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Biomedical subjects

M Kelley

Publications and source records attributed to M Kelley.

142 records · Page 8Linked to original sources

Fluroxene mutagenicity.

The commercially available volatile anesthetic fluroxene (2,2,2-trifluoroethyl vinyl ether) which contains the stabilizer N-phenyl-1-napthylamine, was tested for mutagenicity using four strains of S. typhimurium, TA1535, TA1537, TA98 and TA100, and one strain of E. coli, WP2. In addition, purified fluroxene; N-phenyl-1-napthylamine; trifluoroethanol, a major metabolite of fluoroxene; and urine from rats anesthetized with fluroxene were tested. Several procedures were utilized including exposure of bacteria to vapor in desiccators and in liquid suspension. Results indicate that fluroxene, but not its stabilizer, was mutagenic to strains TA1535, TA100 and WP2 only in liquid suspension and only in the presence of a rat-liver enzyme system. Trifluoroethanol and urine from fluroxene-treated rat were not mutagenic to any strain of bacteria. These findings indicate that fluroxene is a promutagen which requires preincubation before it is recognized. Further experiments were performed with enzymes prepared from mouse, hamster and human liver. Fluroxene was mutagenic only in the presence of enzymes prepared from Aroclor 1254 pretreated rodents. Since fluroxene was not mutagenic in the presence of enzymes prepared from three human livers, the significance of these findings to man are unclear.

Animals↗

Mutagenicity of halogenated ether anesthetics.

An in vitro microbial assay system employing two histidine-dependent strains of Salmonella typhimurium, TA1535 and TA100, was used to test the mutagenicities of enflurane, methoxyflurane, isoflurane and fluroxene. Enflurane, isoflurane and fluroxene in concentrations ranging from 0.01 to 30 per cent and methoxyflurane in concentrations ranging from 0.01 to 7 per cent were incubated with bacteria in the presence or absence of homogenates of liver prepared from rats pretreated with the enzyme inducer, Aroclor 1254. Enflurane, methoxyflurane, isoflurane, and urines from patients anesthetized with these agents were not mutagenic. Fluroxene, however, was highly mutagenic, and therefore poses a possible hazard for operating room personnel and patients.

Anesthesia, Inhalation↗

Acute sedative properties of SKF 525A in rats: implications for its use as a metabolism inhibitor in the study of psychoactive drugs.

SKF 525A was found possess sedative properties in rats at doses of 25 and 50 mg per kg, when injected intraperitoneally. The behavioural effects of the drug were assessed in two ways. Firstly, by "Time Sampling Behavioural Categorisation" of explatory behaviour; and secondly by activity measurements obtained with an ultrasonic motion recorder. The results clearly demonstrate that SKF 525A has sedative properties in rats at doses which are conventionally used to inhibit metabolism of a wide range of drugs. The implications of these results for the use of SKF 5251 in the study of the actions of psychotropic drugs are discussed.

Animals↗

Telephone triage in the office setting.

During a six-month period in 1988, two nurse-midwives documented the telephone calls they received in an OB/GYN/CNM practice. Calls were then tallied and categorized for analysis. A discussion of the numbers and types of calls is presented as well as a review of the literature on telephone triage/management.

Emergency Medical Services↗

Synthesis and molecular characterization of a biotinylated analog of [Lys]bradykinin.

We report the synthesis and molecular characterization of a biotinylated analog of kallidin, [Lys]bradykinin. Bradykinin was prepared by solid phase peptide synthesis. Before cleavage from the resin, a biotin moiety was coupled to the epsilon amino group of a lysine in the zeroth position of the bradykinin peptide. An omega-amino caproic acid spacer was incorporated between the biotin group and the N-terminal lysine. The biotinylated peptide was deprotected, cleaved from the resin and purified by RP-HPLC. The identity of this analog was confirmed by amino acid analysis and FAB-mass spectrometry. Biotinyl [Lys]bradykinin (BLBK, mol, wt. = 1528) inhibited [3H]-bradykinin binding to guinea pig ileum homogenates dose dependently, with an IC50 of 28.9 +/- 6 nM. The IC50 for [Lys]bradykinin was approximately 10-fold lower, 3.2 +/- 0.6 nM. BLBK induced contractility in an isolated guinea pig smooth muscle preparation with an EC50 of 129 +/- 14 nM; the corresponding value for [Lys]bradykinin was 29 +/- 8 nM. These data are consistent with the difference in binding potency observed for BLBK compared to [Lys]bradykinin. In an ELISA assay using BLBK and affinity-purified rabbit anti-bradykinin antibody, BLBK bound to anti-bradykinin antibody with an EC50 = 1.21 +/- 0.54 nM. Rank order potencies for several bradykinin peptide analogs suggest that the epitope on bradykinin recognized by the antibody is likely to be at the carboxy terminus of the peptide.

Amino Acid Sequence↗

Dopamine and norepinephrine activity in schizophrenia. An integrative perspective.

The dopamine (DA) hypothesis of schizophrenia stated that increased DA activity is the primary cause of schizophrenia. Recently, even though increased DA activity is in fact involved in psychotic symptoms and antipsychotic drug response, it has become clear that decreased DA activity is present in remitted and chronic states and may relate to deficit symptoms and cortical lesions. In addition, the norepinephrine (NE) system seems to be involved in symptomatology, antipsychotic drug response, course, and outcome in schizophrenia. This review supports the hypothesis that a disturbance in DA and NE activity regulates schizophrenic behavior. A plethora of DA- and NE-related findings in schizophrenic patients are reviewed in relationship to each other according to basic science data and to presently entertained hypotheses, with emphasis on a neural developmental disturbance interacting with a genetic predisposition shaped by environmental factors.

Brain↗

Treatment as harm reduction, defunding as harm maximization: the case of methadone maintenance.

Despite numerous research studies demonstrating the efficacy of methadone maintenance treatment (MMT) in general and the value of retention in particular, the increasing defunding of this modality has compromised its potential. From 1990 to 1995 the lead author conducted a longitudinal research project to determine the impact of the cost of treatment on 233 San Francisco Bay Area study participants seeking, enrolled in, or defunded from MMT. This paper reports on selected findings from that study. Using variables of drug use, crime, gender and HIV risk, qualitative and quantitative results comparing those seeking treatment with those enrolled in treatment indicated that MMT functioned as a harm-reduction tool. When clients were defunded, however, drug use, crime and HIV risk increased and harm was maximized.

HIV Infections↗

How close is North Carolina to meeting Medicare's clinical priorities?

The analyses upon which this publication is based were performed under Contract No. 500-99-NC03, entitled "Utilization and Quality Control Peer Review Organization for the State of North Carolina," sponsored by the Health Care Financing Administration, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by the Health Care Financing Administration, which has encouraged identification of quality improvement projects derived from analysis of patterns of care, and therefore required no special funding on the part of this contractor. Ideas and contributions to the author concerning experience in engaging with issues presented are welcomed.

Centers for Medicare and Medicaid Services, U.S.↗

When the rehabilitation ideal fails: a study of parental rights termination.

This study explored the circumstances of parents whose extreme neglect and abuse of their young children justified the drastic state action of termination of their parental rights. Records of 97 children age 6 and under whose parental rights were terminated between 1991 and 1997 in Minnesota were reviewed. Profiles of parents and children were drawn from these data, and a "risk pool" of parents whose children became wards of the state was identified. Guidelines are drawn from this "risk pool" that may help alert practitioners to those parents who are unlikely to safely maintain their children. Questions and implications for policy and practice are highlighted.

Adolescent↗