Progress in the development of RBC substitutes.
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Blood Substitutes↗
Biomedical subjects
J Levin
Publications and source records attributed to J Levin.
Neuropsychological dysfunction, mood disturbance, and emotional status of munitions workers.
The objective of this study was to compare the neuropsychological function, emotional status, visual function, and illness prevalence of 265 former munitions plant workers (M age = 56.7 years, M years of education = 12.07; 201 African American, 64 White) exposed to organic solvents for an average of 17.03 years with that of a group of 77 unexposed controls (M age = 51.3 years, M years of education = 13.07; 30 African American, 47 White). Neuropsychological tests were selected from the World Health Organization Neurobehavioral Core Test Battery, Wechsler Adult Intelligence Scale-III (WAIS-III), and Wechsler Memory Scale-III (WMS-III) and also included the Brief Symptom Inventory, Profile of Mood States, Beck Anxiety Inventory, and Beck Depression Inventory. Vision tests included the Lanthony d-15 color vision, the Vistech Contrast Sensitivity, and the Snellen. The exposed group showed greater deficits than the controls in verbal learning (WMS-III Logical Memory I Learning Slope and Word Lists I Recall), visuomotor tracking speed (Cancellation H, WAIS-III Digit Symbol-Coding) and psychomotor function (Dynamometer and Grooved Pegboard), and dysfunction in emotional status, illness prevalence, and visual function. African American workers reported higher levels of exposure than Whites. Exposure relations demonstrated increased neuropsychological dysfunction with increased exposure.
Adult↗
On the epidemiology of 'mysterious' phenomena.
In the field of epidemiology, research topics are favored or dismissed depending on whether respective variables under investigation are believed to exist according to current scientific theories. Unconventional independent variables or exposures, such as religiousness and spirituality, and controversial dependent variables or outcomes, such as chronic fatigue syndrome, may be considered unacceptable topics for researchers because they do not fit comfortably into the consensus clinical perspectives of mainstream medical scientists or physicians. Disapproval of research in these and other taboo areas is generally masked by claims that such studies are "pseudoscientific," despite hundreds or thousands of peer-reviewed publications on these topics. In reality, seemingly "mysterious" variables are equally as amenable to epidemiologic research as any other exposure or disease. Similarly, alternative therapies are able to be investigated using existing methods, despite claims to the contrary. Such research is vital for scientific understanding to be expanded into new areas of inquiry.
Complementary Therapies↗
Prevalence of emotional, physical and sexual abuse of women in three South African provinces.
INTRODUCTION: There is growing recognition in the ranks of the South African government that violence against women is a serious problem facing us all. Until now data on the epidemiology of violence against women in South Africa have been scanty. This report presents the findings of the first major community-based prevalence study. OBJECTIVES: To describe the prevalence of physical, sexual, financial, and emotional abuse of women. METHODS: A cross-sectional study conducted in the Eastern Cape (EC), Mpumalanga (MP) and the Northern Province (NP). The sample included one randomly selected woman aged 18-49 years living in each of 2,232 households. The sample was drawn using stratified, multistage, random methods, and 1,306 questionnaires were completed, giving a 90.3% response rate after adjusting for households without an eligible woman. RESULTS: The prevalences of ever having been physically abused by a current or ex-partner were 26.8% (EC), 28.4% (MP) and 19.1% (NP). The prevalences of abuse in the last year were 10.9% (EC), 11.9% (MP) and 4.5% (NP). The prevalences of rape were 4.5% (EC), 7.2% (MP) and 4.8% (NP). Considerable emotional and financial abuse was also reported, e.g. the prevalences of a partner having boasted about or brought home girlfriends in the previous year were 5.0% (EC), 10.4% (MP) and 7.0% (NP): The prevalences of physical abuse during a pregnancy were 9.1% (EC), 6.7% (MP) and 4.7% (NP). The proportions of abused women who were injured in the year before the survey were 34.5% (EC), 48.0% (MP) and 60.0% (NP). CONCLUSIONS: This study is the first large-scale, community-based prevalence study to be undertaken in South Africa.
Adolescent↗
The Brazilian National Health Informatics Strategy.
This paper describes the Brazilian National Strategy for the development of the national Health Informatics Infrastructure. An overall description of the use of IT in the Brazilian Health scenario is presented with emphasis on the federal initiatives by DATASUS, the informatics division of the Ministry of Health. The national health card project is discussed and the strategies to establish interoperability among systems are presented. The adopted standards and methodologies used are also discussed.
Brazil↗
Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group.
Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy. These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the management of dyslipidemia in the general population formed the general basis for our recommendations. Data on the prevalence and treatment of dyslipidemia of HIV-infected patients, implications of treatment-related dyslipidemia in other chronically ill populations, and pharmacokinetic profiles for the available hypolipidemic agents in non-HIV populations were considered. Although the implications of dyslipidemia in this population are not fully known, the frequency, type, and magnitude of lipid alterations in HIV-infected people are expected to result in increased cardiovascular morbidity. We propose that these patients undergo evaluation and treatment on the basis of existing guidelines for dyslipidemia, with the caveat that avoidance of interactions with antiretroviral agents is paramount.
Acquired Immunodeficiency Syndrome↗
Transfusion of soluble hemoglobin.
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Anemia, Hemolytic, Autoimmune↗
Gravity waves, chaos, and spinning compact binaries
Spinning compact binaries are shown to be chaotic in the post-Newtonian expansion of the two-body system. Chaos by definition is the extreme sensitivity to initial conditions and a consequent inability to predict the outcome of the evolution. As a result, the spinning pair will have unpredictable gravitational waveforms during coalescence. This poses a challenge to future gravity wave observatories which rely on a match between the data and a theoretical template.
Journal Article↗
Institutional variability in red blood cell conservation practices for coronary artery bypass graft surgery. Institutions of the MultiCenter Study of Perioperative Ischemia Research Group.
OBJECTIVE: To assess whether substantial institutional variability exists in red blood cell conservation practices associated with coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized patient enrollment and data collection. SETTING: Twenty-four U.S. academic institutions participating in the Multicenter Study of Perioperative Ischemia. PARTICIPANTS: A well-defined subset of primary CABG surgery patients (n = 713) expected to be at low risk for bleeding and exposure to allogeneic transfusion. INTERVENTIONS: None (observational study). MEASUREMENTS AND MAIN RESULTS: Frequency of use of red blood cell conservation techniques was determined among institutions. Correlation was determined between use of each technique and transfusion of allogeneic red blood cells and between use of each technique and median institutional blood loss. Significant variability (p < 0.01) was detected in institutional transfusion practice with respect to the use of predonated autologous whole blood, normovolemic hemodilution, red cell salvage, and reinfusion of shed mediastinal blood. The frequency of institutional use of these techniques was not associated with allogeneic transfusion (r2 < 0.15) or blood loss (r2 < 0.10) in the low-risk population of patients examined. CONCLUSIONS: Institutions vary significantly in perioperative blood conservation practices for CABG surgery. Further study to determine the appropriate use of these techniques is warranted.
Blood Loss, Surgical↗
Clinical development of eniluracil/fluorouracil: an oral treatment for patients with solid tumors.
Eniluracil (776C85, GW776) inactivates dihydropyrimidine dehydrogenase (DPD), the principal enzyme of 5-fluorouracil (5-FU) catabolism. Inactivation of DPD eliminates a potential mechanism for tumor 5-FU resistance and permits achievement of reliable and predictable pharmacokinetics following oral 5-FU administration. Eniluracil/5-FU has demonstrated efficacy as monotherapy in patients with a variety of solid tumors when given on a 5 or 28-day dosing schedule. The primary and dose-limiting toxicity is myelosuppression with the 5-day schedule and diarrhea with the 28-day schedule. The frequency of hand-foot syndrome is minimal with either schedule. Phase III pivotal registration-directed studies with eniluracil/5-FU given by the 28-day schedule are ongoing or planned for the near future in patients with advanced colorectal, breast and pancreatic cancer.
Administration, Oral↗
A multicenter phase II study of a five-day regimen of oral 5-fluorouracil plus eniluracil with or without leucovorin in patients with metastatic colorectal cancer.
PURPOSE: To evaluate the safety and efficacy of a five-day regimen of oral 5-fluorouracil (5-FU) plus eniluracil (776C85) in patients with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Seventy-five patients with metastatic CRC that was previously untreated or refractory to 5-FU-leucovorin (LV) were enrolled and divided into two strata based upon their treatment history. Twenty-four had not previously received chemotherapy or had received adjuvant chemotherapy that ended > 6 months prior to enrollment on study (previously untreated stratum). Fifty-one patients had disease refractory to intravenous (i.v.) 5-FU-LV (previously treated stratum). All patients received seven consecutive daily doses of eniluracil (20 mg/day) with once daily oral 5-FU given on days 2-6, repeated every four weeks. One-half of the patients in each stratum also received 50 mg/day oral LV on days 2-6. The 5-FU dose was 25 mg/m2 when administered without LV and 20 mg/m2 when administered with LV. RESULTS: Partial response (PR) was noted in 2 of 12 patients receiving eniluracil-5-FU and in 3 of 12 patients receiving eniluracil-5-FU-LV in the previously untreated stratum. No responses were observed in the refractory disease stratum, however, 15 patients (30%) demonstrated stable disease over 2-18+ courses of therapy. Non-hematologic toxicities were mild; only 7% of patients experienced grade 3 diarrhea. Myelosuppression was frequent and dose limiting. Neutropenic sepsis was reported in 13.5% of patients. CONCLUSIONS: Eniluracil with 5-FU administered orally with or without LV on a five-day schedule is active and well tolerated when given as primary therapy to patients with metastatic CRC.
Administration, Oral↗
Multicenter phase II study to evaluate a 28-day regimen of oral fluorouracil plus eniluracil in the treatment of patients with previously untreated metastatic colorectal cancer.
PURPOSE: To determine the efficacy of fluorouracil (5-FU) plus eniluracil when administered to patients with previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: In this single-arm phase II study, patients with previously untreated metastatic colorectal cancer received oral eniluracil plus 5-FU (10:1 dose ratio), at 5-FU doses of 1.00 mg/m(2) or 1.15 mg/m(2) twice daily (every 12 hours) for 28 consecutive days repeated every 5 weeks (one cycle). Treatment continued until there was documented disease progression or unacceptable toxicity. RESULTS: Thirty and 25 patients were enrolled at a starting dose of 1.00 mg/m(2) and 1.15 mg/m(2), respectively. Fourteen (25%) of 55 patients (95% confidence interval, 15% to 39%) had a partial response, and 20 patients (36%) had stable disease. The median durations of the partial responses and stable disease were 23.9 weeks (range, 12.3 to 52.1+ weeks) and 24.1 weeks (range, 17.1 to 55.6+ weeks), respectively. The median durations of progression-free and overall survival were 22.6 weeks (range, 21.0 to 29.0 weeks) and 59 weeks (range, 4 to 84+ weeks), respectively. The response rate in the 1.15 mg/m(2)-dose group was similar to the 1.00 mg/m(2)-dose group (28% v 23%, respectively). Severe (grade 3/4) nonhematologic treatment-related toxicity included diarrhea (nine patients), nausea/vomiting (one patient each), mucositis (two patients), and anorexia (one patient). Severe hematologic toxicities were rare. At the 1.15 mg/m(2)-dose level, two patients exhibited grade 3 granulocytopenia, and two patients had grade 3 anemia. CONCLUSION: The response rate with oral 5-FU plus eniluracil is comparable with that observed with infusional 5-FU or bolus 5-FU and leucovorin. The toxicity profile of this oral regimen is acceptable for use in an outpatient home-based setting.
Administration, Oral↗
The effects of arsenic trioxide (As2O3) on human megakaryocytic leukemia cell lines. With a comparison of its effects on other cell lineages.
Arsenic trioxide (As2O3) has been demonstrated to be effective for the treatment of acute promyelocytic leukemia (APL) and to inhibit proliferation and produce apoptosis in the APL cell line NB4. The effect of this newly utilized chemotherapeutic agent on other lineages is currently under study to evaluate its efficacy for the treatment of other human malignancies and myeloproliferative syndromes. A recent study described the effects of As2O3 upon viability, proliferation, and induction of apoptosis in four different megakaryocytic leukemia cell lines. At pharmacological concentrations (0.5-2 microM) As2O3 selectively inhibits growth and causes apoptosis in the megakaryocytic leukemia cell lines HEL, Meg-01, UT7 and M07e. Pertinently, these concentrations of As2O3 resulted in identical changes in the characteristics of the APL cell line NB4, suggesting that As2O3 could produce its effects in both cellular lineages via a common mechanism of action. Various mechanisms have been proposed for the As2O3-induced changes in NB4 (including modulation of promyelocytic leukemia proteins (PML) and Bcl-2, modification of the glutathione redox system, caspase activation, and cell cycle arrest) and are currently under investigation in the megakaryocytic leukemia cell lines. Recent preliminary results indicate that As2O3 downregulates Bcl-2 expression and induces cell cycle arrest in megakaryocytic cell lines. The use of As2O3 for the treatment of malignant megakaryocytic disorders also has been considered. The in vitro effects of As2O3 on a chronic megakaryocytic proliferative disorder. i.e., Essential Thrombocythemia (ET), have been analyzed and megakaryocyte progenitors have shown an unexpectedly higher resistance to As2O3, in comparison to normal megakaryocyte colony-forming cells. The effects of As2O3 on ET and other megakaryocytic disorders need to be fully examined, in order to determine the clinical efficacy of As2O3 in the treatment of syndromes affecting the megakaryocytic lineage.
Antineoplastic Agents↗
Randomised controlled trial of the efficacy of misoprostol used as a cervical ripening agent prior to termination of pregnancy in the first trimester.
BACKGROUND: Misoprostol is being used increasingly in clinical practice for cervical ripening in first-trimester abortions, but because of lack of good evidence of its effectiveness, administration consensus has not been reached on dosage, route of administration, time of administration pre-operatively and gestational age group. In this study we tested the hypothesis that self-administration of 600 micrograms vaginal misoprostol is feasible and when used 2-4 hours pre-operatively results in sufficient cervical dilatation to make suction curettage easier. METHODS: A double-blind, randomised, placebo-controlled trial was undertaken. Two hundred and seventy-eight women scheduled for termination of pregnancy of up to 12 weeks' duration by manual vacuum aspiration were assigned to receive either 600 micrograms misoprostol pre-operatively, or placebo. The achievement of 'satisfactory' (> or = 7 mm) baseline cervical dilatation after 2-4 hours was evaluated as the primary outcome. Secondary outcome measurements included ease and duration of the procedure. Side-effects such as pre-operative bleeding, gastro-intestinal complaints and pain as well as adverse events were noted in all cases. FINDINGS: Self-administration of vaginal misoprostol was successful in all women and 273 women were evaluated for main end-points. A significantly larger proportion of patients in the treatment group reached cervical dilatation of > or = 7 mm (67.3% v. 30.9%, P < 0.0001). The side-effects were minimal and comparable in the two groups. In the treatment group the mean procedure duration was significantly shorter (220 seconds v. 321 seconds, P = 0.0013) and the procedure was more likely to be rated by the operator as 'easy' (81.8% v. 63.3%, P = 0.0082). This resulted in a significant reduction in treatment failure in the < 70-day gestation group (5.0% v. 14.7%, P = 0.005). CONCLUSION: It is feasible, safe and effective for 600 micrograms misoprostol to be self-administered vaginally 2-4 hours pre-operatively for cervical priming prior to manual vacuum aspiration. Further research is needed to establish optimal use in the first trimester and to determine patient acceptance.
Abortifacient Agents, Nonsteroidal↗
1999 HIV surveillance result--little grounds for pessimism.
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Acquired Immunodeficiency Syndrome↗
Bacterial endotoxin (lipopolysaccharide) stimulates the rate of iron oxidation.
Bacterial endotoxin (lipopolysaccharide) has affinity for a number of cations, including iron. Previous investigations have demonstrated that lipopolysaccharide can affect the oxidation rate of iron; heme-bound ferrous iron in hemoglobin is oxidized to ferric iron when hemoglobin binds lipopolysaccharide. In the present study, we directly examined the interaction between lipopolysaccharide and iron. Lipopolysaccharide caused a concentration-dependent increase in the rate of iron oxidation, with up to a 23-fold increase in oxidation in the presence of 200 microg/ml Escherichia coli lipopolysaccharide. This effect was seen both with several carbohydrate-rich smooth lipopolysaccharides and also with carbohydrate-poor rough lipopolysaccharide. Extensively deacylated rough lipopolysaccharide had no effect, suggesting a role of the fatty acid components of lipopolysaccharide in this process. Purified lipid A produced inconsistent results: some preparations stimulated iron oxidation and others did not. A series of sugars, starches and a preparation of purified O-chain polysaccharide (the carbohydrate portion of the lipopolysaccharide macro-molecule) had no effect on the rate of iron oxidation, whereas phospholipid-enriched brain tissue extracts (similar to the lipid A component of lipopolysaccharide) stimulated oxidation. We conclude that the lipid moiety of bacterial lipopolysaccharide is responsible for the stimulation of iron oxidation. This process may contribute to the ability of lipopolysaccharide to cause oxidation of heme-bound iron in hemoglobin.
Carbohydrates↗
Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2.
Expression of the p45 subunit of transcription factor NF-E2 is restricted to selected blood cell lineages, including megakaryocytes and developing erythrocytes. Mice lacking p45 NF-E2 show profound thrombocytopenia, resulting from a late arrest in megakaryocyte differentiation, and a number of red blood cell defects, including anisocytosis and hypochromia. Here we report results of studies aimed to explore the pathophysiology of these abnormalities. Mice lacking NF-E2 produce very few platelet-like particles that display highly disorganized ultrastructure and respond poorly to platelet agonists, features consistent with the usually lethal hemorrhage in these animals. Thrombocytopenia was evident during fetal life and was not corrected by splenectomy in adults. Surprisingly, fetal NF-E2-deficient megakaryocyte progenitors showed reduced proliferation potential in vitro. Thus, NF-E2 is required for regulated megakaryocyte growth as well as for differentiation into platelets. All the erythroid abnormalities were reproduced in lethally irradiated wild-type recipients of hematopoietic cells derived from NF-E2-null fetuses. Whole blood from mice lacking p45 NF-E2 showed numerous small red blood cell fragments; however, survival of intact erythrocytes in vivo was indistinguishable from control mice. Considered together, these observations indicate a requirement for NF-E2 in generating normal erythrocytes. Despite impressive splenomegaly at baseline, mice lacking p45 NF-E2 survived splenectomy, which resulted in increased reticulocyte numbers. This reveals considerable erythroid reserve within extra-splenic sites of hematopoiesis and suggests a role for the spleen in clearing abnormal erythrocytes. Our findings address distinct aspects of the requirements for NF-E2 in blood cell homeostasis and establish its roles in proper differentiation of megakaryocytes and erythrocytes.
Anemia↗
Interrupting HAART; Hydroxyurea; five+ drug therapy - report from the RIGHT Conference.
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Anti-HIV Agents↗