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Biomedical subjects

M Kraft

Publications and source records attributed to M Kraft.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparative study of extended release albuterol sulfate and long-acting inhaled salmeterol xinafoate in the treatment of nocturnal asthma.

BACKGROUND: Nocturnal worsening of asthma is a common problem in asthma and is associated with increased morbidity and mortality. Long acting beta-2 agonists are considered long-term symptom control medications, especially for nocturnal symptoms. OBJECTIVE: To compare efficacy of an extended release oral beta-2 agonist, albuterol sulfate (Volmax), to a long-acting inhaled agent, salmeterol (Serevent) in the treatment of nocturnal asthma. METHODS: This was a multicenter double-blind, double-dummy, randomized, crossover design with a 1-week baseline period and two 3-week treatment periods separated by a 7 to 9-day washout. An optional 2-week, open-label phase was conducted to evaluate patient preference. RESULTS: A total of 46 patients were included in the efficacy analysis. For the primary outcome variable of morning peak expiratory flow, there were similar and significant improvements over the 3-week treatment period for both medications compared with baseline (P < .001). Similar improvements were seen in the overnight change in PEF values (P < .001). The morning and overnight changes in FEV1 were not significantly different between treatment arms (P > .05). There were significant improvements in both treatment periods in regard to the percentage of nights without awakenings (baseline 53.6+/-5.3%), extended release albuterol 83.3+/-3.0% (P < .001), and salmeterol 88.8+/-2.4%. The percentage of patients who had no awakenings during treatment did not differ significantly for the two medications. Both treatments also resulted in a decrease in the use of rescue albuterol (extended release 2.66+/-0.35 puffs per day, salmeterol 1.85+/-0.29) from baseline (4.57+/-0.41, P < .001). There was a significant difference between groups (P = .001). The reasons why patients preferred one medication over the other varied. CONCLUSION: Both extended release albuterol tablets and inhaled salmeterol resulted in similar bronchodilation and good control of nocturnal asthma symptoms.

Administration, Inhalation↗
PubMed1999

Interleukin (IL)-13 and IL-4 are potent inhibitors of IL-8 secretion by human intestinal epithelial cells.

Intestinal epithelial cells are able to produce soluble mediators that initiate or amplify inflammatory events in the intestinal mucosa. Interleukin (IL) -8 is suggested to be a cytokine playing a major role during the acute and chronic processes in inflammatory bowel disease (IBD). TH-2 cytokines have been described as down-regulating the inflammatory response. We analyzed the effects of IL-10, IL-13, and IL-4 on IL-8 secretion in intestinal epithelial cells. The human colonic epithelial cell line Caco-2 and freshly isolated intestinal epithelial cells were used. Cells were stimulated with IL-1beta after treatment with TH-2 cytokines. Levels of IL-8 were determined by employing enzyme-linked immunosorbent assay (ELISA). Stimulation with IL-1beta results in a time-dependent IL-8 secretion. The addition of IL-4 and IL-13, but not IL-10, to activated epithelial cells resulted in a strong decrease in IL-8 secretion. Maximal inhibition required that TH-2 cytokines be added up to 60 min before or simultaneous with stimulatory agents. We present novel findings that IL-4 and IL-13 strongly down-regulate IL-8 secretion from intestinal epithelial cells. A microenvironment containing high concentrations of IL-4 and IL-13 may alter the recruitment of immune cells to enterocytes at least partly by inhibiting IL-8 production. This inhibition might diminish the severity of the intestinal inflammatory response and, thus reduce clinical disease activity.

Caco-2 Cells↗
PubMed1999

Interleukin-15 strongly inhibits interleukin-8 and monocyte chemoattractant protein-1 production in human colonic epithelial cells.

Interleukin-15 (IL-15) is a novel cytokine with actions similar to IL-2 because of common receptor components. Although IL-15 is expressed in colonic epithelial cells and may regulate epithelial cell function, its effects on these cells are not fully defined. We explored the regulatory effects of IL-15 on IL-8 and monocyte-chemoattractant protein-1 (MCP-1) production in the colonic epithelial cell line Caco-2 as well as in freshly isolated human colonic epithelial cells. IL-15 was added to intestinal epithelial cells under various culture conditions. Levels of chemokines were determined by enzyme-linked immunosorbent assay. To determine the elements of the IL-2/IL-15R complex involved we used neutralizing antibodies specific for individual receptor chains. IL-15 down-regulates IL-8 and MCP-1 production in Caco-2 cells as well as in freshly isolated human colonic epithelial cells in a dose-dependent manner. Intestinal epithelial cells became more responsive to IL-15-induced suppression when activated with greater IL-1 doses. Strong chemokine suppression was seen when IL-15 was given prior to, simultaneous with, or after stimulatory agent. Anti-IL-2Rgamma antibodies efficiently blocked (82% inhibition) the suppression induced by IL-15, while anti-IL-2Rbeta antibodies were less effective. The involvement of beta-chain was further suggested by the finding that a mixture of both monoclonal antibodies (mAb) at a suboptimal concentration (1 microgram/ml of each mAb) produced a synergistic inhibitory effect on down-regulation of epithelial chemokine production. These results show that IL-15 can suppress IL-8 and MCP-1 secretion by intestinal epithelial cells. A microenvironment containing high concentrations of IL-15 may alter the recruitment of neutrophils to enterocytes at least partly by inhibiting IL-8 and MCP-1 production.

Antibodies, Monoclonal↗
PubMed1999

Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma.

We have shown in nocturnal asthma that alveolar tissue eosinophils are increased at night as compared with the proximal airway, and that they correlate with the overnight decrement in lung function. As the CD4+ cell is thought to be the principal orchestrating cell in eosinophil recruitment, we evaluated its presence in the proximal and distal airways in nocturnal asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and at 4:00 A.M. separated by 1 wk. Immunohistochemical staining and morphometric analysis were used to determine the number of CD3+, CD4+, and CD8+ cells and EG2+ eosinophils per mm2 in the epithelium, lamina propria, and alveolar tissue. At 4:00 A.M., the NA group had a significantly greater number of CD4+ cells in the alveolar tissue than the NNA group (9.8 cells/ mm2 [5.6-30.8, interquartile (IQ)] versus 1.5 cells/mm2 [0-6. 3, IQ], p = 0.04). Within the NA group, there were significantly greater numbers of CD3+, CD4+, CD8+, and EG2+ cells in the proximal airway lamina propria than in the distal airway at both 4:00 P.M. and 4:00 A.M. There were no differences within the epithelium between the groups at either time point. Only alveolar tissue, not airway tissue, CD4+ cells correlated inversely with the percentage predicted FEV1 at 4:00 A.M. (r = -0.68, p = 0.0018) and positively with the number of alveolar tissue EG2+ cells (r = 0.66, p = 0.01). These findings suggest that the CD4+ lymphocyte is increased in the alveolar tissue at night in nocturnal asthma as compared with non-nocturnal asthma.

Adult↗
PubMed1999

The distal airways: are they important in asthma?

Although the airways of <2 mm in diameter have been dubbed the "quiet zone", they do not appear to be so in asthma. Physiological and pathological evidence suggests that the small airways and lung parenchyma participate in asthma pathogenesis, and may explain many of the clinical observations noted. This review presents this evidence, beginning with physiological evidence, followed by pathology and last by imaging studies that evaluate the distal lung. Seminal physiological studies date back to the 1960s, with significant progress in the area of airway smooth muscle and its contribution to airways responsiveness noted over the last several years. The use of bronchoscopy in clinical studies has complemented the autopsy studies in advancing knowledge about airway structural changes appreciated in asthma in the small airways and lung parenchyma. These pathological studies have allowed validation of the physiological, and more recently the imaging studies performed to evaluate this compartment of the lung in asthma. Thus, the evidence suggests that the small airways and parenchyma contribute significantly to asthma pathogenesis. The challenge now lies in evaluating this compartment in the context of its value as a therapeutic target in asthma.

Airway Resistance↗
PubMed1999

Corticosteroids and leukotrienes: chronobiology and chronotherapy.

Corticosteroids and leukotrienes play opposite roles in asthma. Corticosteroids, both endogenously secreted and exogenously administered, are antiinflammatory and are very effective in the treatment of asthma. They have also been evaluated chronotherapeutically and have been found to be very effective in reducing the enhanced airway inflammation and decrement in lung function associated with nocturnal worsening of asthma. Leukotrienes are potent proinflammatory and spasmogenic mediators that have been shown to be increased at night in patients with nocturnal asthma (NA). Leukotriene modifiers, a new class of medications to treat asthma, improve, but do not abolish, the symptoms and decrement in lung function associated with nocturnal asthma. However, they have not been evaluated chronotherapeutically. This article addresses the roles of corticosteroids and leukotrienes in nocturnal asthma and their position as therapeutic agents or targets for therapy.

Adrenal Cortex Hormones↗
PubMed1998

Influence of different trocar tips on abdominal wall penetration during laparoscopy.

Most trocars currently used to place a cannula through the abdominal wall have a conical or pyramidal tip. Because the risk of inadvertent injury along with removal of the cannula is probably related to (a) the force needed to traverse the abdominal wall, (b) the force needed to remove the trocar, and (c) the defect in the abdominal wall, the optimum configuration of the penetrating tip should be determined. The entry force needed to perforate the abdominal wall, the removal force necessary to remove the trocar, and the defect in the abdominal wall were measured in a porcine model under standardized conditions (general anesthesia, 12 mmHg pneumoperitoneum). Nineteen trocars (six disposable, seven reusable, six custom-made) have been tested. They were divided into six groups according to the shape of the tip (conical, pyramidal, or a combination). The entry force (F = 25.6, p < 0.0001) and the removal force (F = 5.1, p < 0.01) were related to the shape of the tip. Conical tips needed a higher force than purely pyramidal tips. The abdominal defect was also different between groups (F = 6.5, p < 0. 001). The trocar with a pyramidal shape caused a greater defect than conical tips. The defect in the abdominal wall was inversely related to the entry force (r = -0.55, p < 0.001) and to the removal force (r = -0.57, p < 0.001). There is not an optimum configuration of a simple push-through trocar with a low entry force and a high removal force. Some kind of a conical tip is recommended for insertion of trocars under direct view.

Abdominal Muscles↗
PubMed1998

Expression of epithelial markers in nocturnal asthma.

BACKGROUND: Although the airway epithelium participates in inflammation and repair, the circadian expression of epithelial cell markers involved in these processes has not been investigated. OBJECTIVE: We sought to determine whether expression of CD51 (vitronectin and fibronectin receptor), CD54 (intercellular adhesion molecule-1), HLA-DR (activation marker), CD29 (beta1 integrin), CD49b (collagen receptor), and CD11b (complement receptor) exhibit a circadian rhythm in asthma. METHODS: Eleven patients with nocturnal asthma (NA), 9 subjects with nonnocturnal asthma (NNA), and 10 control subjects underwent bronchoscopy at 4 PM and 4 AM in a random order 1 week apart, with brushing of the proximal and distal airways. The percentage of cells staining for a particular marker was determined. RESULTS: At 4 PM, HLA-DR in the proximal airways and CD54 in the distal airways was significantly greater in control subjects as compared with asthmatic subjects (HLA-DR, control subjects: 10.0% [range, 5.0% to 21.0%]; NNA: 8.0% [range, 4.0% to 14.5%] NA: 3.5% [range, 2.0% to 6.0%], P = .01; CD54, control subjects: 17.0% [range, 8.0% to 25.0%], NNA: 8.0% [range, 5.3% to 11.5%], NA: 7.0% [range, 4.0% to 15.0%], P = .O;). At 4 AM, CD51 in the distal airways was significantly greater in patients with NA as compared with patients with NNA and control subjects (control subjects, 23.0% [range, 13.8% to 30.5%]; NNA, 32.0% [range, 13.0% to 35.0%]; NA, 40.0% [range, 23.0% to 50.0%], P = .05). Expression of CD51 in the distal airways correlated with the degree of airway obstruction (r = -0.57, P = .001). Control subjects exhibited significant circadian variation in the expression of HLA-DR in the proximal airways and CD54 in the distal airways. CONCLUSION: The increased CD51 at night in patients with NA may be related to increased airway inflammation and repair processes in response to injury. The circadian changes in CD54 and HLA-DR in control subjects require further study to determine their significance. (J Allergy Clin

Adult↗
PubMed1998

Synovial fibroblasts as target cells for staphylococcal enterotoxin-induced T-cell cytotoxicity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology. Recently, superantigens have been implied in the pathogenesis of RA. Superantigens activate a large fraction of T cells leading to the production of cytokines and proliferation. In addition, superantigens direct cellular cytotoxicity towards major histocompatibility complex (MHC) class II-expressing cells. There is now increasing evidence that cytotoxic T cells may be involved in the pathogenesis of RA. In the inflamed synovia class II-positive synovial fibroblasts (SFC) are found. In the present study it was tested whether MHC class II-positive SFC serve as target cells for superantigen-induced cellular cytotoxicity. SFC were stimulated with interferon-gamma to express class II antigens, then they were cultivated in the presence of CD4-positive T cells with or without staphylococcal enterotoxins (SE). Cytotoxicity of T cells was measured as release of lactate dehydrogenase from SFC. Specific cytotoxicity was only found in the presence of class II-positive SFC depending on the dose of SE. Maximum lysis was seen after 20 hr. T-cell cytotoxicity was inhibited by antibodies to MHC class II antigens. The data suggest that class II-positive SFC not only function as accessory cells for SE-mediated T-cell proliferation and interleukin-2 production but may also be the targets of superantigen-mediated cellular cytotoxicity.

Antibodies, Monoclonal↗
PubMed1998

Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma.

Infection with Mycoplasma pneumoniae has been shown to exacerbate asthma in humans. However, the role of M. pneumoniae in the pathogenesis of chronic asthma has not been defined. Eighteen asthmatics with chronic, stable asthma and 11 nonasthmatic control subjects underwent evaluation of the upper and lower airways and serologic analysis to determine the presence of M. pneumoniae, Chlamydia pneumoniae, and seven respiratory viruses through culture, enzyme-linked immunoassay (EIA) and polymerase chain reaction (PCR). M. pneumoniae was detected by PCR in 10 of 18 asthmatics and one of 11 control subjects (p = 0.02). In nine of the 10 patients, the organism was detected in bronchoalveolar lavage or bronchial biopsies. Seven of 18 asthmatics and one of 11 control subjects were also positive for M. fermentans and M. genitalium by PCR. All patients' cultures, EIAs, and serology were negative for M. pneumoniae. All PCR and cultures were negative for C. pneumoniae, and all EIAs for respiratory viruses were negative in all subjects. Nine asthmatics and one control subject exhibited positive serology for C. pneumoniae (p = 0.05). M. pneumoniae was present in the lower airways of chronic, stable asthmatics with greater frequency than control subjects, and may play a role in the pathogenesis of chronic asthma.

Adult↗
PubMed1998

Human corticotropin-releasing hormone improves overnight FEV1 in nocturnal asthma.

Corticotropin-releasing hormone (CRH) exhibits anti-inflammatory properties independent of its effect on adrenal function. We investigated the safety and effect of CRH in nocturnal asthma, a disease where inflammation is prominent. Five subjects underwent an overnight infusion of placebo on the first night, CRH at a 2.5 micrograms/kg/hr on the second night, and three subjects received CRH at 4.0 micrograms/kg/hr on the third night. A significant improvement occurred in overnight change in forced expiratory volume 1 sec. % (delta FEV1) with CRH (+17.4 +/- 9.1%) as opposed to placebo (-25.9 +/- 7.1%), p = 0.024, CRH was well tolerated. Further research with CRH may clarify the pathophysiology of nocturnal asthma.

Adult↗
PubMed1998

Serum cortisol in asthma: marker of nocturnal worsening of symptoms and lung function?

UNLABELLED: Changes in the hormone cortisol have been implicated in the pathogenesis of nocturnal worsening of asthma, or nocturnal asthma (NA). We studied 45 patients, 15 with NA, 15 subjects with non-nocturnal asthma (NNA), and 15 controls over a 24h period, measuring forced expiratory volume in 1 second (FEV1) and serum cortisol at 08:00, 12:00, 16:00, 20:00, 23:00, 04:00, and 08:00 the following day. Evaluation of the time response curves for cortisol revealed a significant difference in the shape of the curves (p = 0.04 by mixed-effects model). Evaluation of individual time points revealed that the cortisol levels in the NNA and control groups were significantly lower than in the NA group at 20:00 (NNA: 3.5 +/- 0.8 mg/mL; CONTROLS: 3.4 +/- 0.8 mg/mL; NA: 4.9 +/- 0.8 mg/mL; p = 0.007). The percentage (%) predicted FEV1 was significantly different among the three groups over the 24h period (p < 0.001). The percentage predicted FEV1 was significantly lower in the NA group compared to the control group at all time points and significantly lower than the NNA group at 16:00, 23:00, and 04:00. The difference among the groups was most pronounced at 04:00, when the percentage predicted FEV1 was 58.9 +/- 2.2% in the NA group, 76.8 +/- 2.9% in the NNA group, and 91.6 +/- 2.8% in the control group (p = 0.001, where each group is significantly different from the others). Although the time response curves for cortisol were significantly different among the three groups, the differences in serum levels of cortisol do not appear to be clinically significant. Therefore, serum levels of cortisol may not be the appropriate measurement to assess the role of cortisol in nocturnal asthma.

Adult↗