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Biomedical subjects

K Nolan

Publications and source records attributed to K Nolan.

At least 19 recordsLinked to original sources
PubMed1998

Rpb3, stoichiometry and sequence determinants of the assembly into yeast RNA polymerase II in vivo.

Stoichiometry of the third largest subunit (Rpb3) of the yeast RNA polymerase II is a subject of continuing controversy. In this work we utilized immunoaffinity and nickel-chelate chromatographic techniques to isolate the RNA polymerase II species assembled in vivo in the presence of the His6-tagged and untagged Rpb3. The distribution pattern of tagged and untagged subunits among the RNA polymerase II molecules is consistent with a stoichiometry of 1 Rpb3 polypeptide per molecule of RNA polymerase. Deletion of either alpha-homology region (amino acids 29-55 or 226-267) from the Rpb3 sequence abolished its ability to assemble into RNA polymerase II in vivo.

Amino Acid Sequence↗
PubMed1998

Pragmatic science: accelerating the improvement of critical care.

Adapting practices that are described in the literature or used effectively in other critical care units provides an opportunity to improve the quality of critical care and reduce costs. Described in the literature are different techniques for the gradual withdrawal of mechanical ventilator support from patients during weaning from the ventilator. Phoebe Putney Memorial Hospital in Albany, GA used a systematic approach to adapt these techniques to improve the weaning process. This resulted in a reduction in the number of days patients were on a ventilator and a reduction in the ICU length of stay for patients with acute respiratory failure requiring mechanical ventilation.

Clinical Protocols↗
PubMed1997

Measuring the quality of health care: state of the art.

BACKGROUND: September 12-13, 1996, in Washington, DC, the Institute of Medicine, as part of its Special Initiative on Health Care Quality, held an invitational conference to illustrate exemplary quality measurement and to discuss the results. Patient reports, innovative uses of outcome measures for quality improvement, risk adjustment, assessment in integrated health plans and health care settings, clinical guidelines, and projects on disseminating information on quality measurement techniques and tools were among the topics represented. IMPROVING MEDICATION USE: Brent James described studies undertaken to reduce adverse drug events (ADEs). When implementing any measurement system where error is a possible factor, it is important to emphasize identifying problems for the purpose of learning, not judgment. Lucian Leape agreed that staff involved must feel that the purpose of the study is to examine system problems, not individuals' mistakes. David Classen described a nonproprietary computerized disease-management program designed to reduce ADEs in infectious diseases. "A QUALITY VISION": Robert Brook said that the relationship between cost or resources devoted to care and quality is not well understood and is certainly not simple. He also said that although investments in measurement strategies are needed to make them better, that doesn't mean we shouldn't attempt to use the measurements we have now. CLOSING ADDRESS: Mark Chassin said that the presentations at the conference provided evidence that should allow us to conclude beyond a reasonable doubt that quality can be measured-with a degree of scientific precision equal to that of most of the measures used to take care of patients every day.

Health Services Research↗
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↗