NCCN sarcoma practice guidelines. National Comprehensive Cancer Network.
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Humans↗
Biomedical subjects
L Baker
Publications and source records attributed to L Baker.
End-of-life confusion in patients with cancer.
PURPOSE/OBJECTIVES: To review the literature on confusion at the end of life, provide accurate definitional and defining characteristics of confusion, and outline nursing strategies for its resolution. DATA SOURCES: Published articles, computerized databases, book chapters, reference lists from chapters and journal articles. DATA SYNTHESIS: As a major component of symptom distress in terminal care, confusion has not been defined clearly and therefore has not benefited from rigorous assessment and study as have other end-of-life symptoms. CONCLUSIONS: Increased knowledge about confusion that occurs in patients with widely metastatic cancer will assist in accurate symptom identification, early recognition, and timely management to reduce cognitive symptom distress at the end of life. Improved symptom resolution also can benefit family coping during terminal care. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can devise management protocols for confused patients that include screening criteria, pharmacologic interventions, environmental support, and prophylactic safety measures.
Confusion↗
Characterization of the Ras binding domain of the RalGDS-related protein, RLF.
The Ras binding domain (RBD) of Rlf, a member of the RalGDS family of proteins, was characterized. Using an ELISA-based technique, the relative binding affinity of Rlf for a variety of mutant Ras proteins was determined. Rlf had significantly different binding characteristics than the Raf-1 RBD. The minimal effective Ras binding domain was defined as residues 657-778 using N- and C-terminal deletions of Rlf. Using the PHD algorithm, the secondary structure of this domain was predicted to be similar to the ubiquitin superfold previously identified in the Raf-1 RBD. When the predicted secondary structure of the Rlf-RBD was aligned with the known secondary structure of the Raf-RBD, amino acids in Raf-1 essential for Ras binding were found to also be conserved in Rlf. Consistent with this observation, alanine substitution of one of these residues (K687) in Rlf significantly reduced affinity for Ras-GTP.
Amino Acid Sequence↗
Mycophenolate mofetil for obliterative bronchiolitis syndrome after lung transplantation.
BACKGROUND: The development of obliterative bronchiolitis after lung transplantation portends a poor long-term outcome because of progressive decline in allograft function. There are currently no effective means of treating this condition. METHODS: Thirteen patients in whom obliterative bronchiolitis syndrome developed after lung transplantation were treated with mycophenolate mofetil, an antimetabolite immunosuppressant, at a dose of 1.5 g orally twice daily. Patients were followed up clinically and with pulmonary function testing. RESULTS: Duration of mycophenolate mofetil therapy ranged from 1 week to 24 months (mean duration, 11.4 months). Pulmonary function test results stabilized in the majority of patients with no significant further decline in forced expiratory volume in 1 second. Two patients died of progressive obliterative bronchiolitis, 1 patient is alive with progressive disease, and 1 patient died of an acute infection. The drug was discontinued in 2 additional patients. In no patient did severe leukopenia or cytomegalovirus infection develop; 1 patient had a fungal infection, and 7 patients experienced gastrointestinal side effects. CONCLUSIONS: In the setting of obliterative bronchiolitis syndrome, mycophenolate mofetil is generally well tolerated and is associated with stabilization of pulmonary function test results. These findings suggest that the otherwise progressive process of obliterative bronchiolitis can be slowed.
Adult↗
Insulin-like growth factor binding protein-1 levels in the diagnosis of hypoglycemia caused by hyperinsulinism.
The diagnosis of hypoglycemia caused by hyperinsulinism may be difficult because insulin levels are not uniformly elevated at the time of hypoglycemia. Insulin-like growth factor binding protein-1 (IGFBP-1) is a 28 kd protein whose secretion is acutely inhibited by insulin. We hypothesized that serum levels of IGFBP-1 would be a useful marker of hyperinsulinism. We measured IGFBP-1 levels during the course of standardized fasting studies in hospitalized children; 36 patients became hypoglycemic during the fasting studies, and samples obtained at the point of hypoglycemia were analyzed. On the basis of the currently used diagnostic criteria, 13 children had hyperinsulinism, 16 had ketotic hypoglycemia or no disorder, 3 had hypopituitarism or isolated growth hormone deficiency, 2 had glycogen storage disease type 1 and 2 had fatty acid oxidation disorders. In control subjects (children with ketotic hypoglycemia or no disorder), IGFBP-1 levels rose during fasting to a mean of 343.8 +/- 71.3 ng/ml in the sample drawn at the time of hypoglycemia. Mean IGFBP-1 levels at hypoglycemia for the entire group with hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from levels seen in control subjects (p < 0.0001). In children with moderately controlled hyperinsulinism (fasting tolerance > 4 hours), mean IGFBP-1 levels at the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IGFBP-1 levels in the children with poorly controlled hyperinsulinism (fasting tolerance < 4 hours) failed to rise during fasting, with a mean of 30.1 +/- 10.4 ng/ml in the final sample. IGFBP-1 levels were inversely correlated with serum insulin and C-peptide levels (r = -0.71 and -0.72, respectively; p < 0.0001). Patients with other endocrinologic or metabolic diseases that result in fasting hypoglycemia demonstrated a rise in IGFBP-1 levels similar to that seen in ketotic hypoglycemia. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an additional marker of insulin action that might help to differentiate hyperinsulinism from other hypoglycemic disorders.
Adolescent↗
Depression, delusions, and hallucinations in Alzheimer's disease: no relationship to apolipoprotein E genotype.
The apolipoprotein E (APOE) locus on chromosome 19 has been shown to modify risk, and age at onset, of Alzheimer's disease (AD). The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus. Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28% had major depression, 17% had minor depression, 30% had delusions, and 14% had hallucinations; 69% were carriers of at least one APOE E4 allele (14% homozygous E4/E4, 49% heterozygous E3/E4, 6% heterozygous E2/E4, 29% homozygous E3/E3, 2% heterozygous E2/E3). Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes. Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology.
Aged↗
Major and minor depression in Alzheimer's disease: prevalence and impact.
One hundred nine outpatients with Alzheimer's disease (AD) were neuropsychiatrically evaluated and rated on standardized measures of depression, activities of daily living (ADL), nonmood behavioral disturbance, and burdensome events such as serious wandering, falls, and accidents. Distribution of depression scores revealed three patient groups: very few depressive symptoms (51%), minor depression (27%), and major depression (22%). Major depression was associated with substantially greater impairment in ADL, worse nonmood behavioral disturbance (such as aggression), and more frequent serious wandering, even after adjusting for severity of dementia or comorbid health problems. Minor depression was also associated with nonmood behavioral disturbance and wandering. The authors conclude that both major and minor depression are common in AD and produce considerable mood and nonmood morbidity affecting both patients and caregivers. Efforts are warranted to identify and treat depression in AD.
Aged↗
Dual hormonal replacement therapy with insulin and recombinant human insulin-like growth factor (IGF)-I in insulin-dependent diabetes mellitus: effects on the growth hormone/IGF/IGF-binding protein system.
Patients with insulin-dependent diabetes mellitus (IDDM) exhibit abnormalities in the GH/insulin-like growth factor (IGF) axis, including GH hypersecretion, low serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels, and elevated IGFBP-1 levels. We recently demonstrated that in IDDM, dual hormonal replacement therapy with insulin plus recombinant human IGF-I (rhIGF-I) improves glycemic control better than insulin alone. To determine whether the addition of rhIGF-I therapy to insulin therapy also corrects GH/IGF/ IGFBP abnormalities, we examined the effects of chronic combined rhIGF-I/insulin therapy on key components of the somatotropin axis. Forty-three pediatric IDDM patients were randomly assigned to groups receiving daily, fasting subcutaneous injections of placebo or rhIGF-I (80 micrograms.kg.day) for 28 days, while continuing to receive splitmix insulin therapy and intensive outpatient management. rhIGF-I therapy corrected IGF-I deficiency, suppressed IGFBP-1 levels (P < 0.01), and induced a trend toward lower circulating GH levels throughout the study. rhIGF-I therapy also induced an approximate 50% decrease in IGF-II levels (P < 0.001) and an approximate 70% increase in IGFBP-2 levels (P < 0.05). Serum IGFBP-3 levels, normal before treatment, remained normal during rhIGF-I administration. All effects were apparent during the first week of rhIGF-I therapy and persisted throughout treatment. Because improvements in the GH/ IGF axis abnormalities and in glycemic control were greater in subjects receiving combined rhIGF-I and insulin, these data strongly support the concept that dual hormonal replacement in IDDM may offer distinct therapeutic advantages over insulin monotherapy.
Adolescent↗
Dual hormonal replacement with insulin and recombinant human insulin-like growth factor I in IDDM. Effects on glycemic control, IGF-I levels, and safety profile.
OBJECTIVE: To examine if dual replacement with insulin and rhIGF-I, recombinant human insulin-like growth factor I (rhIGF-I) may be safe and result in improved metabolic control and reduced insulin usage. RESEARCH DESIGN AND METHODS: Forty-three patients with IDDM were randomized to receive a daily injection of rhIGF-I (80 mcg/kg s.c.) or placebo while on conventional insulin therapy for 4 weeks. Insulin was adjusted in the attempt to achieve predetermined goal glycemic values. Free and total IGF-I, four daily blood glucoses, and HbA1c were measured. RESULTS: Before randomization, placebo and rhIGF-I groups exhibited low plasma levels of free and total IGF-I, which increased toward normal levels during the treatment period only in the rhIGF group. The regression curve obtained from the average of daily blood glucose measurements indicated that the glycemic profile, overlapping in the lead-in period, exhibited a downward trend in the rhIGF-I group during the treatment period. Mean blood glucose level during the last 10 days of treatment was lower in the rhIGF-I groups (174 +/- 37 vs. 194 +/- 32 mg/dl). HbA1c level was reduced by more than one-half percent more in the rhIGF-I group (-1.85%) than in the control group (-1.3%). The dose of regular insulin was significantly lower in the rhIGF-I group (0.2 +/- 0.1 vs. 0.28 +/- 0.1 U. kg-1. 10 days-1 in the placebo group; P < 0.05). CONCLUSIONS: rhIGF-I in combination with conventional insulin treatment ameliorated the low plasma total and free IGF-I levels and was well tolerated in IDDM. There was a trend toward improved glycemic control, while the regular insulin dose was significantly decreased.
Adolescent↗
Effect of ethnicity on adherence to diabetic regimen.
OBJECTIVE: Evaluating the effectiveness of treatment of diabetic patients in our institution led us to seek the relationship between adherence to diabetic regimens and several demographic variables. Of primary importance was ethnicity, which the practitioners believed affected adherence. Other variables researched were: marital status, gender, weight, age, type and duration of diabetes, socioeconomic status, occupation and education. PATIENTS: Adult diabetic patients (215) seen in the diabetic clinic of a large health maintenance organization who had their diabetes for at least 6 months. METHODS: Data were collected from interviews and medical records over a two-year period. RESULTS: Ethnicity, the major test variable, did not show a relationship to adherence. Two variables, gender and weight, showed a trend to significant relationship to adherence. Chi square and t tests were used, depending on the type of data. CONCLUSIONS: Since there is no difference in adherence between ethnic groups, standardized care protocols are warranted, since they are cost-efficient.
Adult↗
p120 Ras GTPase-activating protein interacts with Ras-GTP through specific conserved residues.
Previous structural studies of RasGAP have failed to clearly localize sites of Ras interaction to individual amino acids. Hypothesizing that sites of interaction with Ras-GTP would be conserved, 11 of the most highly conserved amino acid residues of RasGAP were changed by mutation. Each mutant protein was purified as a glutathione S-transferase catalytic domain fusion and analyzed for protein stability, Ras GTPase stimulating activity, affinity for Ras-GTP, and when possible, secondary structure. The majority of conserved positions were found to be important structurally but with no direct role in Ras interactions. However, Arg786, Lys831, and Arg925 were observed to be essential for binding to Ras-GTP but not for protein structure. RasGAP residues 890-902 (block 3A) were observed to be homologous to residues 1540-1552 of the yeast adenylyl cyclase with amino acid substitutions in both regions resulting in increased affinity for Ras. This is the first example of a conserved Ras interaction motif in distinct Ras effector proteins. Our data are supportive of a model for GAP/Ras-GTP association in which the conserved, positively charged Arg786, Lys831, and Arg925 residues form salt bridges with the conserved, negatively charged residues in the Ras effector loop.
Adenylyl Cyclases↗
Diabetes mellitus affects prostaglandin E2 levels in mouse embryos during neurulation.
The arachidonic acid cascade leading to prostaglandins has been implicated in diabetic embryopathy. Both arachidonic acid and prostaglandin E2 reverse the teratogenic effects of high glucose concentrations on neural tube development in mouse embryos in culture. Arachidonic acid supplementation also protects against diabetes-induced neural tube defects in vivo. In the present study, prostaglandin E2 was measured directly in embryos from normal and diabetic mice. In normal mice a clear developmental pattern was seen. Prostaglandin E2 levels were high during early formation of the cranial neural folds (day 8), declined during convergence and fusion of the cranial neural folds to form the neural tube (day 9), and were low after neurulation was complete (days 10 and 11). In addition, evidence in this study indicates that embryos have cyclooxygenase activity capable of generating prostaglandin E2 during a brief developmental period preceding neural tube closure. In embryos from mice made diabetic (> 13.9 mmol/l glucose) with streptozotocin, prostaglandin E2 levels were significantly lower than normal during early development of the cranial neural folds (day 8), but similar to normal after the cranial neural tube had closed (late day 9 and day 10). The findings suggest that diabetes mellitus, as ascertained by high blood glucose, promotes cranial neural tube malformations by causing a functional deficiency of prostaglandin E2 during early neurulation. Whether the altered PGE2 pattern in the embryo indicates a diabetic effect on the arachidonic acid-prostaglandin cascade in cells of the embryo or in cells of extraembryonic or maternal tissues is uncertain.
Animals↗
Social contact, social attitudes, and twin similarity.
The nature of the relationship between social contact and attitude similarly between twins was investigated using longitudinal data from a sample of Australian twins. Earlier research has suggested that social attitudes are not explained solely by shared environment; rather there are both genetic and environmental components that explain variance in social attitudes. Using three types of analyses we investigated the magnitude of the relationship and the direction of causation between attitude similarity and social contact. Longitudinal analysis of within-pair variance by level of contact suggests that attitude similarity leads to contact among the females and that similarity is both genetically and environmentally based. Analyses using a crosslag regression model suggest that similarity causes contact among MZ females. Biometrical analyses indicate differences in direction of causation for males and females. Among females, both genetic and shared environmental parameter estimates could be equated across contact groups, suggesting little relationship between contact and similarity. Among males, findings of smaller estimated heritability in the high-contact group suggest that similarity causes contact. However, an increased estimate of the contribution of shared environmental variance in the high-contact males could additionally suggest that contact leads to similarity.
Adolescent↗
Identification and antitumor activity of a reduction product in the murine metabolism of pyrazoloacridine (NSC-366140).
PURPOSE: Pyrazoloacridine (PZA) is a newly developed anticancer agent currently undergoing clinical trials. Its mode of action has not been elucidated but the presence in its chemical structure of a 5-nitro functional group and its activity against oxygen-deficient cancerous cells argue in favor of enzymatic nitro reduction as a possible pathway for its antitumor activity. In order to assess the involvement of the nitro functionality in PZA activity, as well as to determine other metabolic products, a pharmacological and chemical study of PZA was designed. METHODS: Urine and stool samples were collected from mice before and after treatment with PZA. Samples were fractionated using chromatographic methods and then evaluated using mass spectrometry (MS). One of the characterized metabolites was synthesized and tested in vitro and in vivo for anticancer activity. RESULTS: One major fraction from mouse stool was initially characterized by MS as the 5-aminopyrazoloacridine (5-APZ). This compound was chemically synthesized by catalytic hydrogenation of PZA was stabilized as the hydrochloride salt. 5-APZ was marginally cytotoxic in vitro and was inactive in vivo against a tumor cured by PZA (Panc 03). CONCLUSIONS: Bioreduction of the nitro group to an amine compound from PZA represents a pathway in the metabolic sequence of PZA. The inactivity of the chemically generated amine product does not provide conclusive evidence that this pathway is not involved in the cytotoxicity of PZA because other intermediates in the nitro reduction pathway may have a role in the activity of PZA. In particular, the hydroxylamine derivative of PZA could give answers to the involvement of this pathway in PZA cytotoxicity.
Acridines↗
Critical care of the patient with hematologic malignancy.
Patients with leukemia, lymphoma, or multiple myeloma are prone to critical illness because of the diffuse nature of their disease and the disruption of protective mechanisms. Despite high morbidity rates, a number of these patients have an excellent probability of long-term remission if supported through a crisis. Complications that cause critical illness can be categorized as related to disease or those caused by therapy. Those with unique features or management strategies for the hematologic malignancy patient and are included in this discussion include: leukostasis, disseminated intravascular coagulation, tumor lysis syndrome, respiratory failure, and typhlitis. A case study of an acutely ill, newly diagnosed patient with several of these oncologic emergencies is used to exemplify typical clinical finds and management strategies.
Adult↗
Children's methods of coping with stress: a twin study of genetic and environmental influences.
The relative importance of environmental and hereditary factors in how children cope with stress was examined. Emotion-focused, problem-focused, and additional coping variables were assessed in 44 monozygotic (MZ) and 30 dizygotic (DZ) twin pairs, aged 9-16 years. The effects of heritability, shared environment, and unshared environment were examined in structural modelling analyses. Genetic factors accounted for a majority of the reliable variance in four of seven coping variables, while effects of twins' shared environment were negligible for all but one coping variable. Environmental factors important to individual differences in coping strategies were primarily unique to each child (unshared between the twins), highlighting the importance of individual experiences in shaping coping behaviors.
Adaptation, Psychological↗
New in vitro screening model for the discovery of antileukemic anticancer agents.
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Animals↗