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Biomedical subjects

M M Morris

Publications and source records attributed to M M Morris.

54 records · Page 3Linked to original sources

Anticholinergics and human brain stem auditory evoked potentials.

The effect of premedication with morphine and anticholinergic drugs on absolute and interpeak latencies of brain stem auditory evoked potentials was studied in thirty patients. Two commonly used anticholinergics, glycopyrrolate and scopolamine, given in combination with morphine were studied. Patients premedicated with morphine alone served as a control group. No significant change in either absolute or interpeak latencies was noted in patients premedicated with either morphine alone or morphine and glycopyrrolate. Results in patients premedicated with morphine and scopolamine are inconclusive because of large intersubject variability.

Adolescent↗

Asymptomatic bronchial hyperresponsiveness in rhinitis.

Methacholine inhalation tests are used to help in the diagnosis of asthma when spirometry is normal. However, the significance of increased methacholine responsiveness in patients with rhinitis and no symptoms of asthma is not known. One possibility is that it is a false positive result; another possibility is that it indicates subclinical asthma. We investigated these possibilities in 25 patients with rhinitis, whose attending physician had not made a diagnosis of asthma, by comparing responsiveness to methacholine expressed as the provocation concentration to cause a fall in FEV1 of 20% (PC20) with responsiveness to the natural stimulus of isocapnic hyperventilation of cold air and the diurnal variation of peak flow rate. Asthma was recognized objectively by variable airflow obstruction documented by one of the latter two tests. The PC20 ranged between 4 and greater than 64 mg/ml. In 10 patients the PC20 was less than 16 mg/ml. Five of these patients had bronchoconstriction in response to hyperventilation, and a further two patients demonstrated increased variability of peak flow rates. Thus, in seven of 10 patients, increased bronchial responsiveness was confirmed by the use of two different methods, although they were asymptomatic, and the increased response to methacholine was not a false positive result. In the remaining three patients the PC20 was borderline increased (8 to 16 mg/ml). The results indicate that methacholine responsiveness in the asthmatic range in patients with rhinitis is associated with variable airflow obstruction and subclinical asthma.

Adolescent↗

The effect of inhaled hexamethonium bromide and atropine sulphate on airway responsiveness to histamine.

The degree of protection against inhaled histamine achieved by inhalation of the ganglion blocker hexamethonium bromide plus placebo, hexamethonium plus atropine sulphate, and placebo plus placebo was examined in six atopic subjects, four of whom had current asthma. Hexamethonium was administered until there was systemic evidence of ganglionic blockade with a postural drop in blood pressure of 31 +/- 7.5 mm Hg (mean +/- SD) (p = 0.01) and an increase in heart rate of 30 +/- 3.1 bpm (mean +/- SD) (p = 0.01). Atropine was inhaled in a dose (18 mg nebulized during tidal breathing) known to produce systemic inhibition of cardiac and salivary cholinergic (muscarinic) receptors. The airway effects were measured by FEV1. Hexamethonium caused bronchoconstriction in all four subjects with asthma, which was reversed by atropine. The mean provocation concentration of histamine to provoke a 20% fall in FEV1 was 2.97 mg/ml after premedication with placebo, it was not different at 2.84 mg/ml after hexamethonium alone, and it increased slightly to 5.31 mg/ml after both hexamethonium and atropine (p = 0.06). The results suggest that the main effect of inhaled histamine is not by reflex bronchoconstriction but rather through stimulation of H1-receptors on airway smooth muscle. Therefore, histamine hyperresponsiveness in asthma is not primarily caused by a defect in the parasympathetic nervous supply to the airway.

Adult↗

Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis.

In a previous study on 27 patients with chronic bronchitis we found that only three developed bronchoconstriction in response to hyperventilation of cold, dry air despite an increased responsiveness to methacholine inhalation. We therefore investigated bronchial responsiveness to hyperventilation with cold, dry air and methacholine in 27 patients with stable asthma who had a similar range of baseline FEV1 values but who developed bronchoconstriction that could be reversed to give an FEV1 more than 70% of the predicted value. Baseline FEV1 was 0.88-3.98 l (37-114% predicted). All but one subject developed bronchoconstriction in response to hyperventilation. There was a linear relationship between baseline FEV1 and response to methacholine (r2 = 0.37, p less than 0.001) and the relationship was significantly different from that found in the bronchitic subjects (F2.50 = 24.94, p less than 0.001). In general, the response to methacholine was greater in the asthmatic than in the bronchitic subjects for any baseline FEV1. The results suggest that there are different mechanisms underlying the increased responsiveness to methacholine in asthma and chronic bronchitis.

Adolescent↗

Bronchial responsiveness to methacholine in chronic bronchitis: relationship to airflow obstruction and cold air responsiveness.

The response to inhaled methacholine is increased in patients with chronic airflow obstruction, but it is not known whether this is due to true hyperresponsiveness or is a result of the airflow obstruction. In asthmatics the response to methacholine correlates with the bronchoconstriction produced by hyperventilation of cold dry air. We studied 27 patients with a history of smoking and chronic bronchitis with a range of severity of airflow obstruction. Bronchial responses to methacholine (expressed as the provocation concentration causing a fall in FEV1 of 20%-PC20) and isocapnic hyperventilation of cold dry air were measured. In 19 patients the PC20 was less than 8 mg/ml (that is, in the asthmatic range) but only three developed bronchoconstriction in response to hyperventilation. There was a linear correlation between the log PC20 and the FEV1 (r = 0.86, p less than 0.001). The results suggest that in patients with chronic airflow obstruction the response to methacholine is determined by the degree of airflow obstruction, and cannot be used in the diagnosis of asthma in the absence of additional information.

Adult↗

Inhibition by sodium cromoglycate of bronchoconstriction stimulated by respiratory heat loss: comparison of pressurised aerosol and powder.

The protective effect was examined of three doses (2, 10, and 20 mg) of sodium cromoglycate inhaled from a pressurised metered dose inhaler on the response to isocapnic hyperventilation of cold dry air in 10 asthmatic subjects. This was compared with the effect of cromoglycate powder (20 mg) inhaled from a Spincap and with placebo given on two occasions. The medications were inhaled on separate days, in random order and with the use of a double blind double dummy technique, 20 minutes before isocapnic hyperventilation of two fold increasing volumes of air (-15 degrees C, 0% humidity) to produce a 20% fall in the post-treatment FEV1. The response was expressed as the provocative dose of respiratory heat loss required to cause a fall in FEV1 of 15% (PD15, kcal/min). The mean baseline spirometric indices exceeded 85% of predicted normal values on each test day; both placebo treatments reduced the baseline FEV1 by comparison with all active treatments (p less than 0.0001). Comparison of the PD15 on the two placebo days confirmed excellent reproducibility. All doses of cromoglycate shifted the respiratory heat loss dose-response curve to the right of the placebo curve; PD15 after all active treatments exceeded PD15 after placebo (p less than 0.0001). There was no cromoglycate dose-response relationship between the three doses of aerosol (p greater than 0.05), or between any dose of aerosol and powder (p greater than 0.05). It is concluded that cromoglycate aerosol inhaled from a pressurised inhaler in a dose of 2 mg gives the same magnitude of protection against bronchoconstriction stimulated by airway cooling as 20 mg of pressurised aerosol or powder from a Spincap.

Adult↗

Nursing educators: perceptions of the curricular role of human genetics/bioethics.

In recent years medical geneticists have made tremendous advances in understanding hereditary diseases. Applying this new knowledge raises serious ethical questions which have relevance to nursing practice. Nursing educators must ask themselves: (1) what effects do these advances have on nursing practice; (2) have the subjects of human genetics and bioethics been sufficiently integrated into nursing educational programs; and (3) are professional nurses prepared to help patients become scientifically literate relative to principles of human genetics? A 35-item questionnaire was prepared, and 616 copies were mailed to the chief administrators of 31 Indiana state-approved nursing programs listed by the Indiana State Board of Nurses' Registration and Nursing Education. Data obtained from the 250 questionnaire respondents led to the conclusion that Indiana nursing educators are aware of the relevance of human genetics to their work, but they need direct access to helpful information to incorporate genetics instruction as a part of nursing education programs in Indiana. To accomplish this task, the respondents favor continuing education programs in human genetics. Although the data are based on responses of Indiana nursing educators, we believe that our findings can be generalized, at least, to nursing programs throughout the midwest. On the basis of our study, we recommend that continuing education programs in human genetics be implemented with the goal of providing all practicing nurses with a better understanding of the genetic basis of disease, thereby enabling them to counsel wisely those patients entrusted to their care.

Bioethics↗

Bronchoconstriction stimulated by airway cooling. Better protection with combined inhalation of terbutaline sulphate and cromolyn sodium than with either alone.

We compared the effect of inhaled terbutaline sulphate (1,000 micrograms), cromolyn sodium (20 mg), terbutaline plus cromolyn, and placebo on the response to respiratory heat loss (RHL) in 10 asthmatics in whom terbutaline alone did not completely inhibit the response to RHL. The medications were taken double-blind in random order 20 min before voluntary isocapnic hyperventilation of subfreezing air (-14 degrees C, 0% humidity) in twofold-increasing amounts. The response was expressed as the provocative dose of RHL to cause a 10 and 20% fall in forced expiratory volume in one second (FEV1). When compared with placebo, terbutaline produced bronchodilation and inhibition of the response to RHL. The degree of bronchodilation was small (mean delta FEV1, 3.9%) and did not correlate with the degree of protection. Cromolyn produced no bronchodilation and similar inhibition. The effect of terbutaline and cromolyn together was additive. We conclude that when bronchoconstriction stimulated by airway cooling is not prevented by a beta agonist or cromolyn given individually, that it will be more effectively inhibited by the 2 drugs given in combination.

Adult↗

Mutagens from the cooking of food. II. Survey by Ames/Salmonella test of mutagen formation in the major protein-rich foods of the American diet.

The formation of mutagens in the major cooked protein-rich foods in the US diet was studied in the Ames Salmonella typhimurium test. The nine protein-rich foods most commonly eaten in the USA--ground beef, beef steak, eggs, pork chops, fried chicken, pot-roasted beef, ham, roast beef and bacon--were examined for their mutagenicity towards S. typhimurium TA1538 after normal 'household' cooking (deep frying, griddle/pan frying, baking/roasting, broiling, stewing, braising or boiling of 100-475 degrees C). Well-done fried ground beef, beef steak, ham pork chops and bacon showed significant mutagen formation. For chicken and beef steak high-temperature broiling produced the most mutagenicity, followed by baking/roasting and frying. Stewing, braising and deep frying produced little mutagen. Eggs and egg products produced mutagens only after cooking at high temperatures (the yolk to a greater extent than the white). Commercially cooked hamburgers showed a wide range of mutagenic activity. We conclude that mutagen formation following cooking of protein-containing foods is a complex function of food type, cooking time and cooking temperature. It seems clear that all the major protein-rich foods if cooked to a well-done state on the griddle (eggs only at temperatures above 225 degrees C) or by broiling will contain mutagens detectable by the Ames/Salmonella assay. This survey is a step towards determining whether any human health hazard results from cooking protein-rich foods. Further testing in both short- and long-term genotoxicity bioassays and carcinogenesis assays are needed before any human risk extrapolations can be made.

Animals↗

Mutagens from the cooking of food. III. Survey by Ames/Salmonella test of mutagen formation in secondary sources of cooked dietary protein.

A survey of mutagen formation during the cooking of a variety of protein-rich foods that are minor sources of protein intake in the American diet is reported (see Bjeldanes, Morris, Felton et al. (1982) for survey of major protein foods). Milk, cheese, tofu and organ meats showed negligible mutagen formation except following high-temperature cooking for long periods of time. Even under the most extreme conditions, tofu, cheese and milk exhibited fewer than 500 Ames/Salmonella typhimurium revertants/100 g equivalents (wet weight of uncooked food), and organ meats only double that amount. Beans showed low mutagen formation after boiling and boiling followed by frying (with and without oil). Only boiling of beans followed by baking for 1 hr gave appreciable mutagenicity (3650 revertants/100g equivalents). Seafood samples gave a variety of results: red snapper, salmon, trout, halibut and rock cod all gave more than 1000 revertants/100 g wet weight equivalents when pan-fried or griddle-fried for about 6 min/side. Baked or poached rock and deep-fried shrimp showed no significant mutagen formation. Broiled lamb chops showed mutagen formation similar to that in red meats tested in the preceding paper: 16,000 revertants/100 g equivalents. These findings show that as measured by bioassay in S. typhimurium, most of the foods that are minor sources of protein in the American diet are also minor sources of cooking-induced mutagens.

Animals↗

Metabolism of limonene-1,2-epoxide in the rat.

1. The metabolism of limonene-1,2-epoxide was studied following intraperitoneal injection in rats and in rat liver homogenates. 2. Limonene-1,2-glycol was the only neutral metabolite detected. Major limonene metabolites, p-mentha-2,8-dien-1-alpha and -beta-ol and p-mentha-1,8-dien-6-alpha and -beta-ol were not observed. 3. Limonene-1,2-epoxide is not a major intermediate in limonene metabolism in the rat.

Animals↗

Gastric shake test and pharyngeal lecithin/sphingomyelin ratios in new born infants.

Gastric shake test and pharyngeal lecithin/sphingomyelin ratios were measured in newborn infants with respiratory difficulties, and in low birth weight infants in the immediate neonatal period. Both tests were useful in distinguishing infants with idioathic respiratory distress syndrome from those with respiratory difficulty due to other causes. However, in six infants with idiopathic respiratory distress syndrome, the pharyngeal lecithin/sphingomyelin ratio indicated mature lungs, and in three of these, the gastric shake test showed the presence of surfactant. Five of these six infants had been delivered by emergency lower segment caesarean section because of maternal complications, which might account for the discrepancy between the laboratory results and the clinical condition of the patient.

Cesarean Section↗

Protective effects of fluticasone on allergen-induced airway responses and sputum inflammatory markers.

BACKGROUND: A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made. OBJECTIVE: To compare the effects of pretreatment with fluticasone 250 microg 30 min before allergen inhalation and two weeks of 250 microg twice daily (last dose 24 h before challenge) with single and regular (twice daily) placebo doses on early and late asthmatic responses, induced sputum cell counts and measures of eosinophil activation at 7 h and 24 h, and methacholine airway responsiveness at 24 h. PATIENTS AND METHODS: Ten mild asthmatic patients were studied in a randomized, double-blind, placebo controlled crossover study. RESULTS: Regular fluticasone increased the baseline mean provocative concentration of methacholine to cause a 20% fall (PC20) in forced expiratory volume in 1 s (FEV1) from 2.6 to 6.4 mg/mL (P<0.05) and lowered the eosinophil count from 3.1% to 0.4% (P<0.05) compared with regular placebo. Neither single nor regular fluticasone had any effect on the early asthmatic response. Single fluticasone attenuated the late asthmatic response, the mean +/- SEM maximum percentage fall in FEV1 (10.8+/-3.6 compared with single placebo 18. 8+/-3.5, P=0.03), the allergen-induced increase of airway responsiveness (P<0.05), and the eosinophilia (P<0.005) and activated eosinophils at 7 h (P<0.01) but not at 24 h. Regular fluticasone also attenuated the late asthmatic response (11.1+/-2.5) compared with regular placebo (19.6+/-4.5), but this was not statistically significant and did not protect against the induced increase in airway responsiveness or the sputum eosinophilia. CONCLUSION: Two weeks of regular inhaled fluticasone discontinued 24 h before allergen challenge does not offer any additional protection against the early or late asthmatic responses, increased airway responsiveness or sputum eosinophilia compared with a single dose of 250 microg immediately before allergen challenge, despite increasing baseline PC20 and decreasing sputum eosinophilia prechallenge. The significance of the protective effect of a single dose of inhaled steroid before an allergen inhalation and the duration of the protective effect need further investigation.

Administration, Topical↗

A sialoglycoprotein (LEA.135) associated with favourable prognosis of patients with lymph node-negative primary breast carcinoma.

A cell-surface sialoglycoprotein (LEA.135) was identified using a monoclonal antibody that was generated by immunization of Balb/c mice with extracts of normal breast tissue following prior immune-tolerization with mammary carcinoma cell lines. LEA.135 is distinct from other known epithelial cell-associated antigens, including the family of mucins or keratins and epidermal growth factor receptor. Using immunohistochemical staining methods, LEA.135 expression was detected predominantly on the apical plasma membrane of normal and neoplastic mammary and extramammary epithelial cells in freshly frozen or formalin-fixed paraffin-embedded tissue sections. A retrospective study of 111 cases of lymph node-negative patients (TanyN0M0) with primary infiltrating ductal breast carcinoma, with a median follow-up of 7.9 years, was conducted. A comparison of overall survival (O.S.) was made of patients whose tumor cells exhibited reactivity with anti-LEA.135 antibody (O.S. 92.9 +/- 3.3% at 8 years), compared with those whose specimens showed the absence of LEA.135 expression (O.S. 68.3 +/- 10.8% at 8 years). A statistically significant univariant association between LEA.135 expression and O.S. was observed (logrank p < 0.001). In addition, in a subgroup of patients with histologically moderately differentiated tumors (N = 71), LEA.135-positive cases showed an improved O.S. (90.8 +/- 4.6% at 8 years; p < 0.001) compared with those who were LEA.135-negative (O.S. 55.6 +/- 13.6% at 8 years). The association remained statistically significant in a multivariable analysis after adjusting for histological grade, tumor size and age (p < 0.02). Thus, in this series of patients with lymph node-negative primary breast carcinoma, LEA.135 expression was associated with a significant decrease in the rate of recurrence and with an increase in overall survival, independent of tumor size, histologic grade, and patient's age. In contrast to the majority of other prognostic markers which predicts a worse biology, LEA.135 is a unique class of antigen whose expression indicates a lower aggressiveness of the tumor cells.

Aged↗