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E Taskinen

Publications and source records attributed to E Taskinen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Small airway obliteration in a new swine heterotopic lung and bronchial allograft model.

BACKGROUND: We studied a heterotopic large-animal model with obliterative airway lesions caused by allograft rejection. METHODS: Lung fragments (1 cm3) with airways (LB), and 1 to 2 mm diameter bronchi alone (B) were implanted subcutaneously in 11 domestic piglets weighing 20 kg. Six animals each received 40 implants from nonrelated donors without immunosuppression (group A). Another 5 animals had autograft implants (group U). The implants were harvested consecutively for histologic analysis over 3 months in group A and 6 months in group U. RESULTS: In group U, the initial ischemia caused mild to moderate epithelial damage with moderate metaplasia but with a return to normal ciliary epithelium within 1 month. Transient mild luminal obliteration with granulation tissue and mononuclear cells was observed during the first weeks, but after 4 weeks the lumen was patent and filled with mucus. In the bronchial wall, moderate fibrosis developed in LB implants, whereas mild fibrosis was seen in B implants. In group A, the epithelium was totally absent by 2 weeks, and mild inflammation, fibrosis, and destruction of the cartilage with pericartilaginous mononuclear accumulation were observed in the bronchial wall. Small airways were gradually obliterated between days 7 and 21, initially by granulation tissue and mononuclear cells and later by progressive fibrosis. CONCLUSIONS: In this model, autografted airway implants stayed patent for at least 6 months, whereas total luminal obliteration histologically resembling obliterative bronchiolitis developed in allografts within 21 days. Because small airways, including bronchioli, can be transplanted with the use of this model, it may be useful for research into the causes of airway obliteration, which may be relevant to the pathogenesis of obliterative bronchiolitis in lung recipients.

Animals↗
PubMed1997

A rat model of monitoring liver allograft rejection.

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 +/- 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 +/- 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 +/- 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1% +/- 2% to 21% +/- 13%) and class II (from 20% +/- 9% to 43% +/- 13%) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection.

Animals↗
PubMed1997

Persistent cytomegalovirus in liver allografts with chronic rejection.

Cytomegalovirus (CMV) infection is one of the suggested risk factors for chronic allograft rejection. Clinical and experimental studies have shown that CMV is somehow implicated in rejection mechanisms and in the generation of graft arteriosclerosis, characteristic of chronic rejection. In liver transplantation, there is also evidence of an association between CMV and vanishing bile duct-syndrome (VBDS), which is characteristic of chronic liver allograft rejection. In this study, the role of posttransplant CMV infection and of acute rejection in the patients with irreversible, histologically confirmed chronic liver rejection with VBDS and vasculopathy was analyzed. Ten of 200 (5%) consecutive liver transplants were lost due to chronic rejection, from between 5 and 28 months from transplantation. In these 10 patients, acute rejections were frequent, and nine of ten patients had at least one episode of rejection early after transplantation. All patients (10 of 10) had a history of CMV infection usually following acute rejection. To investigate the role of CMV in chronic rejection, nine available removed grafts were examined for the presence of the CMV genome by DNA-hybridization in situ using a biotinylated CMV-DNA probe. Persistent CMV-DNA was found in all of those available grafts with chronic rejection. CMV-DNA was strongly expressed in the remaining bile ducts and moderately expressed in the endothelial cells of the vascular structures, the CMV positivity of hepatocytes varied from graft to graft. Thus, persistent CMV genome was found in those structures that are the major targets of the chronic rejection process in the liver. These findings support the previous suggestion of an association between CMV and chronic allograft rejection.

Bile Ducts↗
PubMed1997

Experimental piglet lung transplantation: histological bioptic changes and autopsy findings.

To investigate difficulties in diagnosing pulmonary rejection and to create a new model to observe long-term histological consequences, 21 piglets were subjected to left single lung transplantation. Five of these transplants served as targets for unmodified rejection in piglets without immunosuppression (Group I), 13 recipients were treated with cyclosporin A, azathioprine and methylprednisolone (Group II), and in 3 cases reimplantation of an autograft was performed (Group III). In the course of postoperative graft monitoring, transthoracic/bronchial biopsies were obtained on days 3, 5, 7, 10, 14, and 20, and thereafter less frequently up to 134 days. In the unmodified rejection group, grafts consolidated in one week and histologically presented perivascular mononuclear cell infiltrates, except for one case which showed vasculitis. Lymphocytic bronchiolitis and or peribronchiolar infiltrate was present in three of the four autopsied grafts. In Group II acute rejection was detected six times in three piglets, and all except one of these specimens had a peribronchiolar component. Although no incontestable bronchiolitis obliterans developed, mild to moderate chronic obliterative vascular lesions were detected in all immunosuppressed piglets (n = 3) surviving more than 80 days. Contralateral lungs and Group III autografts showed mild changes related to the operation itself and interstitial swine endemic pneumonia (SEP). Chronic changes related to rejection were limited to the vascular wall. The mainly inflammatory bronchiolar changes are thought to present an incipient phase leading to obliterative lesions.

Anastomosis, Surgical↗
PubMed1997

Detection of acute rejection by 133Xe radiospirometry after single lung transplantation in an experimental porcine model.

Aim of this experimental study was to evaluate acute rejection in a porcine single-lung transplantation model by using 133Xe radiospirometry. Left lung allotransplantation was performed on 11 and autotransplantation on 5 piglets. Postoperative monitoring consisted of 77 radiospirometric examinations with assessments of regional perfusion (Qtx), ventilation (V) and ventilation/perfusion ratio (V/Qtx). Results were compared with transbronchial biopsy. A significant decrease in Qtx (p < 0.01) and an increase in V/Qtx (p < 0.01) were observed during acute rejection, whereas V remained unaltered. These changes were significant already at minimal rejection (grade A1), and further increased at moderate rejection (grade A3). Sensitivity and specificity of Qtx were 82 and 74%, and those of V/Qtx, 87 and 65%. 133Xe radiospirometry detects even minimal acute rejection after single lung transplantation.

Acute Disease↗
PubMed1997

High-resolution CT in long-term follow-up after lung transplantation.

OBJECTIVE: Our aim was to evaluate the development of changes on high-resolution CT (HRCT) associated with chronic pulmonary rejection. MATERIALS AND METHODS: Repeated HRCT examinations were performed 140 times on 13 consecutive lung transplant recipients during a mean observation period of 26 months. The postoperative time interval to the first detection of each chronic change on CT was calculated and compared with the onset of chronic rejection. Bronchiolitis obliterans syndrome (BOS) or the histologic diagnosis of obliterative bronchiolitis was assessed by the published criteria of the International Society for Heart and Lung Transplantation. RESULTS: BOS developed in eight patients, on an average, within 11.6 (+/-5.0) months. Histologic diagnosis was available from five patients. On HRCT, among the first identifiable chronic changes were volume contraction, decreased peripheral vascular and bronchial markings, and thickening of septal lines, all of which appeared between 7 (+/-5.0) and 11 (+/-6.8) months postoperatively. The mean interval for appearance of bronchodilatation was 12.5 (+/-8.7) months. Hyperlucency and mosaic phenomenon were identified, on an average, 16 (+/-6.3) and 21 (+/-7.3) months after transplantation. CONCLUSION: On radiologic monitoring of lung recipients with HRCT, in addition to bronchodilatation. a special attention should be paid to the early chronic changes, including diminution of peripheral bronchovascular markings, thickening of septal lines, and volume reduction, which usually precede the establishment of the diagnosis of chronic rejection, whereas hyperlucency and mosaic phenomenon usually appear during more advanced BOS.

Bronchiolitis Obliterans↗
PubMed1997

Acute rejection diagnosed with computed tomography in a porcine experimental lung transplantation model.

The role of computed tomography (CT) in the diagnosis of acute rejection was studied in an experimental lung transplantation model, with 15 left lung allotransplantations and six autotransplantations performed on piglets weighing 16-24 kg. There were 31 episodes of acute rejection. In the allotransplantation group the development of acute rejection was monitored 115 times with CT, transbronchial biopsy (TBB) and bronchoalveolar lavage (BAL). The stages of acute rejection were 1) ill-defined centrilobular micronodules or minimal patchy ground-glass opacities. 2) dense, small-nodular infiltration or extensive ground-glass opacities, and bronchial wall thickening. 3) lung volume loss and dense, patchy ground-glass opacities and 4) consolidation of the lung. In the autotransplantation group monitoring was done 42 times. After allotransplantation, TBB and BAL suggested rejection 60 times and infection 23 times. CT had 86.7% sensitivity and 85.6% specificity. During the first month these figures were, respectively, 71.4% and 84.2%. Rising histologic grade was associated with increasing stage of acute rejection on CT, which thus proved to be a sensitive and specific method for diagnosing acute rejection of lung transplant.

Acute Disease↗
PubMed1996

Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance.

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

Age Factors↗
PubMed1996

Expression of adhesion molecules and their ligands in liver allografts during cytomegalovirus (CMV) infection and acute rejection.

Vascular adhesion molecules and their ligands are important in leukocyte-endothelial cell interactions and in T-cell activation of rejection cascade. Also, cytomegalovirus (CMV) infection is suggested to be involved in the mechanisms of rejection. In this study, the expression of vascular adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in the liver allografts, the number of leukocytes positive for their ligands LFA-1, VLA-4 and SLex, and activation markers (class II, IL2-receptor) were investigated in liver allografts during CMV infection and acute rejection and compared to grafts with normal function and histology. The adhesion molecules, their ligands and activation markers were demonstrated from liver biopsy frozen sections by the immunoperoxidase technique and monoclonal antibodies. A significant induction of ICAM-1 and VCAM-1 was seen in vascular and sinusoidal endothelium associated with both CMV and rejection, and induction of ELAM-1 in vascular endothelium in rejection only. In both cases, the number of leukocytes expressing LFA-1 was significantly increased, but VLA-4-positive cells were more characteristic for CMV and SLex-positive cells more for rejection. IL2-receptor positivity was practically seen in rejection only, but class II-expressing cells were increased during both CMV infection and rejection. In conclusion, adhesion molecules were induced and the infiltrating cells expressed their ligands both in liver rejection and during CMV infection, although the expression pattern was slightly different.

Acute Disease↗
PubMed1996

Assessment of Reproductive Risk at Work.

The risk-assessment process involves hazard identification, dose&endash;response assessment, exposure assessment, and characterization of risk. Special competence and careful consideration are needed to assess effects on human reproduction. There is often a lack of scientific information concerning, e.g., toxic influences of chemical substances on human fertility, pregnancy, and offspring. Legislation and guidelines concerning workplace exposures need further development in many countries. It is important that occupational health and safety personnel, as well as experts in this field, assist employers and employees in the development of good workplace policies for the protection of the reproductive functioning of male and female workers. A protocol for effective risk assessment is described.

Journal Article↗
PubMed1996

Endothelin in bronchoalveolar lavage fluid is increased in lung-transplanted patients.

Animal studies have shown increased endothelin in bronchoalveolar lavage (BAL) fluid during unmodified rejection. We performed radioimmunoassay of endothelin in 59 BAL fluid samples from ten patients at different times after lung transplantation. All patients received immunosuppressive therapy (cyclosporin, azathioprine and methylprednisolone). Reference BAL samples were obtained from six controls. Of the 59 test samples, five were collected during rejection episodes, confirmed by clinical outcome, BAL cytology and radiology (rejection group), and 19 were taken during bacterial, viral or fungal infection (infection group). The endothelin content of BAL (pg/ml) was significantly greater in the rejection group than in the infection group (61.1 +/- 3.8 vs 40.6 +/- 2.0) or in the 35 samples taken in uncomplicated course after lung transplantation (40.9 +/- 5.4), p < 0.01. The endothelin level in BAL fluid from the controls was only 3.0 +/- 1.4 pg/ml, significantly less (p < 0.005) than in all the lung-transplanted groups. Endothelin in BAL fluid thus was increased after lung transplantation, and still further during rejection.

Bronchoalveolar Lavage Fluid↗