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Biomedical subjects

M M Grant

Publications and source records attributed to M M Grant.

At least 37 records · Page 2Linked to original sources

Effect of prostaglandin E1 infusion on leukocyte traffic and fibrosis in acute lung injury induced by bleomycin in hamsters.

OBJECTIVE: To determine whether the iv infusion of prostaglandin E1 (PGE1) could modify the early influx of neutrophils into bleomycin-injured lungs and if that would affect subsequent development of inflammation and fibrosis. BACKGROUND AND METHODS: In vivo controlled animal study performed in a university hospital pulmonary research laboratory. Male Syrian golden hamsters (100- to 110-g body weight) were divided into four treatment groups: a) No treatment; b) intratracheal bleomycin plus PGE1 infusion; c) bleomycin plus saline infusion; d) PGE1 infusion only. PGE1 (180 ng/hr.100 g) or saline were infused iv 3 to 25 hr after intratracheal instillation of bleomycin sulfate (0.5 U/0.5 mL.100 g). Total and differential counts of cells recovered by lavage, lavage fluid protein, and lung total protein and hydroxyproline levels were measured from 6 hr to 30 days later. RESULTS: PGE1 infusion reduced the influx of neutrophils 6 hr after bleomycin injury by 53% compared with saline infusion (p less than .0001), but increased inflammatory cell traffic after 24 hr for 15 days. At 4 days, protein recovered in lung lavage fluid was also decreased in PGE1-treated, bleomycin-injured animals, reflecting reduced injury to lung permeability barriers. Accumulation of lung collagen in the PGE1-treated, bleomycin-instilled hamsters tended to be lower than in the bleomycin-injured, saline-infused group at 15 and 30 days, although these differences did not achieve statistical significance. Despite this fact, greater than 33% of the animals in the PGE1-treated group died, possibly indicating an increased risk of sepsis in these animals. CONCLUSIONS: PGE1 infusion can decrease early neutrophil traffic and reduce injury to the lung permeability barriers. However, this treatment augments late inflammatory events and does not significantly alter the development of fibrosis.

Acute Disease↗

Characterization of Pseudomonas aeruginosa adherence to cultured hamster tracheal epithelial cells.

This study reports an in vitro system that allows the convenient study of both microenvironmental and bacterial factors affecting adherence of Pseudomonas aeruginosa to tracheal epithelium. Primary cultures of mixed ciliated and nonciliated epithelial cells isolated from hamster tracheas were grown on collagen-coated multiwell plates containing 10(5) epithelial cells/well at confluence. When 10(7) 14C-labeled P. aeruginosa (nonmucoid, strain Y-4) suspensions were added to each well, 8.13 +/- 2.6% (mean +/- SD) of the initial inoculum bound to the cultured cells, an amount comparable to that measured using suspensions of human tracheal epithelial cells and the same bacteria. The bacteria adhered preferentially to the cultured cells rather than to an acellular collagen matrix. Five additional nonmucoid strains of P. aeruginosa also bound well to the cultured cells, while two mucoid strains were less adherent. Strains of two other gram-negative bacteria, Pseudomonas maltophilia and Klebsiella pneumoniae, did not bind significantly, emphasizing the bacterial species specificity of the adherence interaction being measured. The binding interaction with P. aeruginosa was both pH-sensitive and altered by the presence of the divalent cation calcium. Thus, the in vitro assay system described provides a consistent surface of tracheal epithelial cells that binds P. aeruginosa in a specific manner and can be used to examine the effects of bacterial variables and microenvironmental conditions that may be present in the human airway.

Animals↗

Neutrophil-endothelial cell interaction in critical illness.

Sepsis syndrome frequently results in endothelial injury in many organ systems. To evaluate neutrophil-pulmonary endothelial cell interaction in the sepsis syndrome, we studied 39 critically ill patients prospectively and 20 normal volunteers. Thirteen patients with sepsis (mean age, 71.4 years), 14 patients in an intensive care unit control group (mean age 65.4 years), and 12 patients admitted with acute myocardial infarction (mean age, 66.8 years) were evaluated. Blood samples were drawn from septic patients within 24 hours and from ICU and MI patients within 72 hours of admission. All sepsis patients were culture positive, 6 of 13 from the blood. Both renal failure and ARDS developed in 54 percent of septic patients. 51Cr-labelled neutrophils were prepared and added to bovine pulmonary endothelial cell monolayers with and without added phorbol myristate acetate. Endothelial cells with adherent PMA and nonadherent PMN's, were harvested and radioactivity in each fraction measured with a gamma scintillation counter. Baseline and maximally stimulated (PMA, 3.0 ng/ml) neutrophil adherence to endothelial cells were similar in all patients groups. However, in septic patients, PMA-stimulated PMN adherence was reduced at lower doses, most significantly in those who developed ARDS within 24 to 48 hours of admission (p less than 0.05). Seventy-one percent of patients who developed ARDS had reduced stimulated adherence (PMA 1.0 ng/ml) compared to 22 percent of critically ill patients who did not. We conclude that diminished adherence of neutrophils to endothelium in response to low-level PMA stimulation is significantly more common in patients with sepsis who develop ARDS. Our findings suggest that PMN-endothelial cell interaction is altered by the time sepsis is clinically recognized but before the development of ARDS. We speculate that the observed reduction in adherence of the PMN to endothelial cells may be a consequence of down-regulation by mediators generated in the inflammatory response to sepsis and/or the need for active participation of septic endothelium in this interaction.

Aged↗

Defining the content domain of quality of life for cancer patients with pain.

This study identified attributes that define the content domain of quality of life in a sample of 41 cancer patients with chronic pain. Patients were asked four open-ended questions about the meaning of quality of life, what contributes to a good or poor quality of life, and how pain influences quality of life. Content analysis of responses revealed three categories of attributes that embrace the quality-of-life content domain. The first category is physical well-being. It includes general functioning and disease/treatment-specific attributes. The second is psychological well-being. It includes affective-cognitive attributes, coping ability, meaning of pain and cancer, and accomplishment attributes of quality of life. The third is interpersonal well-being. It incorporates social support and social/role functioning attributes. Replications of the current study in other groups of patients may yield data to support a two-part, multidimensional quality-of-life instrument. A norm-referenced measure can be used to evaluate quality of life in terms of attributes that are salient regardless of the disease or treatment. A domain-referenced measure may be used to evaluate attributes whose salience is dependent on specific disease, treatment, or life events.

Adaptation, Psychological↗

Production of lymphocyte chemokinetic activity by stimulated alveolar macrophages.

While the presence of a lymphocytic parenchymal infiltrate is characteristic of several lung diseases, the mechanisms responsible for the focal accumulation of lymphocytes within the lungs remain unclear. Since alveolar macrophages secrete several substances that affect lymphocyte function, we examined supernatants of stimulated, cultured guinea pig alveolar macrophages for their ability to alter lymphocyte motility. Guinea pigs were immunized by footpad injection of ovalbumin (OVA) emulsified in complete Freund's adjuvant. Fourteen days later, alveolar macrophages were obtained by bronchial lavage or teasing the lung parenchyma, enriched by adherence to plastic, and incubated for 3 and 24 hours in culture medium alone or medium containing either latex beads, OVA, or human serum albumin (HSA). Conditioned medium was harvested and assayed for chemoattractant activity against rat splenic lymphocytes in modified Boyden chambers. Regardless of stimulus, there was no evidence of enhanced lymphocyte motility above control values in supernatants harvested at 3 hours. At 24 hours, alveolar macrophages from OVA-sensitized guinea pigs stimulated with latex or OVA generated significant amounts of lymphocyte migration stimulating activity (LCA) (250 +/- 25 and 247 +/- 24 percent of control migration, respectively) compared to cells incubated in medium alone or with HSA (162 +/- 23 and 147 +/- 14 percent, respectively). Antigen recognition appears to be related to the presence of cytophilic anti-OVA antibody on the surfaces of alveolar macrophages of sensitized guinea pigs. LCA is resistant to neuraminidase, chymotrypsin, and heating to 56 degrees C, and was chemokinetic for T-lymphocytes. it elutes from Sephadex G-100 in two regions: one at approximately 67,000 d, and a second at approximately 15,000 d. These studies indicate that following systemic immunization, the guinea pig alveolar macrophage can react to specific antigen or phagocytosis of inert particulates by secreting a chemokinetic factor for T-lymphocytes, and may play a role in the pathogenesis of some types of antigen-induced lung disease.

Animals↗

Psychosocial aspects of artificial feeding.

Artificial feeding can have an impact on the patient's quality of life. The psychosocial problems commonly reported in relation to parenteral nutrition are distress from loss of normal eating ability, depression, body image changes, fear of problems with apparatus, and decreased sexual activity. The psychosocial problems most commonly reported in relation to enteral nutrition include gustatory distress , some physical distress , and tube-related distress . Results of teaching approaches to reduce patient discomfort during tube feeding indicate that sensory rather than coping behavior information is more likely to be associated with higher levels of perceived control over enteral feeding, and that perceived control rather than perceived coping ability is more likely to be associated with willingness to repeat the experience. In general, the studies reviewed suggest that enteral feeding may be less stressful and produce fewer psychosocial problems than parenteral nutrition.

Adolescent↗

Quality of life as a cancer nursing outcome variable.

A reliable and valid multidimensional instrument for measuring quality of life in cancer patients has been developed. Furthermore, a model has been offered that describes how quality of life works as an outcome variable. Using this model, predictions were made of how nursing interventions may directly or indirectly impact on quality of life. Initial testing of the model using data from 135 colostomy patients showed how satisfaction with nursing care and personal control act as cognitive mediators of self-worth, which then impacts on dimensions of quality of life.

Body Image↗

The lipid interstitial cell of the pulmonary alveolus. Age and species differences.

We have previously shown that alveoli of neonatal rat lungs contain 2 morphologically distinct fibroblasts; 1 that contains lipid droplets and 1 that does not. We have named these lipid interstitial cells (LIC) and nonlipid interstitial cells (NLIC). In this study, using stereologic methods, we evaluated the distribution of LIC and NLIC in the alveoli of immature and mature rats, hamsters, and mice and quantitated cytoplasmic lipid in the LIC. We found that fibroblasts account for approximately 50% of resident alveolar wall cells in immature and 20% in mature rodent lungs. At each age LIC accounted for half of the fibroblasts. There were age and species differences in the amount of LIC lipid. The volume density of cytoplasmic lipid was higher in immature rats (0.285) than in mice (0.205) or hamsters (0.010) and was higher in mature mice (0.176) than in hamsters (0.051) or rats (0.019). Possible explanations for these differences are discussed. Bundles of characteristic cytoplasmic myofilaments established that the LIC was identical to the previously described contractile interstitial cell of the lung. These studies confirm the presence of 2 distinct fibroblasts in the alveoli of immature and mature rodents of several species.

Aging↗

Development of macrophages in the lungs of fetal rabbits, rats, and hamsters.

Fetal rabbits (days 13-32), rats (days 14-22), and hamsters (days 11-15) and selected postnatal animals were examined for pulmonary macrophages or their precursors in 2-micron sections stained by PAS-lead hematoxylin (all species), electron micrographs (rabbit and rat), and cytochemical incubations for acid phosphatase (rabbit and rat), aliesterase, and N-acetyl glucosaminidase (rabbits). All methods revealed macrophages in perinatal specimens. The appearance and distribution of these cells were compared in the different preparations to establish the reliability of PAS-lead hematoxylin for identifying them in less developed fetal lungs, where they are less active for lysosomal enzymes the earlier the stage examined. In the sections, macrophages are seen to possess a round or indented nucleus, an irregular contour, and a deep purplish-gray cytoplasm containing a variety of pink PAS-stained granules, equated with heterolysosomes by ultrastructural cytochemistry. In less developed lungs, macrophages occur along with putative precursors having a more rounded outline and fewer PAS-stained granules. In pseudoglandular lungs these precursors predominate over rather vacuolated macrophages resembling Hofbauer cells. In all three species both cell types first appear in the stroma during the bronchial bud stage and are frequently seen to divide from that time on. The earliest precursors have a relatively sparse cytoplasm which later increases in daughter cells. Hofbauer-like cells disappear during the canalicular stage of development, replaced by macrophages and transitional forms from the more rounded precursors. In day 21 rabbit lungs, scattered stromal cells are reactive for aliesterase, and, some days later, for acid phosphatase and glucosaminidase. Free mononuclear cells are rare in airways of pseudoglandular lungs but become common later. A day or two before birth in rats, free cells range between rather undifferentiated leukocytes to typical macrophages, but cells with the macrophage's complete repertory of inclusions are seen only after birth. In the fetus, typical monocytes were not identified in either the pulmonary stroma or the airways. A replicating population of macrophage-like cells therefore resides in fetal lungs. It is established before bone marrow is formed and, in rats, before monocytes have appeared in the circulation.

Animals↗

Influence of maternal diabetes on basement membranes, type 2 cells, and capillaries in the developing rat lung.

To determine the effect of maternal diabetes on rat lung development, we studied the ultrastructure of the alveolar wall from the ninteenth day of gestation (term = 22 days) through the eighth postnatal day in fetal and neonatal rats of mothers with streptozotocin-induced diabetes. In normal fetal lung development, epithelial basement membranes develop large discontinuities beneath type 2 cells, through which cytoplasmic foot processes extend into the interstitium. Maternal diabetes delays the appearances of these epithelial basement membrane discontinuities and reduces the number of type 2 cell processes that penetrate it. These alterations in epithelial basement membrane are reversed after birth. There is no ultrastructural evidence of a delay in type 2 cell maturation as assessed by lamellar body volume density morphometry. Endothelial basement membranes, which are not present around the growing pulmonary capillary bed in the pseudoglandular lung, are seen late in normal gestation, primarily around capillaries forming the mature air-blood barrier. This development of endothelial basement membrane may be delayed in the fetuses of diabetic mothers and reflects a significant delay in the expansion of the pulmonary capillary network in these animals as assessed by morphometric volume density measurements. This effect on capillary growth is not reversed in the newborn animals through 8 days after birth. The summation of these effects indicates a generalized slowing of fetal lung development by maternal diabetes, some of which effects persist after birth and may continue to influence lung development during the period of postnatal alveolar septal growth.

Animals↗

Quality of life index for patients with cancer.

The purpose of this study was to develop an instrument for measuring the quality of life of cancer patients. Quality of life was measured with 14 linear analogue scale items concerning general physical condition, normal activities, and personal attitudes on general quality of life. The tool was tested with four subject groups: oncology outpatients receiving chemotherapy (43) or radiation therapy (39), oncology inpatients receiving chemotherapy (48), and nonpatient volunteers (48). Test-retest reliability coefficients for these samples ranged from r = .11 to .97, with 52 of the 56 possible r's greater than .60, p less than .01; internal consistency was .88, p less than .01. Construct and discriminant validity were indicated, while concurrent validity between quality of life scores and physician estimates of Karnofsky ratings, prognosis, and quality of life were poor.

Adult↗

Alterations in lung basement membrane during fetal growth and type 2 cell development.

We studied basement membrane development in the late fetal and in the neonatal rat lung, from the 18th day of gestation (term = 22 days) through the 8th postnatal day, with particular emphasis on the gas-exchange region of the lung. In the periphery of the lung, as type 2 cells differentiate, the continuous basement membrane develops openings beneath these cells. Basal cytoplasmic foot processes extend through these discontinuities into the underlying interstitium, often approaching interstitial cells closely. These discontinuities and extensive foot processes are associated only with type 2 epithelial cells and not with either differentiated airway cells or with the type 1 alveolar lining cells derived from type 2 cells. The type 2 cell basement membrane discontinuities and penetrating foot processes are maximal in the perinatal period and decrease in the week after birth. The appearance of openings in type 2 cell basement membrane and changes in distribution, linear density, and ruthenium red staining of anionic sites suggest that the epithelial basement membrane undergoes continuous remodeling throughout development, particularly in association with type 2 cell differentiation and growth of lung surface area. Epithelial cell foot processes may interact with underlying interstitial cells and affect the coordination of lung surface growth with the development of its connective tissue framework.

Animals↗

Quality assurance programme for nursing.

This article describes a conceptual and methodological framework for evaluating nursing care quality. The conceptual framework is based on Orem's theory of self-care which emphasizes the importance of decisions in the selection of nursing process based on patient status and problems. The primary outcome criteria is self-care. The methodological framework is based on Greenfield's criteria maps methodology for linking patient status (problems or diagnoses) to decisions about nursing interventions and linking these specific nursing intervention criteria to desired outcomes for self-care. The article further describes a multiagency quality assurance programme for nursing. The programme includes: a definition of criteria and standards across agencies; nursing care management protocols that define standards of care; continuing education courses for nursing based on management protocols; the maps method of auditing actual and recorded nursing process and patient outcomes as defined in the management protocol.

Humans↗

Development of neuroepithelial bodies in fetal rabbit lungs. I. Appearance and functional maturation as demonstrated by high-resolution light microscopy and formaldehyde-induced fluorescence.

Developing lungs of fetal rabbits aged 13 days through early postnatal stages were examined for periodic acid-Schiff (PAS)-lead hematoxylin staining, serotonin fluorescence, and argyrophilia, methods selective for small-granule (neuro) endocrine cells. Later stages were also studied by electron microscopy. These cells arise from precursors that first appear around days 18-19 in the endodermal epithelium; the latter stand out as clear cells from their undifferentiated, glycogen laden neighbors. The cells first form in the main and lobar bronchi, then continue to arise in the lining of newly laid down branches of the extending bronchial tree, tending to concentrate near points of branching. Some cells have been seen to divide, and clusters of two, four, or more soon appear. Morphologically mature neuroepithelial bodies begin to appear in larger bronchi around 23 days, although the largest examples occur in 25-day and older fetuses. After 23 days, additional bodies mature from clear-cell precursors in more recently laid down distal lung, so that by the terminal sac period (around days 28-29) all conducting airways contain them, and the clear cells and clear-cell clusters have virtually disappeared. A pinkish staining by PAS-lead hematoxylin and dense-core secretory granules, which begin to appear in the clear cells, are present in mature small-granule cells whether solitary or aggregated. Argyrophilia is less consistently demonstrable. Fluorescence for serotonin is first evident in mature neuroepithelial bodies at 23 days, increases considerably by 26 days, and reaches a prenatal peak around days 28-29, when neuroepithelial bodies and solitary small-granule cells along the whole conducting bronchial tree may participate. Fluorescence appears to decrease during days 30-31 but strengthens again after birth. Composed of these solitary small-granule cells and neuroepithelial bodies, the pulmonary APUD system of rabbits thus appears substantially functional during the final quarter of gestation.

APUD Cells↗