PubMed Health⌕ Search

Biomedical subjects

B Newton

Publications and source records attributed to B Newton.

At least 19 recordsLinked to original sources
PubMed2006

Novel bacterial acetyl coenzyme A carboxylase inhibitors with antibiotic efficacy in vivo.

The pseudopeptide pyrrolidinedione antibiotics, such as moiramide B, have recently been discovered to target the multisubunit acetyl coenzyme A (acetyl-CoA) carboxylases of bacteria. In this paper, we describe synthetic variations of each moiety of the modularly composed pyrrolidinediones, providing insight into structure-activity relationships of biochemical target activity, in vitro potency, and in vivo efficacy. The novel derivatives showed highly improved activities against gram-positive bacteria compared to those of previously reported variants. The compounds exhibited a MIC(90) value of 0.1 microg/ml against a broad spectrum of Staphylococcus aureus clinical isolates. No cross-resistance to antibiotics currently used in clinical practice was observed. Resistance mutations induced by pyrrolidinediones are exclusively located in the carboxyltransferase subunits of the bacterial acetyl-CoA carboxylase, indicating the identical mechanisms of action of all derivatives tested. Improvement of the physicochemical profile was achieved by salt formation, leading to aqueous solubilities of up to 5 g/liter. For the first time, the in vitro activity of this compound class was compared with its in vivo efficacy, demonstrating a path from compounds weakly active in vivo to agents with significant efficacy. In a murine model of S. aureus sepsis, the 100% effective dose of the best compound reported was 25 mg/kg of body weight, only fourfold higher than that of the comparator molecule linezolid. The obvious improvements achieved by chemical derivatization reflect the potential of this novel antibiotic compound class for future therapy.

Acetamides↗
PubMed2001

A stream visual assessment protocol (SVAP) for riparian landowners.

A user-friendly Stream Visual Assessment Protocol (SVAP) was recently developed in a joint effort by the Natural Resources Conservation Service (NRCS) of the U.S. Department of Agriculture and the University of Georgia. SVAP was designed to be an introductory screening-level assessment method for people unfamiliar with stream assessments. It was designed for use by NRCS field staff who work with agricultural landowners. NRCS is in a key position to influence conservation practices since the organization works with private stakeholders, maintaining more than 2000 field offices throughout the U.S. with a central office in each state. The SVAP measures a maximum of 15 elements and is based on visual inspection of the physical and biological characteristics of instream and riparian environments. Each element is assigned a numerical score relative to reference conditions and an overall score for the stream reach is calculated. A qualitative description of the stream reach is made based on overall numerical score. While SVAP is not intended to replace more robust stream assessment protocols, it provides quick and reliable information for use in NRCS farm assistance programs. It is also an educational tool through which landowners can learn about conservation of aquatic resources. An abridged copy of SVAP is attached as an appendix to this article and the complete document can be found on the web at http://www.ncg.nrcs.usda.gov/tech_notes.html.

Agriculture↗
PubMed2001

Fire incidents involving regulators used in portable oxygen systems.

OBJECTIVES: To address the causes and prevention of fire incidents involving aluminum bodied oxygen regulators used by firefighters or emergency medical technicians. METHODS: The National Institute for Occupational Safety and Health, the United States Food and Drug Administration, and an independent forensic investigator examined several incidents involving injury to firefighters and emergency medical technicians to determine why regulators in these incidents flashed. RESULTS: Data and test results from investigations revealed that aluminum was a contributing factor, and there were a number of safe handling techniques which firefighters and emergency medical technicians could use to reduce the risk of regulator fires. A provisional test method was proposed by the American Society for Testing and materials (ASTM) in late 2000 to identify designs that would have a propensity for flashing. Results of the test method show good correlation with actual fire incidents. CONCLUSION: Development of the ASTM standard and associated testing will be helpful to oxygen regulator designers to design safer oxygen regulator systems. As well, there are a number of additional safe handling procedures that firefighters and emergency medical technicians can follow to reduce the risk of a regulator fire.

Accidents, Occupational↗
PubMed1992

Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy.

PURPOSE: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. PATIENTS AND METHODS: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). RESULTS: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. CONCLUSION: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.

Adult↗
PubMed1992

A dose-escalation study of carboplatin/cyclophosphamide/etoposide along with autologous bone marrow or peripheral blood stem cell rescue.

Twenty patients have received 21 courses of high-dose cyclophosphamide (6 g/m2 over 4 days), etoposide (1,800 mg/m2 over 3 days), and carboplatin (800 to 1,600 mg/m2 by continuous infusion over 96 hours) and autologous bone marrow or peripheral blood stem cell rescue. The maximum tolerated dose of this regimen included these doses of cyclophosphamide and etoposide with a total of 1,600 mg/m2 carboplatin. Acute renal failure was the dose-limiting toxicity and, at the maximum tolerated dose, was observed in two patients of 14 evaluable courses. Nonhematologic toxicity was otherwise modest, and the overall response rate was 70% in patients with a wide variety of solid hematologic neoplasms.

Acute Kidney Injury↗
PubMed1991

Can managed care reduce employers' retiree medical liability?

The Financial Accounting Standards Board (FASB) has forced U.S. companies to look squarely at their current retiree health obligations and their future commitments. Accounting Statement No. 106 (FAS 106) requires employers to accrue liabilities for retiree health benefits during employees' active service, rather than record the costs as benefits are paid. Employers are scrambling to find ways to reduce the statement's effect on corporate balance sheets. While managed health care has been increasingly employed to control benefit costs in active employee health plans, it has not been as popular in retiree plans. This article reviews important demographic and health trends in the retiree population and summarizes employers' early responses to FAS 106. It explores why managed health care has thus far played a limited role in reducing employers' postretirement medical liability, and offers insight into how that role could be increased in the future.

Accounting↗
PubMed1986

Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation.

In an attempt to prevent primary cytomegalovirus infection after marrow transplantation, we randomly assigned 97 patients who were seronegative for antibody to cytomegalovirus before transplantation to receive one of the following: (1) both intravenous cytomegalovirus immune globulin and seronegative blood products (23 patients); (2) seronegative blood products alone (28 patients); (3) globulin alone (22 patients); or (4) neither treatment (24 patients). Patients not assigned to receive seronegative blood products received unscreened blood products from random donors. The incidence of cytomegalovirus infection according to study group among patients in the study for at least 62 days was 5 percent, 13 percent, 24 percent, and 40 percent, respectively. Among 57 patients with seronegative marrow donors, those who received seronegative blood products had significantly less infection (1 of 32) than those who received standard blood products (8 of 25, P less than 0.007). In contrast, the use of seronegative blood products did not appear to prevent cytomegalovirus infection among patients with seropositive marrow donors. The possibility that cytomegalovirus immune globulin as used in this study can prevent cytomegalovirus infection or ameliorate cytomegalovirus disease was not confirmed, and it cannot be recommended for routine use without additional study.

Adolescent↗
PubMed1985

Tough love: help for parents with troubled teenagers--reorganizing the hierarchy in disorganized families.

There has been confusion among professionals and the public about the purpose and appropriateness of the "tough love" approach to parenting troubled teenagers. This article addresses some of the questions and tries to clarify misconceptions about the tough love approach. A description of a model "Tough Love" training/support group and results of parent feedback surveys are included to provide a clearer picture of the goals and effectiveness of tough love.

Adolescent↗
PubMed1984

Acyclovir treatment of varicella-zoster virus infection in the compromised host.

Forty marrow transplant patients were treated with acyclovir for varicella-zoster virus infection. Median duration of virus positivity and of new lesion formation was 2.1 and 2.2 days, and pustulation , crusting, and healing occurred at medians of 3.5, 8, and 28 days, respectively. Acute pain ceased at a median of 7 days, though seven patients had later recurrence of pain and eight had pain that persisted for more than 28 days. Three patients had recurrence of infection within 4 days after the end of treatment and were successfully treated in each case with a second course of acyclovir. Side effects were minimal. These data compare favorably with published data both from the treatment of normal persons with acyclovir and treatment of normal persons with acyclovir and treatment of immunocompromised patients with vidarabine, and they indicate that acyclovir is safe and effective for the treatment of varicella-zoster virus infection in the severely immunocompromised host.

Acyclovir↗
PubMed1984

Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation.

Oral acyclovir was found to be safe and effective for the prevention of herpes simplex virus reactivation after marrow transplantation in a double-blind, placebo-controlled trial. Acyclovir or placebo was administered to 49 patients for 5 weeks beginning 1 week before transplantation: 5 of 24 patients receiving acyclovir developed herpes simplex virus infection during prophylaxis, compared to 17 of 25 patients receiving placebo (p less than 0.01). The median time to first virus reactivation was significantly longer among patients receiving acyclovir (78 days versus 9 days after transplant, p = 0.006). The effect was even more pronounced when the analysis was adjusted for drug compliance: Among patients taking a minimum of 40% of their prescribed drug, acyclovir was 96% virologically effective and 100% clinically effective during the period of administration. Acyclovir use was also associated with significantly more rapid marrow engraftment in patients receiving methotrexate. No virus resistant to acyclovir was isolated. Oral acyclovir provides effective prophylaxis against reactivation of herpes simplex virus among severely immunosuppressed patients able to take orally administered drugs.

Acyclovir↗
PubMed1983

Treatment of cytomegaloviral pneumonia with high-dose acyclovir and human leukocyte interferon.

Thirteen recipients of bone marrow transplants were given high-dose acyclovir and alpha-interferon (Cantell interferon) for the treatment of biopsy-proven cytomegaloviral pneumonia. Three patients survived. Doses of acyclovir between 500 and 1,000 mg/m2 of body surface area (peak plasma levels, 7-86 micrograms/ml) and doses of interferon between 2 X 10(4) and 40 X 10(4) units/kg per day (peak serum levels, 5-608 units/ml) were given. No consistent antiviral effect was seen despite the large doses employed. Possible marrow toxicity associated with this regimen occurred in five patients, neurologic symptoms in two, and nephrotoxicity in one. Thus, treatment with high-dose acyclovir plus alpha-interferon was moderately toxic but ineffective against cytomegaloviral pneumonia after bone marrow transplantation.

Acyclovir↗
PubMed1983

Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation.

In an effort to prevent cytomegalovirus infection among seronegative patients having marrow transplants, a globulin with high antibody levels against cytomegalovirus was given before and for 11 weeks after transplantation in a randomized trial. Among 36 patients who received no prophylactic granulocyte transfusions, globulin recipients had significantly fewer infections than controls (2 of 17 versus 8 of 19, p = 0.05 by Fisher's exact test and p = 0.03 by Mantel-Cox test). Conversely, infection rates were high and unchanged by globulin use among patients who received granulocytes from seropositive donors (7 of 8 recipients versus 6 of 7 controls). The lack of effect of the globulin among patients receiving transfusions of granulocytes from seropositive donors may suggest that the dose of antibody was insufficient or that antibody is ineffective against virus transmitted in granulocytes. We conclude that cytomegalovirus infection can be prevented by immunoprophylaxis in seronegative patients having marrow transplants who are not given granulocyte transfusions.

Adolescent↗
PubMed1982

A temperature-dependent choice in cell differentiation.

Ascension of the cell mass during culmination was observed to be temperature-sensitive in strain HH31 of the cellular slime mold Dictyostelium discoideum. A sequence of additional developmental abnormalities was also observed both preceeding and succeeding culmination. Slugs reared at the restrictive temperature (27 degrees C), in contrast to those reared at the permissive temperature (22 degrees C), were deficient in the expression of six prespore markers and elevated in the production of four prestalk markers. Following attempted culmination at the restrictive temperature, the majority of cells were stalk cells according to fluorescence, phase contrast, electron microscopic, biochemical, and plating efficiency criteria. These findings were correlated with a general diminution of staining of slug cell Membrane extracts on polyacrylamide gels with FITC-wheat germ agglutinin. The effect of the higher temperature was readily reversible prior to terminal differentiation. An interdependence of several of the changes was suggested by the observation that in two derivative strains the temperature-dependence of these changes was coordinately altered. In summary, a large fraction of the slug cells of HH31 appear to be temperature-dependent in their choice of pathways of cell differentiation, this change is related to a modification of the cell surface, and the choice made in the slug is remembered by cells as they terminally differentiate.

Cell Differentiation↗
PubMed1982

Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation: a double-blind trial.

Acyclovir, a new antiviral agent, was compared to a placebo in a randomized double-blind trial of treatment for culture-proven herpes simplex virus infection after marrow transplantation. Patients received either intravenous acyclovir at 750 mg/m2 body surface area per day or a placebo for 7 days. Thirteen of 17 patients given acyclovir had a beneficial response as compared with two of 17 given the placebo (p less than 0.01). The duration of positive cultures was shorter among acyclovir recipients (3 versus 17 days, p less than 0.00005). Also shorter were the median days to resolution of pain (10 versus 16 days, p = 0.03), to crusting of lesions (7 versus 14 days, p = 0.01), and to total healing (14 versus 28 days, p = 0.03). No acyclovir toxicity was observed. Recurrent infection was common. Acyclovir provided significant antiviral and clinical efficacy without toxicity in highly immunosuppressed patients but had no effect on virus latency.

Acyclovir↗
PubMed1975

The Middleton outbreak: 125 cases of foodborne salmonellosis resulting from cross-contaminated food items served at a picnic and a smorgasbord.

One hundred and twenty-five of 173 people who ate at a picnic and/or a smorgasbord prepared by a bar-restaurant in a Midwestern town in September 1973 developed diarrhea, abdominal cramps, and other symptoms 23 hours (median time) later. Eleven were hospitalized. Stool cultures from 18 ill individuals grew Salmonella infantis, Salmonella agona, and Salmonella schwarzengrund. Stool cultures from 5 of 8 restaurant employees grew S. infantis or S. agona. Cultures of remaining foods and food-contact surfaces were negative. Food-specific attack rates, based on interviews with 121 eaters, implicated potato salad and chicken dressing as vehicles of transmission, both likely contaminated when prepared in pans that shortly before contained uncooked, chicken pieces suspected to have harbored salmonellae. Chickens were eventually traced to 3 farms where feed samples were found to contain Salmonella typhimurium and Salmonella cubana, raising the possibility that other feed samples may have contained the serotypes responsible for the outbreak. The main control measure was temporarily closing the food service, which was to have catered a large church picnic the next day. The outbreak had an economic impact estimated at $28,733.

Adult↗
PubMedDate not supplied

Cytomegalovirus-seronegative blood components for the prevention of primary cytomegalovirus infection after marrow transplantation. Considerations for blood banks.

The authors report 2.5 years' experience with the use of cytomegalovirus (CMV)-seronegative blood components for the prevention of primary CMV infection after allogeneic marrow transplantation from seronegative marrow donors to 104 CMV-seronegative patients. Patients and blood donors were screened for CMV-seronegativity by a combination of passive latex agglutination, complement fixation, and indirect hemagglutination CMV antibody screening methods. Changes in blood banking procedures necessary to provide CMV-seronegative components are detailed. Providing CMV-seronegative components was a considerable undertaking; a mean, per patient, of 19 units of red cells and 105 units of platelets was required. Twenty percent of the platelet support was provided by family members and 80 percent by volunteer donors. CMV-infection was eliminated in all but one patient not considered infected at the time of transplantation. The capability to provide CMV-seronegative components depends on an adequate supply of seronegative donors, a sensitive and practical screening method for CMV antibody, a major commitment by the blood bank, and close communication between the blood bank and the patients' physicians.

Antibodies, Viral↗
PubMedDate not supplied

Retention indices and dual capillary gas chromatography for rapid identification of sedative hypnotic drugs in emergency toxicology.

Recent advances in capillary column technology and gas chromatographic instrumentation allow the reproducible qualitative and semiquantitative determination of drugs in biological samples. A simple, cost-effective, and time saving method is described that utilizes a retention index library for drug identification in emergency toxicology. Samples need not be derivatized because of the inertness of the fused silica capillary system. Dual columns of different polarity are utilized to identify and simultaneously confirm results of biological drug extracts. A summary of the BASIC program used for retention index calculation and library search is included. Results from twenty double blind split specimen analyses are reported.

Body Fluids↗