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Biomedical subjects

C Cameron

Publications and source records attributed to C Cameron.

At least 37 records · Page 2Linked to original sources

Relationships among sleep dimensions and factors that impair sleep after cardiac surgery.

Factors associated with the attempted length, disturbance, effectiveness, and nap supplementation of sleep were analyzed in 97 patients recovering from cardiac surgery a few days before hospital discharge. Patients rated sleep for the prior night and factors that impaired their sleep after transfer from the critical care unit. The group averaged little sleep, with moderate disturbance and effectiveness and low nap supplementation. The disturbance, effectiveness, and attempted length of sleep were associated with an inability to perform their usual routine before sleep, inability to get comfortable, pain, noises, procedural care, and an unfamiliar bed. Patients encounter difficulties with sleep, even near discharge from the hospital. Interventions should be tested to mitigate specific factors that affect selected dimensions of sleep.

Adult↗

Patient compliance: recognition of factors involved and suggestions for promoting compliance with therapeutic regimens.

Patient compliance is paramount in the effectiveness of therapeutic regimens. Without compliance therapeutic goals cannot be achieved, resulting in poorer patient outcomes. The social and psychological factors thought to influence compliance are identified as (a) knowledge and understanding including communication, (b) quality of the interaction including the patient-provider relationship and patient satisfaction, (c) social isolation and social support including the effect of the family, (d) health beliefs and attitudes-health belief model variables, and (e) factors associated with the illness and the treatment including the duration and the complexity of the regimen. Noncompliance is a significant problem and a major challenge for the health care team. Practical advice is offered for nurses and other health care professionals to increase patient compliance with therapeutic regimens. These include factors involved in the patient-provider relationship, communication skills and information-giving, and the mobilization of existing social support networks. Further research is needed to provide more conclusive results into the factors involved in patient compliance and to test the effectiveness of compliance-enhancing strategies.

Attitude to Health↗

Patient advocacy: a role for nurses?

There is much controversy surrounding the issue of nurses in the role of patient advocate. Cancer patients are vulnerable due to their diagnoses, the anxiety that it generates, the nature of the disease and subsequent treatment and may diminished autonomy as a result. It is questionable whether the nurse is able to promote the best interest of the patient in this situation. Models of advocacy and the nurse-patient relationship are discussed. The main arguments for taking on the role of patient advocate include: reference to long periods of time spent with patient and the chance to build a relationship; on duty to care and the duty to do no harm. Criticisms of the appropriateness of advocacy role for nurses include: inability for the patient to choose his or her nurse; promotion of self interests; charges of paternalism; challenges from other health care professionals and multiple and/or conflicting obligations. It is concluded that perhaps the most ethical way of caring is by empowering patients and promoting self-advocacy. This concept needs to be further explored.

Ethics, Nursing↗

Haemolytic-uraemic syndrome in Western Australia, 1980 to 1994.

A retrospective, population-based study of patients hospitalised with the haemolytic-uraemic syndrome in Western Australia from 1980 to 1994 was undertaken to describe the epidemiology of the disease in this state. We identified 41 patients. Episodes were commonest in children under five years of age (63.4 per cent) and were more frequent in females (58.5 per cent) than in males; only one Aboriginal patient was detected. More than 90 per cent of episodes had a gastrointestinal prodrome lasting from one to 22 days; in 47.6 per cent of these episodes patients had bloody diarrhoea. The average hospital stay was 26 days, and 63.4 per cent of patients required dialysis (mean 10 days). More than 20 per cent of patients developed chronic renal failure, 9.7 per cent died, two patients developed hypertension and one child became epileptic; three of the 10 patients over 16 years of age (30 per cent) died. The haemolytic-uraemic syndrome is potentially fatal, affects mostly young children, and is usually preceded by a gastrointestinal illness. Episodes can occur in common-source outbreaks but, with the exceptions of related cases in families, that appears not to have been so in Western Australia since 1980. There is a need for increased awareness of the haemolytic-uraemic syndrome to enhance prospects for earlier detection and better clinical outcomes. Improved public health surveillance is also needed to reduce the risks of the syndrome in the community.

Adolescent↗

Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia.

Cell line NKL was established from the the peripheral blood of a patient with CD3-CD16+CD56+ large granular lymphocyte (LGL) leukemia. The neoplastic LGL of this patient mediated natural killing and antibody-dependent cellular cytotoxicity (ADCC) and exhibited proliferative responses similar to normal CD16+CD56dim natural killer (NK) cells. The Morphology of NKL cells resembles that of normal activated NK cells. The karyotype of NKL is 47, XY, add (1) (q42), +6 del (6) (q15 q23), del (17) (p11). NKL cells express CD2, CD6, CD11a, CD26, CD27, CD29, CD38, CD43, CD58, CD81, CD94, CD95, class II MHC, and the C1.7.1 antigen, but do not express detectable levels of CD3, CD4, CD5, CD8, CD14, CD19, CD20, CD28, alpha/beta or gamma/delta T cell receptors on the cell surface. The density of the CD16, CD56, and CD57 antigens declined markedly on NKL cells during prolonged im vitro culture. Nevertheless, NKL cells can mediate ADCC as well as natural killing. NKL cells are strictly dependent on interleukin-2 (IL-2) for sustained growth and die if deprived of IL-2 for more than 7 days. NKL cells proliferate in response to concentrations of IL-2 as low as 1 pM, but an optimal proliferative response requires approximately 100 pM IL-2. NKL cells growing in the presence of IL-2 express abundant IL-2R alpha with little or no detectable IL-2 beta or gamma chain on the cell surface; NKL cells deprived of IL-2 express high levels of both IL-2R alpha and beta. IL-4, IL-7, and IL-12, unlike IL-2, do not maintain the viability of NKL cells. Furthermore, IL-1, IL-4, IL-6, IL-7, IL-12, tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha) and IFN-gamma do not support the growth of NKL cells. The NKL cell line may prove useful for studies of human NK cell biology.

Antigens, CD↗

Patients' perceptions of environmental factors that disturb sleep after cardiac surgery.

BACKGROUND: Effective management of sleep disturbances after cardiac surgery requires insight into patients perceptions of which factors disturb sleep in the intensive care unit and after transfer from the intensive care unit. OBJECTIVE: To describe patients perceptions of environmental factors that disturbed sleep after cardiac surgery. SAMPLE: A convenience sample of 102 patients was surveyed in a 300-bed, acute-care teaching hospital. METHOD: Patients were interviewed several days before discharge from the hospital and rated the extent to which specific factors disturbed their sleep while in the intensive care unit and after transfer. RESULTS: The group mean for the extent of disturbance scores, averaged across all 35 environmental factors studied, was low during and after stay in the intensive care unit. However, selected items such as pain, and inability to get comfortable and perform a familiar nighttime routine, were moderately disturbing to many patients across phases of recovery. Patients varied widely in the number of factors, ranging from 0 to 33 factors, that disturbed sleep at least to some extent. Patients added factors that were not included in the original monitoring instrument. CONCLUSIONS: Patients attribute disturbed sleep to specific factors after cardiac surgery. The number of factors that disturb sleep varies among patients. Nurses can modify many of the factors that disturb sleep to promote an environment that will facilitate improved sleep, thereby enhancing the acute phase of recovery from cardiac surgery.

Aged↗

School-age children's perceptions of mental illness.

The purpose of this study was to describe how school-age children perceive mental illness. The specific aims of this study were to describe the impact of age and sex on children's ability to identify and classify deviant behavior, and to identify how school-age children perceive mental illness by looking at how they define the concept, characterize the mentally ill, and understand causality and treatment. The random sample consisted of 90 school-age children. Thirty children were in grade 1, 30 in grade 4, and 30 in grade 7. A multimethods approach combining qualitative and quantitative techniques was used to analyze data. Major study findings indicated that age was not a significant factor in children's ability to classify deviant behavior; however, there was a sex main effect: Boys were able to better identify deviant behaviors than girls. A developmental trend was noted in children's ability to be aware of what mental illness is, to acknowledge characteristics of people who are mentally ill, to differentiate between mental illness and mental retardation, to identify various etiologies of mental illness, and to choose appropriate treatment modalities.

Adolescent↗

Functional consequences of APO-1/Fas (CD95) antigen expression by normal and neoplastic hematopoietic cells.

Murine monoclonal antibody (mAb) 7C11 binds to the same cell surface epitope as anti-APO-1 and anti-Fas and reacts specifically with cells transfected with a cDNA encoding the human Fas antigen. Furthermore, incubation with 7C11 causes death of hematopoietic cell lines that express APO-1/Fas but not APO-1/Fas-negative cell lines. 7C11 therefore recognizes the human APO-1/Fas (CD95) antigen, a 40 to 50 kDa cell surface glycoprotein that can trigger apoptosis or programmed cell death. Expression of APO-1/Fas antigen by normal and neoplastic hematopoietic cells was determined by flow cytometry using 7C11. APO-1/Fas is expressed by approximately 30 to 40% of resting peripheral blood T cells, B cells, and monocytes and by approximately 5% of resting NK cells and thymocytes. It was not detected on granulocytes, erythrocytes, or platelets. Approximately 80 to 90% of activated T cells, B cells, and thymocytes express APO-1/Fas, as do the majority of activated NK cells. Perturbation of APO-1/Fas by 7C11 does not affect the viability of resting lymphocytes or monocytes. In contrast, activated T cells and NK cells undergo apoptosis within 3 hours of exposure to 7C11. Other mAb that stimulate T cells or NK cells do not cause rapid induction of programmed cell death. APO-1/Fas antigen is expressed by many cell lines of lymphoid and myeloid lineage. However, this antigen was detected on neoplastic cells from only one of 69 patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, or multiple myeloma. Only 3 out of 25 tumor samples from patients with non-Hodgkin's lymphoma were found to express APO-1/Fas. All three of these lymphomas harbored the bcl-2-Ig fusion gene associated with the chromosomal translocation t (14;18). Conversely, only 27% of lymphomas that possessed the bcl-2-Ig gene were found to express the APO-1/Fas antigen. Like normal activated lymphocytes, leukemia and lymphoma cells that expressed APO-1/Fas antigen were found to undergo apoptosis in vitro after incubation with 7C11. The APO-1/Fas antigen appears to regulate the growth of normal hematopoietic cells, and the marked upregulation of this antigen on activated normal lymphocytes contrasts sharply with the absence of APO-1/Fas on neoplastic cells of hematopoietic lineage. Defects in the apoptotic signal delivered through this antigen might contribute to the pathogenesis of hematopoietic neoplasms. Thus, the gene encoding APO-1/Fas can be considered a novel type of tumor suppressor gene, just as bcl-2 can be considered a cellular proto-oncogene.

Animals↗

Combination chemotherapy with gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: preliminary results of an ongoing phase I/II study.

Collaborative phase I and II studies of the combination of gemcitabine and cisplatin in patients with advanced non-small cell lung cancer are ongoing at five centres in the UK and France. In the initial completed phase I study, 16 patients (15 evaluable) have been entered using a fixed dose of gemcitabine 1000 mg/m2 given as a 30 min intravenous infusion weekly for 3 weeks. On the third week the gemcitabine was immediately followed by cisplatin with pre- and post-hydration. This regimen required only 1 night of hospitalization every 4 weeks. The study design was for sequential groups of patients to receive 3 dose levels of cisplatin (60 mg/m2, 75 mg/m2 and 100 mg/m2) but these doses would be modified and the number of patients at any dose level could be increased if significant toxicity was observed. Three patients were to be entered at the first two dose levels and 10 patients were to confirm the maximum tolerated dose (if reached) or expand the database on toxicity at the final predetermined dose level. The major haematological toxicities were neutropenia (grade 4 in 3 patients) and thrombocytopenia (grade 3 or 4 in 5 patients) but both were of short duration and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients but was no worse than would be expected from cisplatin alone. Alopecia was not a problem (no hair loss in 10 patients and grade 1 or 2 in 6 patients) and no significant renal or neurotoxicity was seen. A phase II study using cisplatin 100 mg/m2 in combination with gemcitabine 1000 mg/m2 has been opened and to date 19 patients are evaluable for response. Eight (42%) have achieved partial remissions. The study is ongoing and will recruit 50 evaluable patients.

Antimetabolites, Antineoplastic↗

Prediction of graft-versus-host disease by phenotypic analysis of early immune reconstitution after CD6-depleted allogeneic bone marrow transplantation.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT). Because GVHD is frequently refractory to treatment, the early identification of high-risk patients could have significant clinical value. To identify such patients, we examined early immunologic recovery in 136 patients with hematologic malignancies who received anti-T12 (CD6)-purged allogeneic bone marrow over a 9-year period. The majority of patients received marrow from HLA-matched sibling donors after ablation with cyclophosphamide and total body irradiation. No patients received any immune suppressive medications for GVHD prophylaxis. The fraction and absolute numbers of peripheral blood lymphocytes (PBL) expressing the CD3, CD4, CD8, and CD56 surface antigens were determined weekly by immunofluorescence analysis in patients beginning 8 to 14 days (week 2) after marrow infusion. Results in patients who did or did not subsequently develop GVHD post-BMT were compared. Within 2 weeks of marrow infusion, patients who developed grades 2-4 GVHD had significantly higher percentages and absolute numbers of CD8+ T cells and a lower fraction of CD56+ natural killer (NK) cells than individuals who remained free of GVHD. Thirty-five percent of patients whose PBL were greater than 25% CD8+ in the second posttransplant week developed GVHD, compared with only 3% of patients who had < or = 25% CD8+ cells (odds ratio 37.8; 95% confidence interval [CI] 4.1 to 397). A subgroup of patients at very high risk for GVHD could be identified based on the combined frequency of CD8+ T cells and NK cells in blood. Seventy-five percent of patients with greater than 25% CD8+ cells and < or = 45% CD56+ cells during week 2 post-BMT developed GVHD, compared with only 11% of the remaining patients (odds ratio 24.9; 95% CI, 5.3 to 117.0). None of the 23 patients with both less than 25% CD8+ cells and greater than 45% CD56+ cells in the second posttransplant week developed grades 2-4 GVHD. Our findings indicate that CD8+ T cells play an important role in the pathogenesis of GVHD in humans. Analysis of immune reconstitution early after BMT is useful in predicting the onset of GVHD and can help direct the implementation of treatment strategies before the appearance of clinical manifestations. Such interventions may decrease the morbidity and mortality associated with allogeneic BMT and ultimately improve overall survival.

Adult↗

Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2.

The immunologic consequences of prolonged infusions of rIL-2 in doses that produce physiologic serum concentrations of this cytokine were investigated. rIL-2 in doses of 0.5-6.0 x 10(6) U/m2 per d (3.3-40 micrograms/m2 per d) was administered by continuous intravenous infusion for 90 consecutive days to patients with advanced cancer. IL-2 concentrations (25 +/- 25 and 77 +/- 64 pM, respectively) that selectively saturate high-affinity IL-2 receptors (IL-2R) were achieved in the serum of patients receiving rIL-2 infusions of 10 micrograms/m2 per d and 30 micrograms/m2 per d. A gradual, progressive expansion of natural killer (NK) cells was seen in the peripheral blood of these patients with no evidence of a plateau effect during the 3 mo of therapy. A preferential expansion of CD56bright NK cells was consistently evident. NK cytotoxicity against tumor targets was only slightly enhanced at these dose levels. However, brief incubation of these expanded NK cells with IL-2 in vitro induced potent lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Infusions of rIL-2 at 40 micrograms/m2 per d produced serum IL-2 levels (345 +/- 381 pM) sufficient to engage intermediate affinity IL-2R p75, which is constitutively expressed by human NK cells. This did not result in greater NK cell expansion compared to the lower dose levels, but did produce in vivo activation of NK cytotoxicity, as evidenced by lysis of NK-resistant targets. There was no consistent change in the numbers of CD56- CD3+ T cells, CD56+ CD3+ MHC-unrestricted T cells, or B cells during infusions of rIL-2 at any of the dosages used. This study demonstrates that prolonged infusions of rIL-2 in doses that saturate only high affinity IL-2R can selectively expand human NK cells for an extended period of time with only minimal toxicity. Further activation of NK cytolytic activity can also be achieved in vivo, but it requires concentrations of IL-2 that bind intermediate affinity IL-2R p75. Clinical trials are underway attempting to exploit the differing effects of various concentrations of IL-2 on human NK cells in vivo.

Antibody-Dependent Cell Cytotoxicity↗

Characterization of the original Christmas disease mutation (cysteine 206----serine): from clinical recognition to molecular pathogenesis.

Christmas disease was first reported as a distinct clinical entity in two manuscripts published in 1952. The eponym associated with this disorder, is the surname of the first patient examined in detail and reported by Biggs and colleagues in a paper describing the clinical and laboratory features of seven affected individuals. This patient has severe factor IX coagulant deficiency (less than 0.01 units/ml) and no detectable circulating factor IX antigen (less than 0.01 units/ml). Coding sequence and splice junctions of the factor IX gene from this patient have been amplified in vitro through the polymerase chain reaction (PCR). One nucleotide substitution was identified at nucleotide 30,070 where a guanine was replaced by a cytosine. This mutation alters the amino acid encoded at position 206 in the factor IX protein from cysteine to serine. The non conservative nature of this substitution, the absence of this change in more than 200 previously sequenced factor IX genes and the fact that the remainder of the coding region of this gene was normal, all provide strong circumstantial evidence in favour of this change being the causative mutation in this patient. The molecular characterization of this novel mutation in the index case of Christmas disease, contributes to the rapidly expanding body of knowledge pertaining to Christmas disease pathogenesis.

Amino Acid Sequence↗

Clinical and immunologic effects of prolonged infusion of low-dose recombinant interleukin-2 after autologous and T-cell-depleted allogeneic bone marrow transplantation.

Bone marrow transplantation (BMT) can produce prolonged clinical remission in some patients with hematologic malignancies. Unfortunately, disease relapse may occur despite BMT. Studies in animal models and clinical experience have provided evidence that immunologic factors play an important role in preventing relapse post-BMT. To stimulate immunologic activity in patients post-BMT, we administered prolonged uninterrupted continuous infusions of low-dose recombinant interleukin-2 (rIL-2). Thirteen marrow recipients (seven autologous BMT, six CD6 T-depleted allogeneic BMT) received rIL-2 at a dose of 2 x 10(5) U/m2/d for a scheduled period of 90 days. rIL-2 was administered through a Hickman catheter with a portable pump beginning a median of 85 days after BMT. Toxicity was minimal and all treatment could be undertaken in the outpatient setting. No patient developed any signs of graft-versus-host disease, hypotension, or pulmonary capillary leak syndrome. Treatment did not affect the absolute neutrophil count or hemoglobin level, but eosinophils increased substantially in most patients. Platelet counts decreased by 20% in 10 of 13 individuals within 2 weeks, but stabilized thereafter. Despite the low dose of rIL-2 administered, significant immunologic changes were noted. Specifically, all 13 patients experienced a marked increase (fivefold to 40-fold) in natural killer (NK) cell number. Phenotypic characterization showed that the majority of NK cells were CD56bright+ CD16+ CD3-. In contrast, a minor increase in T-cell number was noted in only 4 of 13 patients. Low-dose rIL-2 treatment resulted in augmentation of in vitro cytotoxicity against K562 and COLO tumor targets. This cytotoxic activity could be dramatically enhanced by incubation with additional rIL-2 in vitro. The immunologic effects of rIL-2 treatment were similar in both autologous and allogeneic marrow recipients. Our data suggest that prolonged infusion of rIL-2 at low doses is safe and can selectively increase NK cell number and activity after BMT. Further studies to assess the impact these changes may have on disease relapse post-BMT will be undertaken.

Adult↗

Differential termination of primer extension: a novel, quantifiable method for detection of point mutations.

We have developed a novel technique that is useful for the rapid detection of previously characterized point mutations in the human genome. The method relies on the differential termination of primer extension being performed simultaneously on normal and mutant template molecules in the presence of a selectively limited complement of deoxynucleotide triphosphates. We have used this technique to determine the carrier status of two potential carriers of a hemophilia B mutation at codon 145 in the factor IX gene. In addition, the technique has been used to quantify the levels of mutant sequence in several tissues of a hemophilia B patient who is a somatic mosaic for a point mutation at codon 350.

Base Sequence↗

Absence of allelic loss on chromosome 5q by RFLP analysis in preleukemia.

Thirty-eight patients with various forms of myelodysplastic syndrome (MDS) were studied for the loss of restriction fragment length polymorphism (RFLP) heterozygosity on chromosome 5q as inferential support for the presence of a growth regulatory locus in this area of the genome. Conventional chromosomal analysis was performed in addition to RFLP studies of constitutive and granulocyte DNA using five polymorphisms from chromosome 5. Allelic loss in granulocyte DNA was identified in only one patient in whom monosomy 5 had already been defined cytogenetically. These results suggest that DNA sequence loss from chromosome 5q other than that observed cytogenetically is a rare event in MDS. Thus the potential involvement of a growth regulatory gene(s), from this area of the genome, in the leukemogenic process most likely involves a more subtle genetic change.

Alleles↗

Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states.

Adult↗

The ethnographic approach: characteristics and uses in gerontological nursing.

Ethnography presents the researcher with a methodology for studying meaning carefully; a process for going beyond what is seen or heard to infer what people know by careful listening and observation of behavior, environment, and context. Ethnography describes and explains both regularities and variations in human behavior; the method accommodates the careful description of irregularities in a complex society that may not be or cannot be explained in traditional theory. Ethnography can strengthen traditional methods of theory development generally and gerontological nursing specifically. The descriptive value of ethnography as a qualitative research method to generate concepts, theories, and hypotheses in substantive knowledge areas within gerontological nursing is recognized.

Aged↗