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Biomedical subjects

K Nolan

Publications and source records attributed to K Nolan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Caring for gravely ill children.

BACKGROUND: Much has been written about the care of the hopelessly ill adult, but there is little guidance for pediatric health care professionals in the management of children who are critically or terminally ill. METHODS: Through a 3-day meeting in Tarrytown, NY, attended by a group of pediatricians and others directly involved in these issues, a principled approach was developed for the treatment of, and health care decision-making for, children who are gravely ill. RESULTS: The group agreed that the needs and interests of the child must be the central focus of any treatment plan and that the child should be involved to as great extent possible, consistent with developmental maturity, in the decision-making process. Quality of future life should be viewed as being relevant in all decisions. Parents are believed to be the natural guardians of children and ought to have great latitude in making decisions for them. However, parental discretion is not absolute and professionals must maintain an independent obligation to protect the child's interests. CONCLUSIONS: Decision-making should be collaborative among patient, parents, and professionals. When conflict arises, consultation and ethics committees may assist in resolution. When cure or restoration of function is no longer possible, or reasonable, promotion of comfort becomes the primary goal of management. Optimal use of pain medication and compassionate concern for the physical, psychological, and spiritual well-being of the child and family should be the primary focus of the professionals caring for the dying child.

Adolescent↗
PubMed1994

Azelastine inhibits acute allergic dyspnea in a conscious guinea pig asthma model.

A simple, noninvasive, bias-flow ventilated wholebody plethysmographic technique and noninvasive pulmonary analyzer (Buxco dyspnea monitor) were used to quantitate allergic dyspnea in chronically sensitized freely moving guinea pigs. In this study, the effect of azelastine on aeroallergen-induced dyspnea in allergic guinea pigs was investigated. Aeroallergen challenge produced severe dyspnea which was characterized by a 390% increase in the amplitude of pseudo flow signal, a 93% increase in box pressure (delta P) and a 68% decline in relaxation time; these changes signify a tremendous increase in the effort of breathing. The oral administration of azelastine (1 mg/kg) two hours before aeroallergen provocation significantly inhibited allergic dyspnea in this acute allergic asthma model. This technique permits quantitative measurement of the severity of the airway allergic responses in freely moving guinea pigs.

Aerosols↗
PubMed1993

Aeroallergen-induced dyspnea in freely moving guinea pigs: quantitative measurement by bias flow ventilated whole body plethysmography.

Guinea pigs were sensitized and boostered with i.p. injections of ovalbumin (OA) 10 micrograms + Al(OH)3 100 mg. Thirteen days after the last injection animals (800-1100 g) were placed in bias flow ventilated whole body plethysmographs and allowed to stabilize for 2 h. Lung function was recorded for up to 2 h before and 5 h after aeroallergen challenge (OA 20 mg/ml, 60 s, 20 psi) by a noninvasive pulmonary analyzer for unrestrained rodents. Aeroallergen challenge produced immediate dyspnea and gasping (peaking between 8 and 17 min). Gasping was associated with an increase in amplitude in the box pressure fluctuations (93%), and in the slope of the fluctuations (391%). Respiratory rate increased (103 to 175 breaths/min, 78%), the product of breathing rate times box pressure amplitude increased (161 to 432, 180%). Relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value) declined (0.16 to 0.05 s, 72%). All of these lung dysfunction changes were highly significant (p < 0.001). Lung dysfunction persisted for 60 to 120 min after challenge. One of 8 animals tested died within 10 min. None of the animals exhibited late asthmatic responses during the 5 h post-challenge period. Based on these data we conclude that this technique allows quantitative analysis of dyspnea, gasping, and an abnormal pattern (waveform) of breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pharmacodynamic and pharmacokinetic studies with azelastine in the guinea pig: evidence for preferential distribution into the lung.

The correlation between the antiasthma activity of azelastine and the concentrations of azelastine and its major metabolite, desmethylazelastine, in the blood and lung were investigated in guinea pigs. Blood and lung tissue samples collected at 15 min after aeroallergen (ovalbumin, 0.5 mg/ml, 30 s, 15 psi) challenge, i.e., 2-1/4 h after oral administration of the drug, were analyzed for azelastine and its desmethyl metabolite by specific HPLC assay. Azelastine afforded protection against immediate allergic responses (IAR, characterized by gasping and bronchospasmic convulsions). Based on the reduction of the severity of IAR, the ID50 was 0.04 mg/kg. It also delayed the onset of IAR and prevented mortalities. A positive correlation (r2 = 0.944) between the antiallergic activity and the sum concentrations of azelastine and desmethylazelastine in the lung was observed. Preferential uptake of azelastine and desmethylazelastine by the lung was demonstrated by the mean lung/blood ratio of about 22 and 146, respectively. The selective uptake of azelastine and its active metabolite by the lungs could contribute to its antiasthmatic/antiallergic activity in guinea pigs.

Animals↗
PubMed1993

Decisions near the end of life: professional views on life-sustaining treatments.

OBJECTIVES: How do health care professionals assess the care of hospital patients near the end of life? Are physicians and nurses aware of and in agreement with national recommendations regarding patients' rights to forgo life-sustaining medical treatments and to receive adequate pain control? METHODS: We surveyed 687 physicians and 759 nurses in 5 hospitals. RESULTS: Almost half (47%) of all respondents and fully 70% of the house officers reported that they had acted against their conscience in providing care to the terminally ill. Four times as many respondents were concerned about the provision of overly burdensome treatment than about undertreatment. CONCLUSIONS: In summary, many physicians and nurses were disturbed by the degree to which technological solutions influence care during the final days of a terminal illness and by the undertreatment of pain. However, changes in the care of dying patients may not have kept pace with national recommendations, in part because many physicians and nurses disagreed with and may have been unaware of some key guidelines, such as the permissibility of withdrawing treatments.

Attitude of Health Personnel↗
PubMed1992

Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach.

In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependent fashion. The resulting ED50 was 10 (3.4-32.8) micrograms/kg. The clinical therapeutic usefulness of anti-IL-5 or anti-IL-5-producing cells in asthma/allergy treatment remains to be an intriguing possibility.

Animals↗
PubMed1992

Repeated aeroallergen challenge induces lung dysfunction but not bronchial hyperresponsiveness in conscious guinea pigs.

Adult male Hartley-strain guinea pigs were sensitized by 10 min exposure to aerosolized 1% ovalbumin (OA; 10 mg/ml in normal saline containing 4% heat-killed B. pertussis vaccine and 0.02% antifoam B emulsion). One week after sensitization, animals were placed in an exposure chamber and challenged (nebulized OA 0.5%) until each animal showed labored breathing. Maximal exposure time was 10 min. Diphenhydramine (20 mg/kg, i.p.) was given 1 h before each OA challenge to protect the animals from bronchospasmic death. Antigen challenge was repeated twice a week for 2 weeks. The specific airway resistance (sR(aw)) changes in response to increasing concentrations of aerosolized acetylcholine (Ach) were determined. The data obtained in this study demonstrated that repeated antigen challenge produced a significant bronchial tone i.e. an increase in sR(aw) and a decline in specific airway conductance (sG(aw)) and failed to induce bronchial hyperreactivity to aerosolized acetylcholine (Ach) in conscious guinea pigs.

Acetylcholine↗
PubMed1992

Characterization of aeroallergen-induced dyspnea in unrestrained guinea pigs by bias-flow-ventilated whole body plethysmography.

Aeroallergen-induced dyspnea in guinea pigs was associated with an increase in amplitude in the box pressure fluctuations (212%) and pseudo-flow signal (604%) and an 80% decline (from 0.19 to 0.04 s) in relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value). All of these lung dysfunction changes were highly significant (P < 0.001). Pyrilamine (1 mg/kg, p.o., -2 h) inhibited dyspnea (delta P and delta F) by 50-53%. This technique allows quantitative analysis of allergic dyspnea in conscious, unrestrained guinea pigs.

Aerosols↗
PubMed1992

Inhibition of aeroallergen-induced bronchial eosinophilia by azelastine in guinea pigs.

The ability of azelastine to influence allergic bronchial eosinophil infiltration in guinea pigs was studied. Aeroallergen challenge of actively sensitized guinea pigs produces eosinophil infiltration in bronchoalveolar lavage fluid collected 20-24 h after aeroallergen exposure. Azelastine and methylprednisolone, administered orally 2 h before challenge, inhibited eosinophilic infiltration yielding the ED50s of 1.55 and 4.48 mg/kg, respectively. WEB-2086, a platelet-activating factor antagonist (3 mg/kg), and theophylline, a phosphodiesterase inhibitor (30 mg/kg), also suppressed allergic bronchial infiltration of eosinophils by 44%. The data obtained in this study demonstrate that azelastine exerts direct bronchial anti-inflammatory activity in guinea pigs.

Administration, Oral↗
PubMed1991

Commentary: how do we think about the ethics of human germ-line genetic therapy?

The line between germ-line genetic therapy and somatic cell is more and more difficult to discern. With new abilities to effect germ-line genetic therapy it is less clear why such therapy should not be undertaken. Nonetheless, questions persist as to who is the patient in such therapy and about the extent of discretion that should be allowed prospective parents and the physician/researcher.

Ethics, Medical↗
PubMed1991

A comparison of the caffeine halothane muscle contracture test with the molecular genetic diagnosis of malignant hyperthermia.

Malignant hyperthermia (MH) is currently diagnosed by the caffeine-halothane contracture (CHC) test. In a previous study, this test was used to establish linkage between the human gene for MH susceptibility and the ryanodine receptor (RYR) gene. The current study extends the genetic linkage analysis to a large French-Canadian kindred. In this family, genetic linkage between RYR and MH genes was not demonstrable using the currently recommended limits of normal for the CHC test in the identification of MH-susceptible individuals. With CHC test threshold limits below those currently recommended, however, complete linkage between the RYR and MH genes was seen. Comparisons of CHC test results with genetic linkage studies will increase the diagnostic accuracy of both tests as well as generate new insights into the biology of MH.

Alleles↗
PubMed1991

Toward an expanded vision of clinical ethics education: from the individual to the institution.

This paper advances a new paradigm in clinical ethics education that not only emphasizes development of individual clinicians' skills, but also focuses on the institutional context within which health care professionals work. This approach has been applied to the goal of improving the care provided to critically and terminally ill adults. The model has been adopted by about thirty hospitals and nursing homes; additional institutions will soon join the program, entitled Decisions Near the End of Life. Here, we describe the history and rationale for this approach, its goals, pedagogical assumptions, and design.

Curriculum↗
PubMed1990

Aeroallergen-induced immediate asthmatic responses and late-phase associated pulmonary eosinophilia in the guinea pig: effect of methylprednisolone and mepyramine.

Guinea pigs were sensitized by intraperitoneal injection of ovalbumin, 10 micrograms mixed with 100 mg A1(OH)3 in saline. On days 15-30 sensitized guinea pigs were challenged with ovalbumin aerosol (0.5 mg/ml, 30 s, 15 psi) which produced immediate asthmatic responses characterized by dyspnea, convulsions, and some deaths during the first 14 min. Twenty to 24 h later the animals were sacrificed with an overdose of pentobarbital, and lungs, bronchi, and lower trachea were dissected and fixed in 10% neutral buffered formalin. Histopathological examination of randomly coded tissues of the respiratory tract revealed a pulmonary eosinophilic cellular infiltrate in the epithelium/subepithelium of trachea, bronchi, and bronchioles as well as the peribronchial, peribronchiolar, and perivascular areas of the lungs. Oral administration of mepyramine (10 mg/kg) 2 h before aeroallergen challenge provided complete protection against immediate asthmatic responses and prevented deaths during the first 14 min without influencing the late phase associated lung eosinophilic cellular infiltrate. The immediate asthmatic responses were not influenced by methylprednisolone (30 mg/kg) administered orally 24 and 2 h before aeroallergen challenge. Following an additional dose of methylprednisolone 4 h after challenge, there was a significant inhibition of pulmonary eosinophilia (30 mg/kg; -24 h, -2 h, and +4 h). These observations suggest that histamine is the principal mediator of immediate asthma attacks in guinea pigs. Methylprednisolone may be acting by inhibiting the production of eosinophil chemotactic factor of anaphylaxis (platelet-activating factor or leukotriene B4) from the alveolar macrophages, T lymphocytes, and perhaps other cells, thus preventing pulmonary eosinophilia.

Administration, Oral↗
PubMed1990

Inhibition of 5-HETE, LTB4, and LTC4 formation by azelastine in rat mixed peritoneal cells.

Azelastine produced a concentration-dependent inhibition of calcium ionophore A23187 (0.2 microM) stimulated generation of 5-HETE, leukotriene B4, and leukotriene C4 in rat mixed peritoneal cells, yielding IC50 values of 35.5, 47.4, and 31.7 microM, respectively. Nordihydroguaiaretic acid (a potent 5-lipoxygenase inhibitor) also exerted a strong and concentration-dependent inhibition of 5-HETE and leukotriene B4 and C4 formation with IC50 values of 0.15, 0.09, and 0.1 microM, respectively. The inhibition of the formation of the products of the lipoxygenase pathway of arachidonic acid metabolism by azelastine may contribute to its overall antiallergic, antiasthmatic, and pulmonary anti-inflammatory activities.

Animals↗
PubMed1990

Inhibition of PAF-induced histamine secretion and bronchoconstriction by WEB 2086.

Platelet activating factor (PAF) stimulates histamine secretion from rabbit mixed leukocytes in a concentration-dependent fashion (EC50 10 ng/ml). The PAF (10 ng/ml)-induced histamine secretion was inhibited by WEB 2086 (IC50 = 20 nM). Furthermore, PAF (10 ng/kg, i.v.)-induced bronchoconstriction in guinea pig was also inhibited by WEB 2086 (ID50 = 5.3 micrograms/kg, i.v., 5 minutes). These data showed the existence of PAF-receptors on rabbit basophils and in guinea pig airways which are highly sensitive to blockade by WEB 2086.

Animals↗
PubMed1990

Changes in aeroallergen-induced pulmonary mechanics in actively sensitized guinea pig: inhibition by azelastine.

The influence of orally administered azelastine and selected H1-receptor antagonists on aeroallergen-induced acute lung anaphylactic responses in actively sensitized guinea pigs (experimental asthma model) was studied. Azelastine (1 mg/kg, PO, two hours) exerted significant inhibition of the aeroallergen-induced decline in dynamic lung compliance and an elevation in pulmonary airway resistance. Terfenadine, pyrilamine, and diphenhydramine given as oral doses of 1 mg/kg two hours before aeroallergen challenge exerted weak or no inhibition of acute lung anaphylactic responses. In conclusion, the data obtained in this study showed that azelastine administered orally is capable of exerting antiasthmatic effects in both the central and peripheral airways of guinea pigs. This effect may be attributed to its ability to inhibit the formation or secretion of pharmacologic mediators (ie, histamine, LTC4/D4, .O2-) from inflammatory cells.

Air Pollution↗