge for hospice care. This paper presents a conceptual model of the relationship between pain and quality of life that was derived from the authors' previous research. The model should prove useful to hospice clinicians and researchers in evaluating the impact of palliative care on the quality of life.

Evaluation Studies as Topic

A six country survey of the content and structure of heroin treatment programmes using methadone.

The use of methadone in the treatment of drug dependence has provoked a good deal of controversy. However, it is clear that there is considerable variation between methadone treatment programmes and relatively little detail is available about the organization and operation of these programmes. This World Health Organization survey examines the content and structure of methadone treatment programmes, and particularly methadone maintenance programmes, in six countries. The six countries were Australia, Canada, France, the Netherlands, Thailand and the UK. The report presents information about the extent of national problems and about such issues as type of dispensing practices, dose- and time-limits for prescribing methadone, programme entry criteria, staffing, integration with other services, and urine testing. Developments and trends during the decade 1980-1990 are discussed and implications for further research and programme development are presented.

Cross-Cultural Comparison

Brief exercise induces an immediate and a delayed leucocytosis.

Haematological profiles were measured: (1) before and for 5 h 30 min after 30 min sports (squash, swimming, jogging); and (2) before, during and for 2 h 30 min after 30 min cycle ergometry at workloads which required rates of oxygen consumption that were between 48% and 84% of maximal. In both instances exercise induced an immediate leucocytosis (owing to rises in both neutrophils and lymphocytes) which subsided rapidly at the finish of exercise and was followed by a delayed neutrophilia of greater magnitude which peaked at approximately 3 h after the start of exercise. Changes in plasma catecholamines and cortisol recorded during and after exercise (cycle ergometry only) support the hypothesis that the immediate leucocytosis during brief exercise is attributable to elevated catecholamine levels, whereas the delayed neutrophilia is due to raised cortisol levels.

Adult

Family factors influencing cancer pain management.

The purpose of this study was to describe family factors which influence cancer pain. Previous research has focused on the patients' and professional caregivers' perspective of pain. Cancer pain is an intense burden on the entire family as well as on the patient. Findings of the study demonstrate family perceptions of pain, caregiver burden associated with pain, caregiver moods and differences in caregiver experiences of pain between three sites of care including a hospice, a community hospital and a cancer centre. Understanding the perspective of the family caregivers and their role in pain management can assist health care providers in management of the patient's pain.

Adult

Clinical decision making and pain.

Pain management is intimately linked to decision making. Nurses play a key role in making decisions regarding pain and its management. This paper presents data from a preliminary study (N = 53) extending the investigators' pain research into the areas of clinical decision making and ethical dilemmas related to pain management. Nurses completed surveys focused on actual experiences of caring for patients in pain. The results identify common clinical decisions related to pain, barriers to providing optimum pain relief, and ethical/professional conflicts in pain management. Decisions related to the amount of pain intensity, when to give medications, and choice of analgesics. Nurses identified verbal and nonverbal cues central to their decisions regarding pain assessment. Barriers to effective pain management included physician knowledge and cooperation, patient/family knowledge and cooperation, as well as nursing knowledge and time. Respondents identified ethical dilemmas about overmedication or undermedication, conflicts with physicians or patients, and concern over opioid side effects. A tentative model of decision making related to pain is presented.

Adult