PubMed Health⌕ Search

Biomedical subjects

M Boyd

Publications and source records attributed to M Boyd.

At least 19 recordsLinked to original sources
PubMed1992

Hypoxia-selective antitumor agents. 6. 4-(Alkylamino)nitroquinolines: a new class of hypoxia-selective cytotoxins.

A series of isomeric 4-[[3-(dimethylamino)propyl]amino]nitroquinolines has been synthesized and evaluated as hypoxia-selective cytotoxins and as radiosensitizers of hypoxic cells. The compounds showed widely-differing hypersensitivity factors (ratios of cytotoxicity against wild-type and repair-deficient mammalian cells). Many compounds showed oxygen-sensitive bioreduction resulting in DNA alkylation, while others show oxygen-insensitive modes of action. Of the nitro isomers studied, the 5-nitro showed the greatest hypoxic selectivity. A series of ring-substituted analogues were then prepared, in an effort to lower its reduction potential of -286 mV. Structure-activity studies showed that the effects of substitution on reduction potential were complex, being mediated by electronic and steric effects on the nitro group, as well as by effects on quinoline pKa. Two compounds of lower reduction potential, the 3- and 8-methyl analogues, showed improved selectivity (47- and 60-fold in a clonogenic assay). These two compounds also showed the highest "in vitro therapeutic indices" of the series as hypoxic cell radiosensitizers. Despite these favorable in vitro properties, neither compound had activity against hypoxic cells in SCCVII tumors when administered at 60% of the MTD.

Animals↗
PubMed1992

Potential antitumor agents. 64. Synthesis and antitumor evaluation of dibenzo[1,4]dioxin-1-carboxamides: a new class of weakly binding DNA-intercalating agents.

A series of substituted dibenzo[1,4]dioxin-1-carboxamides has been synthesized and evaluated for in vitro and in vivo antitumor activity. The required substituted dibenzo[1,4]dioxin-1-carboxylic acids were prepared by a variety of methods. No regiospecific syntheses were available for many of these, and separation of the mixtures of regioisomers obtained was sometimes difficult. The dibenzo[1,4]dioxin-1-carboxamides are active against wild-type P388 leukemia in vitro and in vivo, with structure-activity relationships resembling those for both the acridine-4-carboxamide and phenazine-1-carboxamide series of DNA-intercalating antitumor agents. In all three series, substituents placed peri to the carboxamide sidechain (the 5-position in the acridines, and the 9-position in the phenazines and dibenzo[1,4]dioxins) enhance activity and potency. The 9-chlorodibenzodioxin-1-carboxamide was also curative against the remotely sited Lewis lung carcinoma. Several of the compounds showed much lower levels of cross-resistance to the P388/AMSA line than classical DNA-intercalating agents, which suggests that their primary mechanism of action may not be via interference with topoisomerase II alpha. This is of interest with regard to the development of drugs to combat resistance mechanisms which arise by the expression of the topo II beta isozyme.

Animals↗
PubMed1992

The region of the envelope gene of human immunodeficiency virus type 1 responsible for determination of cell tropism.

Different isolates of human immunodeficiency virus type 1 (HIV-1) vary in the cell tropisms they display, i.e., the range of cell types in which they are able to establish a productive infection. Here, we report on the phenotypes of recombinants between two molecularly cloned strains of HIV-1. Our results prove that the envelope glycoprotein gp120 is solely responsible for the difference in cell tropism between the two parental isolates and that no other genes or sequences are involved in determining the cell tropism of these strains. The region of the envelope involved in the determination of cell tropism includes sequences which encode the V3 loop of gp120. Control of cell tropism by this region of the virus env gene is a general phenomenon which applies to many different HIV-1 isolates.

Amino Acid Sequence↗
PubMed1992

Education in the elderly. Adapting and evaluating teaching tools.

1. The patient's Bill of Rights documents the rights of patients to be informed of their illness, health, and treatment. 2. The use of appropriate teaching tools can significantly increase learning, especially if the tools are modified to accommodate normal aging changes. 3. An appropriate teaching tool is a critical component to the learning success of the elderly. 4. With aging changes that result in loss of short-term memory, a teaching tool may make the difference between short-term learning and long-term success.

Aged↗
PubMed1992

Emergency room resuscitative thoracotomy: when is it indicated?

This study was designed to examine the results of emergency room resuscitative thoracotomy (ERRT) and to formulate cost-effective indications for this procedure. A retrospective study was performed of 28 patients who had ERRT at St. Elizabeth Hospital Medical Center, Youngstown, Ohio, during the 4 years from July 1985 through June 1989. The prognostic factors analyzed included mechanism and site of injury, signs of life (SOL), vital signs (VS), age, gender, and prehospital care. The overall survival rate of ERRT was 7% (2 of 28 patients). The survival rate was 18% (2 of 11 patients) with penetrating trauma, and 0% (none of 17 patients) with blunt trauma. The best survival rate was 66% in the subgroup of patients with penetrating trauma and SOL present at the scene and in the emergency room (ER), (two of three patients). Our observations were combined with those of 23 studies from the literature involving 2294 trauma patients who had ERRT. Using meta-analysis, the survival rate was 11% overall. Improved survival was noted for patients with penetrating trauma compared with patients with blunt trauma (14% vs. 2%, p < 0.01). There were no survivors in the group of patients with no SOL at the scene, and there were no neurologically intact survivors among blunt trauma patients with no SOL upon arrival at the ER. An algorithm based on mechanism of injury and presence or absence of SOL at the scene and in the ER is proposed. This algorithm would decrease the number of ERRTs performed by 41% without decreasing the number of neurologically intact survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Potential antitumor agents. 63. Structure-activity relationships for side-chain analogues of the colon 38 active agent 9-oxo-9H-xanthene-4-acetic acid.

A series of 16 analogues of the solid tumor active compound 9-oxo-9H-xanthene-4-acetic acid (XAA), with variations in the acetic acid side chain, have been prepared and evaluated for their ability to cause early haemorrhagic necrosis of colon 38 tumors in mice. The results extend the previous SAR for this class and confirm the necessity for a carboxylic acid group in a fixed disposition with respect to the xanthenone chromophore. None of the compounds showed superior potency to XAA itself, with virtually all alterations in the nature of the anionic center or its geometry with respect to the chromophore greatly reducing or abolishing activity. However, alpha-methylation of the side chain was permissible, and the two enantiomers of 5-methyl-alpha-methyl-XAA were separated and tested. Both were active, but the S-(+) enantiomer was much more dose-potent than the R-(-) enantiomer, in both the in vivo tumor necrosis assay and an in vitro assay measuring the stimulation of nitric oxide production by macrophages. This suggests that the enantiomers have different intrinsic activities, rather than differing in their vivo metabolism.

Animals↗
PubMed1991

Pyrazole analogues of the bispyrrolecarboxamide anti-tumour antibiotics: synthesis, DNA binding and anti-tumour properties.

Four bispyrazole compounds have been prepared as potentially more stable analogues of the DNA minor groove binding polypyrrole compounds netropsin and distamycin, which are susceptible to oxidative breakdown. These compounds bind less strongly to DNA, and show much lower specificity for binding to AT-rich DNA sequences in comparison with distamycin. N.m.r. studies show that two of these compounds cause a downfield shift of the DNA imino proton resonances on interaction with the oligonucleotide d(ATATATATAT)2, suggesting that these isomers can adopt low-energy conformations similar to that shown by distamycin in its DNA minor groove binding site. The benzoic acid mustard analogue of one of the minor groove binding bispyrazoles was prepared, and showed in vitro cytotoxicity comparable with that of the previously-reported distamycin mustard, but only a low level of activity in vivo.

Amides↗
PubMed1990

NMR studies of configuration and tautomeric equilibria in nitroacridine antitumor agents.

The solution configurations of the 1-nitroacridine nitracrine (a clinically used anticancer agent and experimental hypoxia-selective cytotoxin) and its nitro isomers were determined, an both free bases in CDCl3 and as monocations (chromophore free base) and dications in D2O, by high-resolution proton magnetic resonance spectroscopy. The free bases of the 1-, 2-, and 3-nitro isomers exist in the aminoacridine configuration in CDCl3, while the 4-nitro isomer appears to exchange slowly between the aminoacridine and iminoacridan configurations. As cations at pH 2 in D2O, all four isomers exist in the aminoacridine configuration. When the pH is increased to 7-8 to form the free bases of the nitroacridine chromophores, the 2- and 3-nitro isomers retain the aminoacridine configuration, but the 1- and 4-nitro isomers convert to the iminoacridan configuration. These results are relevant to the ongoing discussion of aminoacridine-iminoacridan tautomerism of these acridine derivatives in solution.

Aminoacridines↗
PubMed1990

Theory Z as a framework for the application of a professional practice model in increasing nursing staff retention on oncology units.

Recruitment and retention of nurses is the most significant issue facing nursing administrators, educators, researchers and clinicians in the ongoing nursing shortage in the United States today. It has been cited in the literature that American nurses feel that job satisfaction is a major issue in retaining qualified nurses in hospitals. Satisfaction occurs when nurse expectations are matched with the hospital's vision and values. It is for this purpose that the authors have chosen theory Z as a hospital management model to coincide with the institution of the Marker Professional Practice Model to increase job satisfaction (autonomy) in hospital-based nurses. There are four 'hidden' challenges in health care today. They are: (a) fundamental changes occurring within the profession and practice of nursing; (b) the expanded role of women in management; (c) ethical dilemmas related to advances in medical technologies; and (d) the difficulty for health care managers in the United States to make changes related to the above three challenges. The authors feel that it is inherent to the nursing profession to combine existing theories and models to enhance the retention of nurses to the profession.

Hospital Units↗
PubMed1989

Cervical spinal deformity following craniotomy and upper cervical laminectomy for posterior fossa tumors in children.

Spinal deformity is not usually regarded as a potential complication of posterior fossa tumor resection. After cervical subluxation had been recognized in 2 children following removal of posterior fossa tumors, a review was carried out to determine the incidence of this complication. Of the 72 children who had undergone resection of a posterior fossa tumor, 4 patients, including the original 2, developed a cervical spinal deformity. Factors that predisposed to this complication included laminectomy of C2 or lower, local wound complications and possibly post-operative neck weakness. It is important to be aware that cervical subluxation can occur after resection of posterior fossa tumors, when laminectomy extending below C1 has been performed. Patients at risk should be followed closely.

Brain Neoplasms↗
PubMed1988

Diffuse well-differentiated lymphocytic lymphoma: chemotherapy with BCNU, cyclophosphamide, vincristine, melphalan and prednisone.

Twenty patients with stage III and IV diffuse well-differentiated lymphocytic lymphoma were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, vincristine, melphalan and prednisone (M-2). Treatment was given every 5 weeks for 11 cycles in responding patients. The median age of the patients was 62 years (range 45-76). There were 12 complete remissions and 6 partial remissions for an overall response rate of 90%. The median duration of remission was 24 months (range 12-79 months) and was identical for complete responders and partial responders. All but 2 responding patients have been subsequently retreated for relapse. The median survival was 84 months (range 1-108 months). Myelosuppression was mild. Nausea/vomiting, neuropathy, alopecia and gastrointestinal symptoms from prednisone were seen in the minority of patients. One patient expired from sepsis/neutropenia during the first cycle of therapy. The M-2 protocol produces effective remissions in diffuse well-differentiated lymphocytic lymphoma. The relapse and survival pattern are similar to the results achieved with other chemotherapy regimens in low-grade lymphoma.

Adult↗
PubMed1987

Microencapsulated tumor assay: new short-term assay for in vivo evaluation of the effects of anticancer drugs on human tumor cell lines.

A new in vivo has been developed for evaluating the antitumor activity of chemotherapeutic drugs. The assay is based on a microencapsulation technology developed by Damon Biotech, Inc., Boston, MA, which makes it possible to encapsulate human tumor cells in small (about 1 mm in diameter) microcapsules with semipermeable membranes. Microcapsules containing human tumor cells were injected i.p. into nude or C57BL/6 mice and drugs were administered i.v. The microcapsules were recovered at various intervals following treatment and determinations of drug effects were made based on the differences in the number of tumor cells recovered from the treated and nontreated animals. Using this assay we found that (a) encapsulated tumor cells grew better in the in vivo system than in vitro under the conditions tested; (b) drugs crossed the capsular membrane and killed or inhibited the proliferation of tumor cells; and (c) the antitumor effect was consistent with the relative therapeutic efficacy of drugs or level of resistance of tumor cells detected by other in vitro or in vivo tests. The tumor microencapsulation assay offers several properties which make it attractive for use in new drug development: (a) the antitumor activity of drugs can be tested against human tumor cells under conditions which provide for three-dimensional growth and in vivo supply of nutrients; (b) the sensitivity of tumor cells can be assessed following exposure to drugs at concentrations which are achievable in vivo; (c) compounds requiring in vivo metabolic activation can be tested; (d) the effect of each drug injection can be quickly evaluated; (e) inhibition of tumor cell proliferation versus cytoreductive effects of drugs can be discriminated; (f) the test is applicable to virtually all histological types of human tumor cells; and (g) the tumor microencapsulation assay is a short-term, simple, and relatively inexpensive assay.

Animals↗