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Biomedical subjects

R Dahl

Publications and source records attributed to R Dahl.

At least 199 records · Page 11Linked to original sources

Severe destruction of esophageal nerves in a patient with achalasia secondary to gastric cancer. A possible role of eosinophil neurotoxic proteins.

We present a case of secondary achalasia due to an adenocarcinoma of the stomach with no tumor infiltration of the esophagus. Immunohistochemical staining revealed a massive infiltration of activated eosinophils in the muscularis of the esophagus with secretion of the highly cytotoxic and neurotoxic eosinophil cationic protein (ECP). Immunohistochemical staining for the neuropeptides VIP and substance P, as well as the histochemical demonstration of AChE, revealed a nearly total absence of all three neurotransmitters/modulators compared to control. The hypothesis is advanced that eosinophil neurotoxicity is the cause of secondary achalasia.

Adenocarcinoma↗

Eosinophil infiltration in primary esophageal achalasia. A possible pathogenic role.

Smooth-muscle specimens from the lower esophagus of nine patients operated on for esophageal achalasia were examined with routine hematoxylin-eosin staining. This procedure revealed only a few eosinophils in or between the external smooth-muscle layers. Using specific immunohistochemical methods for the detection of the eosinophil cationic protein (ECP), however, varying degrees of eosinophil infiltration and extracellular deposit of ECP were disclosed in the achalasia specimens. The ECP also reacted with the monoclonal antibody, EG2, indicating secretion of the cytotoxic ECP. Few or no eosinophils were seen in the muscularis externa in specimens from six control patients without esophageal disease. In two controls many eosinophils were observed in the muscularis externa. However, no extracellular ECP was detected and very few eosinophils reacted with the monoclonal antibody (EG2), suggesting that these eosinophils were not activated. Depletion or total absence of peptidergic innervation was seen in all achalasia specimens but not in controls. Since the eosinophil cationic protein (ECP), in its activated form, is cytotoxic, we propose a pathogenic role of the eosinophil infiltration in achalasia.

Adult↗

Neutrophil and eosinophil involvement of the small bowel in patients with celiac disease and Crohn's disease: studies on the secretion rate and immunohistochemical localization of granulocyte granule constituents.

PURPOSE: The concentrations of myeloperoxidase (MPO), a neutrophil granule constituent, and eosinophil cationic protein (ECP), a specific eosinophil granule protein, were measured in jejunal perfusion fluid in an attempt to elucidate the neutrophil and eosinophil involvement of the small bowel in health and disease. PATIENTS AND METHODS: The control group consisted of 14 males and two females. Ten patients (seven males and three females) with Crohn's disease and seven patients (two males and five females) with celiac disease were also studied; in addition, one patient with relapsing giardiasis, one patient with giardiasis and complete absence of plasma cells in small intestinal lamina propria, and one patient with selective IgA deficiency and no IgA plasma cells in duodeno-jejunal lamina propria were evaluated. Segmental perfusion of the jejunum was performed according to a previously described method. MPO and ECP were measured by radioimmunoassays. RESULTS: In healthy control subjects, the concentrations of both granule proteins were in a narrow range and much higher than would have been anticipated from passive leakage from circulating blood. In patients with celiac disease, the perfusion fluid concentrations of MPO and ECP were on average 3.5 and eight times, respectively, higher than the values seen in the controls. The jejunal segment perfused in patients with Crohn's disease was endoscopically and histologically normal. The perfusion fluid concentrations of MPO and ECP were increased 3.5 and two times, respectively, compared with that in the control subjects. Both patient groups and the control group had similar perfusion fluid concentrations of albumin. Data on MPO and ECP expressed as jejunal secretion rates gave the same differences between patients and controls as just described for the jejunal fluid concentrations. Immunohistochemical studies of jejunal biopsy specimens from another group of patients with celiac disease demonstrated a prominent extracellular deposit of ECP in the lamina propria of the atrophic intestinal mucosa, whereas the release of neutrophil constituents (cathepsin G, MPO) was scarce. In Crohn's disease, an extracellular degranulation of ECP and, to a lesser extent, of cathepsin G was observed in relation to ulcerations only. CONCLUSION: Data obtained indicate that the local release of neutrophil and eosinophil granule components is enhanced in the jejunal tissue from patients with celiac sprue and Crohn's disease. The prominent extracellular deposit of eosinophil granule constituents with cytotoxic properties at the site of inflammatory intestinal lesions in celiac sprue might reflect a pathophysiologic mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Nocturnal asthma: effect of treatment with oral sustained-release terbutaline, inhaled budesonide, and the two in combination.

The purpose of this study was to compare effect of treatment with an oral long-acting beta 2-agonist (sustained-release terbutaline, Bricanyl depot), an inhaled steroid (budesonide, Pulmicort), and the combined treatment in patients with nocturnal asthma. Thirty-seven patients completed the study. During a 1-week run-in period with inhaled terbutaline monotherapy, the mean nocturnal asthma score was 1.0 (+/- 0.1) (corresponding to one awakening every night), and the mean overnight fall in peak expiratory flow rate was 27.7% (+/- 2.0). The patients were randomly entered into double-blind, crossover periods of 3 weeks each: (1) sustained-release terbutaline, 10 mg twice daily (b.i.d.), (2) sustained-release terbutaline, 10 mg b.i.d., and two puffs (400 micrograms) of budesonide, b.i.d., and (3) two puffs (400 micrograms) of budesonide, b.i.d. The combined treatment resulted in significantly lower overnight fall in peak expiratory flow rate (6.9% +/- 1.4 compared to 9.4% +/- 2.0 during sustained-release terbutaline and 10.4% +/- 1.9 during budesonide) and less nocturnal awakenings (nocturnal asthma score 0.15 +/- 0.05, 0.43 +/- 0.09, and 0.26 +/- 0.06, respectively) than either single treatment alone (p less than 0.05). The differences between the single treatments were not significant. We thus found that an inhaled steroid is as effective as a long-acting oral beta 2-agonist in controlling nocturnal asthma and that the combination is better. The observed differences were, however, small, and other studies would be required to evaluate the clinical significance of the present finding.

Administration, Inhalation↗

The formation of eosinophil and neutrophil chemotactic activity during a pollen season and after allergen challenge.

Heat-stable (HS) and heat-labile (HL) neutrophil chemotactic activities (NCAs) have been demonstrated in serum after allergen challenge of subjects with asthma. In this investigation, we have studied the possible occurrence of similar activities in 20 atopic individuals on natural exposure to allergen, that is, during the birch-pollen season. Since eosinophil accumulation is a hallmark of an ongoing allergic inflammation in the respiratory tract also, the possible production of eosinophil chemotactic activity (ECA) was examined in serum after allergen challenge and at natural exposure to pollen. Both HL-NCA and HL-ECA were produced to a significant extent (p less than 0.001) during the season, with the peak of activities occurring simultaneously with the peak pollen count. HL-ECA was produced after allergen challenge of subjects with asthma in the laboratory, as has been demonstrated for NCA previously. The activity of the HS-NCA was unaltered during season. Gel-filtration studies of the major HL-NCA and HL-ECA indicated a molecular weight for both activities of 100 to 150,000, and the activities produced during season cochromatographed with the HL-NCA and HL-ECA produced after allergen challenge in the laboratory, suggesting that all these activities are due to one and the same molecule. The results suggest that the heat-labile chemotactic activity found in serum of atopic subjects and subjects with asthma after allergen exposure may be involved in the attraction of eosinophils and neutrophils to the site of allergic inflammation.

Asthma↗

Nitrate and nitrite concentrations in human saliva: variations with salivary flow-rate.

Salivary nitrate concentration has often been used as a measure of human intake of nitrate. However, our findings indicate that this is not a reliable indicator because the nitrate concentration varies with salivary flow-rate and thus depends on the sampling procedure. Parotid or whole saliva was collected from up to six volunteers under carefully controlled conditions. The effects of stimulating saliva production by chewing on silicon tube (mechanical stimulation) or by sucking citric acid from cotton wool (gustatory stimulation) were investigated. Chewing decreased the average nitrate (plus nitrite) concentration in whole saliva by 59% and the nitrate concentration in parotid saliva (which does not contain nitrite) by 53%, relative to unstimulated saliva. Citric acid stimulation decreased the average parotid salivary nitrate concentration by 88%. Stimulation of salivary secretion increased the total salivary nitrate output and the extent of reduction of nitrate to nitrite for most subjects. The unstimulated parotid salivary nitrate concentration was, on average, 2.8 times the nitrate plus nitrite concentration in unstimulated whole saliva.

Adult↗

Lung function and postural changes during pregnancy.

The aim of this study was to determine the effects of postural changes on lung function in pregnant women during the first, second, third trimester and post partum. A significant decrease in FRC, PEF and FEV1 was observed as a result of the postural changes. Arterial oxygenation, MVV and DLCO remained largely the same.

Adult↗

Cortisol secretion in adolescents with major depressive disorder.

Plasma cortisol concentrations were determined every 20 min for 24 h, in a nonstressful environment, among 48 rigorously assessed, mostly outpatient, drug-free adolescent subjects during an episode of major depression (MDD) and among 40 normal adolescent subjects. There were no significant differences in the 24-h mean, peak, or nadir, or the time of the nocturnal rise, in plasma cortisol in the 2 groups. Analyses of different subgroups of MDD adolescents according to suicidality, severity of depression, separation anxiety, psychotic subtype, endogenicity, duration of episode, and sex also revealed no significant group differences. Only one adolescent (with MDD) was identified clearly as a hypersecretor of cortisol. These results indicate that abnormalities of spontaneous cortisol secretion are an unusual finding among adolescents with major depression when studied in a nonstressful environment.

Adolescent↗

Lung function and bronchial reactivity in farmers.

The purpose of this study was to evaluate the prevalence and type of lung function disorders in Danish farmers. Three samples of farmers were drawn from a group of unselected farmers who had participated in an epidemiological study. Group I (47 persons) was a sample of the 8% of all farmers who had reported that they had asthma; group II (63 persons) was a sample of the 28% of farmers who had had wheezing, shortness of breath, or cough without phlegm; and group III (34 persons) a sample of the farmers (64% of the total) who had no asthma and no respiratory symptoms. The farmers with symptoms (groups I and II) had low mean levels of FEV1 and high values for residual volume, whereas the symptomless farmers had normal lung function and no airways obstruction. The proportion of farmers with an FEV1 below the 95% confidence limit for predicted values was 43% in group I and 23% in group II; there were none in group III. Bronchial hyperreactivity to histamine occurred in 96% of asthmatic farmers, 67% of farmers with wheezing or shortness of breath, and 59% of symptomless farmers. A low level of FEV1 was associated with the number of years in pig farming and bronchial hyperreactivity in group II but not group I or III. Most of the bronchial hyperreactivity was explained in the multiple regression analysis by a low FEV1, though this was significant only for farmers in group II. Thus farmers who reported asthma, wheezing, shortness of breath, or a dry cough in general had airways obstruction with an increased residual volume, whereas symptomless farmers had normal lung function. Severe bronchial hyperreactivity was mostly explained by a diagnosis of asthma and poor lung function, though some farmers with normal lung function and no respiratory symptoms had increased bronchial reactivity.

Adult↗

Anthropometric design criteria: correction variables for military aircraft.

Significant errors in the application of dimensional anthropometric design criteria for tactical military aircraft cockpits have been identified. These errors result from insufficient consideration of previously undefined variables relative to posture, restraint system items, and aviators' personal protection equipment as discussed by McConville and Laubach in 1978.

Adult↗

Are blood eosinophil number and activity important for the development of the late asthmatic reaction after allergen challenge?

A role for eosinophils in chronic asthma has recently gained substantial support. We hypothesized that in addition to eosinophil chemoattractants released in the lung, the availability of a sufficient number of blood eosinophils to be recruited and their increased activity are prerequisites for the development of asthma. To test this hypothesis the blood eosinophil number and serum levels of ECP (eosinophil cationic protein were measured before allergen challenge of 13 allergic asthmatics. Each individual was pretreated with either placebo or four inhalant anti-asthmatic drugs at random and blind in order to modulate the late asthmatic reaction (LAR). Irrespective of premedication the blood eosinophil number and serum-ECP levels were significantly higher before challenge when the challenge resulted in LAR. Only corticosteroids abrogated the development of LAR and also significantly reduced eosinophil activity as measured by serum-ECP. Thus the inherent activity of a sufficient number of eosinophils may be important determinants for the expression of allergic asthma.

Adult↗

Characterization of ischemia-induced loss of epithelial polarity.

Total renal ischemia for various time intervals (0-50 min) resulted in the rapid and duration-dependent redistribution of polarized membrane lipids and proteins in renal proximal tubule cells. Following only 15 min of ischemia, apical membrane enrichment of NaK-ATPase, normally a basolateral membrane (BLM) enzyme, had increased (1.6 +/- 0.6 vs. 2.9 +/- 1.2, P less than 0.01). In vivo histochemical localization of NaK-ATPase showed reaction product throughout the apical microvillar region. PTH-stimulatable adenylate cyclase, another BLM protein, was also found in ischemic but not control apical membrane fractions. One dimensional SDS-PAGE showed four bands, present in control BLM and ischemic apical membranes, which could not be found in control apical membrane fractions. Immunohistochemical localization of leucine aminopeptidase (LAP) showed the enzyme was limited to the apical domain in control cells. Following ischemic injury (50 min), LAP staining could be seen within the cell and along the BLM. Following 24 hr of reperfusion, the BLM distribution of LAP was further enhanced. With cellular recovery from ischemic injury (5 days), LAP was again only visualized in the apical membrane. Duration-dependent alterations in apical and BLM lipids were also observed. Apical sphingomyelin and phosphatidylserine and the cholesterol-to-phospholipid ratio decreased rapidly while apical phosphatidylcholine and phosphatidylinositol increased. Taken together, these results indicate renal ischemia causes rapid duration-dependent reversible loss of surface membrane polarity in proximal tubule cells.

Adenylyl Cyclases↗

Terbutaline sustained-release tablets in nocturnal asthma--a placebo-controlled comparison between a high and a low evening dose.

The effects of oral treatment with terbutaline sustained-release (SR) tablets (Bricanyl Depot) were studied in nine patients who had bronchial asthma and marked diurnal variation in ventilatory function. In a randomized and double-blind study, the patients were treated with terbutaline SR 7.5 mg b.i.d., terbutaline SR 7.5 mg in the morning and 15 mg in the evening and terbutaline SR placebo b.i.d. Each treatment was given for 1 week. The nocturnal decline in the peak expiratory flow rate (PEFR) was 45% during the placebo period, 27% after the lower and 22% after the higher terbutaline SR evening dose (P less than 0.01 for both treatments compared to placebo). The mean morning PEFR was significantly higher with the high evening dose than with the low evening dose (P less than 0.01). Mild to moderate side effects were noted. The sustained-release preparation of terbutaline seems to be of clinical value in preventing or relieving nocturnal asthma and early morning dipping. The flexible dose technique, with a higher evening dose, results in further improvements in these patients.

Adult↗

A possible role of the dietary fibre product, wheat bran, as a nitrite scavenger.

We found that wheat bran acted as a nitrite scavenger under conditions similar to those that exist in the stomach. Wheat flour and cellulose did not act as nitrite scavengers. Wheat bran, at a concentration equivalent to that in the stomach after ingestion of about two pieces of whole-wheat bread, reduces the nitrite concentration from 20 microM to about 10 microM in 60 min at pH 3.5 and 37 degrees C. At pH 2.5 and 1.5, most of the nitrite had disappeared in 10 min. At pH less than or equal to 2.5 the nitrite scavenging effect of bran was as efficient as that of ascorbic acid. Ferulic acid, a component of bran, reacted rapidly with 20 microM-nitrite both at pH 3.5 and 1.5, whereas phenolic lignin model compounds only reacted at pH 1.5.

Ascorbic Acid↗

Lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate in delayed type hypersensitivity.

A skin window technique was used to study the morphology of leucocytes in upper dermis and exudate during nickel challenge in patients with contact allergy to nickel. Contact allergic patients and healthy volunteers tested with a skin widow without addition of nickel to the chamber medium served as controls. The morphology of the leucocytes in dermis was studied in biopsies taken 8, 24, or 48 h after skin window application, and in a parallel test the morphology of the exudate was examined by sequential collection of the chamber medium during a 48 h period. The infiltrate in dermis of contact allergic patients with nickel challenge in the chamber medium showed a time-dependent increase of mononuclear cells, eosinophils and basophils and a concomitant decrease of polymorphonuclear granulocytes, characteristic of a combined specific and unspecific inflammation. The morphology of the exudate in contact allergic patients exposed to nickel showed a dominance of polymorphonuclear granulocytes throughout the study period, while mononuclear cells, eosinophils and basophils were detected at a much lower quantity and with a considerable delay. Further, we studied the kinetics of the leucocyte granule proteins: lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate fluid in a parallel test. A significant higher flux was found for all during the second day of allergen exposure compared to contact allergic patients without allergen challenge as well as normal volunteers. The increased protein fluxes were not accompanied by an increased flux of polymorphonuclear granulocytes in the exudate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗