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M Tamm

Publications and source records attributed to M Tamm.

At least 37 records · Page 2Linked to original sources
PubMed2004

Advances in bronchoscopy--therapeutic bronchoscopy.

The common indications for therapeutic bronchoscopy include relief of benign and malignant airway stenosis, in the intensive care unit, foreign body removal and management of hemoptysis. Debulking of airway tumors may be undertaken using techniques such as laser photoresection, electrocautery, cryotherapy, argon plasma coagulation or mechanically using rigid bronchoscopy. These techniques are often used in combination. Balloon dilatation and insertion of silicone or metallic airway stents can be undertaken to treat benign and malignant strictures or bronchomalacia. Airway stents maintain luminal patency by opposing extrinsic compressive forces or by providing internal support. Certain stent types may also physically prevent (Silicone and covered metallic stents) the encroachment of tumor tissue into the airways. Covered metallic airway stents are safe and effective in the management of malignant tracheoesophageal fistulae, reduce the risk of recurrent aspiration and provide enhanced quality of life by allowing resumption of oral nutrition. In this article, we present an overview of application and the current methods available to perform therapeutic bronchoscopy.

Airway Obstruction↗
PubMed2003

[Lung embolism in the elderly].

Elderly people have an increased risk of suffering from thrombo-embolic events. Lung embolism is often found as a cause of death in autopsies in elderly people. However, it is unknown whether the increased age is a risk factor per se or whether elderly people suffer more often from co-morbidities associated with a higher thrombo-embolic risk. Immobility is the most important risk factor for thrombo-embolic events. Other risk factors include trauma, surgery, venous stase, genetic factors (thrombophilia) and a history of past thrombo-embolic events. Although the probability of suffering from a thrombo-embolic event increases with age, it can be difficult to find the correct diagnosis in elderly people: symptoms like dyspnoe or chest pain might be explained by other cardio-pulmonary diseases. In this review, we would like to give an overview about the diagnostic and therapeutic steps in elderly people.

Aged↗
PubMed2003

Short- and long-term outcome after lung resection for invasive pulmonary aspergillosis.

BACKGROUND: Lung resection for invasive pulmonary aspergillosis (IPA) is controversial. Neutropenia, thrombopenia and poor general condition may increase perioperative morbidity and mortality, and the redeeming benefit is questionable. Therefore we analyzed short- and long-term outcome after lung resection for IPA. METHODS: 41 patients with hematological disease underwent lung resection for suspected IPA: lobectomy (23 patients), wedge-resection (16) and enucleation (2). RESULTS: 4 (10%) patients developed major complications: pleural aspergillosis, bronchial stump insufficiency, severe bleeding, ARDS. 11 (27%) patients showed minor complications: pleural effusion (6), pneumothorax (2), seroma (2) and hematothorax (1). 30-day mortality was 10 % (4 of 41 patients): two died of bacterial septicemia, two of disseminated aspergillosis. One (2%) death was possibly surgery-related. IPA was cleared in 87% of patients, fungal relapse occurred in 4 (10%) patients. Overall survival was 65%, 58% and 40% at 6 months, 12 months and 5 years. CONCLUSION: Lung resection for IPA even in profound cytopenia is feasible with acceptable morbidity and mortality. Fungal infection can be cured in more than 80 % of patients. Long-term outcome can be achieved if the hematological disease is under control.

Adolescent↗
PubMed2002

Photo-induced oxidation of a dinuclear Mn(2)(II,II) complex to the Mn(2)(III,IV) state by inter- and intramolecular electron transfer to Ru(III)tris-bipyridine.

To model the structural and functional parts of the water oxidizing complex in Photosystem II, a dimeric manganese(II,II) complex (1) was linked to a ruthenium(II)tris-bipyridine (Ru(II)(bpy)(3)) complex via a substituted L-tyrosine, to form the trinuclear complex 2 [J. Inorg. Biochem. 78 (2000) 15]. Flash photolysis of 1 and Ru(II)(bpy)(3) in aqueous solution, in the presence of an electron acceptor, resulted in the stepwise extraction of three electrons by Ru(III)(bpy)(3) from the Mn(2)(II,II) dimer, which then attained the Mn(2)(III,IV) oxidation state. In a similar experiment with compound 2, the dinuclear Mn complex reduced the photo-oxidized Ru moiety via intramolecular electron transfer on each photochemical event. From EPR it was seen that 2 also reached the Mn(2)(III,IV) state. Our data indicate that oxidation from the Mn(2)(II,II) state proceeds stepwise via intermediate formation of Mn(2)(II,III) and Mn(2)(III,III). In the presence of water, cyclic voltammetry showed an additional anodic peak beyond Mn(2)(II,III/III,III) oxidation which was significantly lower than in neat acetonitrile. Assuming that this peak is due to oxidation to Mn(2)(III,IV), this suggests that water is essential for the formation of the Mn(2)(III,IV) oxidation state. Compound 2 is a structural mimic of the water oxidizing complex, in that it links a Mn complex via a tyrosine to a highly oxidizing photosensitizer. Complex 2 also mimics mechanistic aspects of Photosystem II, in that the electron transfer to the photosensitizer is fast and results in several electron extractions from the Mn moiety.

2,2'-Dipyridyl↗
PubMed2002

[N-acetylcystein in the therapy of chronic bronchitis].

Chronic bronchitis (CB) shows an increasing global morbidity and mortality with major impact on socioeconomics. N-Acetylcysteine (NAC), previously used as a mucolytic compound in CB, has also antioxidative effects. Furthermore it influences intrabronchial bacterial colonisation. In a randomised pilot study of 24 patients (16-male, 8 female, mean age 66 +/- 10 years) with acute exacerbation of CB and positive bacterial culture in the sputum, the addition of twice daily 600 mg NAC to standard antibiotic therapy lead to a significantly higher bacterial eradication rate (70 % versus 36 %, p < 0.03). Clinical studies suggest that treatment with NAC has different effects in CB including a reduction of the number and duration of acute exacerbation episodes and possibly influences lung function. The improvement of symptoms and quality of life also has an impact on socio-economic costs. The use of NAC in CB as an antioxidative rather than a mucolytic compound should be considered. However, further placebo controlled studies are undergoing to definitively establish the role of NAC for the treatment of CB and COPD.

Acetylcysteine↗
PubMed2002

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients.

Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in neutropenic patients. Microbiological and serological tests are of limited value. The diagnosis should be considered in neutropenic patients with fever not responding to antibiotics, and typical findings on thoracic computed tomography scan. Whenever possible, diagnosis should be confirmed by tissue examination. Newer techniques, such as polymerase chain reaction may change the current diagnostic approach. Therapeutic strategies consist of prophylaxis in risk groups and the early application of antifungal agents in suspected or probable disease. Amphotericin B as desoxycholate or lipid formulation is the current standard medication in invasive infection, although it has major side effects. Its role is challenged by the new azole derivates, such as itraconazole and voriconazole, and the new echinocandins. Additional therapies with cytokines, such as granulocyte macrophage colony stimulating factor and interferon-gamma, and with granulocyte transfusions are under evaluation. In selected cases lung resection is of proven diagnostic and therapeutic value. This paper analyses the current understanding of the pathogenesis and epidemiology of invasive aspergillosis and reviews the actual diagnostic and therapeutic strategies for invasive pulmonary aspergillosis in neutropenic patients.

Amphotericin B↗
PubMed2001

Functional genomics in sarcoidosis--reduced or increased apoptosis?

BACKGROUND: A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signaling pathways. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in patients with acute onset sarcoidosis. METHOD: We have performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HGU95A, Affymetrix) for RNA expression profiling from peripheral blood mononuclear cells from patients with acute pulmonary sarcoidosis and matched healthy controls. Twelve patients and 12 controls were assessed, mean age 36 +/- 12 and 33 +/- 10 years respectively. Results focus on apoptosis-related gene products. Group differences were assessed with the Mann-Whitney U-test. RESULTS: Seven patients had self-limited disease (all type I sarcoidosis) and 5 progressive disease requiring immunosuppression (all type II or III sarcoidosis). We found 53 of 112 (47%) apoptosis-related gene products dysregulated in sarcoidosis compared to controls. Particular growth factors, especially heparin-binding EGF-like GF, EGF, PDEGF, SISPDGF2 and VEGF, were upregulated in patients consistent with a pro-survival profile. The Bcl-2 family of genes also showed a net pro-survival profile in sarcoidosis patients. In contrast, alterations in the TNF-pathway were compatible with increased apoptosis signals in both, type I and type II/III sarcoidosis patients. Other cell death receptors were equally expressed, as were caspases and p53-associated genes. In contrast to patients with type I-sarcoidosis, patients with progressive type II or III disease showed an upregulation of NFKB and a leak of downregulation of inhibitor of apoptosis 1. CONCLUSION: Significant differences in the expression of apoptosis-related genes were found in peripheral blood of patients with acute onset sarcoidosis. Gene expression did not show a definite pattern that was suggestive of pro-survival or proapoptosis. However, the number of genes whose altered expression would be predicted to favour increased survival exceeded that of genes likely to reduce survival. Protein-based confirmation of the differences in the activity of apoptosis-pathways needs to be done in further studies.

Acute Disease↗
PubMed2001

Airway smooth muscle cell proliferation is increased in asthma.

UNLABELLED: Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be the result of increased muscle proliferation. We have for the first time been able to culture ASM cells from asthmatic patients and to compare their proliferation rate with that of nonasthmatic patients. Asthmatic ASM cell cultures (n = 12) were established from explanted lungs and endobronchial biopsies. Nonasthmatic ASM cells (n = 10) were obtained from explanted tissue from patients with no airway disease, emphysema, carcinoma, and fibrosing alveolitis. Cell counts, tritiated thymidine incorporation, and cell cycle analysis were conducted over 7 d. Asthmatic ASM cell numbers at Days 3, 5, and 7 were significantly higher than corresponding values for nonasthmatic cells (p < 0.05). Tritiated thymidine incorporation was increased 3.2-fold in asthmatic cells compared with nonasthmatic cells within the first 24 h (p = 0.026). Flow cytometric analysis of DNA content on Days 1 and 2 revealed that a significantly greater percentage of asthmatic ASM cells were in the G2 + M phase (p < 0.05). This study shows for the first time that proliferation of ASM cells is increased in patients with asthma and provides evidence for an intrinsic abnormality in the ASM cell in this disease. KEYWORDS: asthma; human airway smooth muscle; cell culture; cell proliferation; hyperplasia

Adolescent↗
PubMed2001

Diagnostic value of follow-up transbronchial lung biopsy after lung rejection.

Although transbronchial lung biopsy (TBBx) is widely acknowledged as the "gold standard" for diagnosis of acute rejection, controversy exists regarding the need to perform follow-up procedures. Over a 5-yr period, we performed 1,142 TBBx of which 173 were follow-up TBBx in 99 patients with pulmonary allograft rejection greater than or equal to International Society for Heart and Lung Transplantation (ISHLT) grade A(2) on initial TBBx. Rejection on the previous 173 TBBx was associated with lymphocytic bronchiolitis/bronchitis (LBB) > or = ISHLT grade B(2) in 82 patients and with cytomegalovirus (CMV) pneumonitis in 16 patients. Persistent rejection (> or = A(2)) was observed in 45 of 173 (26%) follow-up TBBx. Persistent B grade rejection (> or = B(2)) was present in 28 patients whereas new B grade rejection developed in 11 patients with > or = A(2) grade rejection. Rejection > or = B(2) was significantly (p < 0.05) associated with rejection > or = A(2). Fifteen follow-up TBBx showed new B grade rejection without signs of > or = A(2) rejection. A new diagnosis of CMV pneumonitis was made in 33 of 173 (19%). CMV pneumonitis occurred in 35 follow-up TBBx, four associated with > or = A(2) rejection and eight with > or = B(2) rejection. The overall incidence of bronchiolitis obliterans syndrome (BOS) in both groups was similar. Patients with persistent rejection on follow-up TBBx developed BOS at a median of 1.3 yr and median of 2.0 yr (p = not significant [NS]) posttransplantation. The practice of follow-up TBBx after rejection within 2 yr posttransplant is clinically useful as it provides valuable diagnostic information.

Adolescent↗
PubMed2001

Distinct endobronchial expression of matrix-metalloproteinases (MMP) and their endogenous inhibitors in lung cancer.

BACKGROUND: Degradation of extracellular matrix (ECM) and basement membranes is required for tumour cell invasion and metastasis. The ECM is degraded by matrix metalloproteinases (MMP) which are counteracted by tissue inhibitors of metalloproteinases (TIMP). In aggressive tumours the balance of proteolysis and antiproteolysis is disrupted, resulting in fast tumour progression and invasiveness. We examined MMP and TIMP expression patterns in bronchial washings of 58 consecutive lung tumour patients and 10 controls. Pathohistological investigations revealed squamous cell carcinoma (n = 23), adenocarcinoma (n = 18), small cell lung carcinoma (n = 9), and pulmonary metastases of extrapulmonary tumours (n = 8). MMP/TIMP expression was correlated to histology, location, or staging of tumours. METHODS: Expression and activity of MMP was identified by zymography and Western blotting. Expression of TIMP-1 and TIMP-2 was analysed by Western blotting and enzyme-linked immunosorbent assays. RESULTS: We identified MMP-1, MMP-2 and MMP-9, but not MMP-3 or MMP-8 in bronchial washings. All MMPs were expressed in the tumour-affected and the tumour-free parts of the lung. While MMP-1 and MMP-9 were present in all samples, the inactive precursor of MMP-2 was specifically expressed in adenocarcinoma or lung metastases of extrapulmonary tumours. No MMP-2 was found in controls. While TIMP-1 was expressed in all samples, TIMP-2 was not detectable. CONCLUSION: The tumour type-specific expression of the MMP-2 precursor in adenocarcinoma and lung metastases suggests that MMP-2 in the absence of TIMP-2 correlates with aggressive tumour progression and may serve as an indicator for poor prognosis.

Adenocarcinoma↗
PubMed2001

Cytomegalovirus infection and graft rejection in renal transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection and CMV disease have been associated with acute and chronic graft rejection. The introduction of the sensitive CMV antigenemia pp65 assay for detection of CMV infection allowed us to study the time course of CMV infection and acute rejection and the long-term outcome in renal transplant recipients with and without a CMV risk constellation. METHODS: Prospective single center study including 48 renal transplant recipients at risk for CMV infection (donor and/or recipient CMV seropositive) and a control group of 36 CMV seronegative recipients of CMV seronegative kidney donors. Evidence of CMV infection was monitored by the CMV antigenemia pp65 assay every 1 to 2 weeks and compared with the occurrence of acute rejection in the posttransplant period and graft function at 5 years. RESULTS: CMV infection developed in 83% (40/48) of patients of the CMV risk group within 4 months posttransplant. A total of 18 of patients experienced an acute rejection episode (control group 16/36; P=0.65). In 12/18 CMV infection followed rejection and in three patients antigenemia preceded the diagnosis of rejection. In three patients CMV antigenemia remained negative. Five-year follow up: Patient survival (44/48 vs. 31/36; P=0.48), graft survival (38/48 vs. 27/36; P=0.79), number of patients with at least one acute rejection episode: CMV risk group: 42.1%, control group 51% (P=0.46), serum creatinine: CMV risk group:130 +/- 66 micromol/iter, control group: 126 +/- 37 micromol/ liter (P=0.56), proteinuria: CMV risk group: 0.02 +/- 0.02 g/mmol creatinine, control group: 0.02 +/- 0.02 g/mmol creatinine (P=1.0). CONCLUSION: CMV infection within 4 months posttransplant, as defined by a positive antigenemia assay was not found to be a risk factor for acute graft rejection or chronic graft dysfunction at 5 years.

Adult↗
PubMed2001

Primary fibroblast cell cultures from transbronchial biopsies of lung transplant recipients.

BACKGROUND: Survival after lung transplantation is limited by the development of bronchiolitis obliterans (BO) that is a fibroproliferative process and regarded as the histological marker of chronic rejection. To study further the pathogenesis of BO we attempted to establish primary fibroblast cell cultures from transbronchial lung biopsies (TBBs)of lung transplant recipients. METHODS: One to two TBB samples from each patient were collected in sterile phosphate-buffered saline. Biopsies were cut into small pieces and placed onto 25-cm2 culture flasks for cell culture and kept under standard cell culture conditions (21% O2, 5% CO2, 37 degrees C). Culture medium consisted of RPMI 1640, 10% fetal calf serum, L-glutamine, HEPES, and antibiotics. After reaching confluence, fibroblasts were passaged into 75-cm2 flasks. RESULTS: The success rate of establishing fibroblast cultures from transbronchial lung biopsies was 54% (27/50). Cell growth was independent of patient age, transplant type, underlying lung disease, indication for transbronchial lung biopsies, grade, or type of re jection and infection. CONCLUSIONS: We have established a novel method of culturing fibroblasts from lung transplant recipients. We consider this method as an unique human in vitro model to study the pathogenetic mechanisms leading to BO.

Adult↗
PubMed2001

Diagnostic yield of bronchoalveolar lavage following renal transplantation.

Organ transplant recipients are at high risk of infectious pulmonary complications. In this retrospective study, the diagnostic yield of bronchoalveolar lavage (BAL) was evaluated in renal transplant recipients. The results were analysed in special regard to the clinical presentation of pulmonary infections and the possible impact of new immunosuppressive agents. Over a 5-year period 91 BAL were performed in 71 renal transplant recipients. Microorganisms were isolated from 69% of BAL (63/91): bacteria 32%; cytomegalovirus (CMV) 27%; Pneumocystis carinii (PC) 22%; other viruses 9% (HSV; EBV, RSV, adenovirus, HHV8); Aspergillus fumigatus 1%. Total cell counts and neutrophil counts in BAL were significantly elevated in bacterial infection, whereas BAL positive for PC showed eosinophilia (P<0.05). There was no association between clinical symptoms and the radiological pattern of infiltrates and the type of infection. Immunosuppression containing tacrolimus or mycophenolate mofetil was associated with a significantly higher percentage of PC and CMV infections compared to cyclosporin-based immunosuppression (65% vs. 30%, P<0.005). A considerable number of PC and CMV infections occurred beyond 6 months after transplantation. In conclusion, BAL has a high diagnostic yield in renal transplant recipients. Infection with CMV and PC should also be considered beyond 6 months after transplantation, and prophylaxis for opportunistic infections should be given if the immunosuppression is intensified.

Adult↗
PubMed2001

Pulmonary scedosporium infection following lung transplantation.

Infectious complications are frequent following lung transplantation. Tracheobronchial aspergillosis is the predominant fungal infection in these patients. Infections with Scedosporium apiospermium (Pseudoallescheria boydii) and Scedosporium prolificans (Scedosporium inflatum) have mainly been described in bone marrow transplant recipients and only occasionally in solid organ transplant recipients. We analysed risk factors, the clinical course and outcome of seven lung transplant recipients who developed pulmonary scedosporium infection. Scedosporium apiospermium was documented in bronchoalveolar lavage (BAL) of all seven and Scedosporium prolificans in the BAL of four of these patients. Scedosporium was detected 9-58 months after transplantation. Five of the seven patients had been treated for several months with itraconazole because of previous detection of aspergillus in BAL. All seven patients with scedosporium infection showed airway problems, including early ischemic airway stenosis in one and bronchiolitis obliterans syndrome in the other six patients. Combined treatment with itraconazole and fluconazole was not able to eradicate scedosporium. Four of the seven patients died with advanced bronchiolitis obliterans 3-35 months after the diagnosis of pulmonary scedosporium infection. Three patients are currently alive 3, 6 and 7 years after transplantation, showing persistent scedosporium infection. In conclusion, pulmonary scedosporium infection was seen in lung transplant recipients with structurally abnormal airways and under long-term therapy with itraconazole. Eradication of scedosporium proved difficult, but under combined treatment with itraconazole and fluconazole this opportunistic infection did not disseminate.

Adult↗
PubMed2001

Invasive pulmonary fungal infection in hematologic patients: is resection effective?

INTRODUCTION: Invasive pulmonary aspergillosis carries a high mortality in neutropenic patients. Descriptive reports have shown early surgery to be feasible with acceptably low morbidity. The possible benefit of surgery has not been investigated in comparative studies. MATERIALS AND METHODS: In a retrospective cohort study encompassing a 15-year period, 54 (8%) of 697 consecutive patients with severe hematological disease required treatment for localized invasive pulmonary aspergillosis. Patients treated by antifungal drugs (medical group, n = 24) were compared to patients treated with additional early lung resection (surgical group, n = 30). Outcomes analysed were fungal progression and survival. RESULTS: Fungal progression at six months was 17% (95% CI 3-31) in the surgical group and 52% (95% CI 34-73) in the medical group (P = 0.005). Survival at six months was 70% (95% CI 53-87) in surgically and 42% (95% CI 24-62) in medically treated patients (P = 0.009). Adjusting for differences in WHO performance score (worse in the medical group) and duration of neutropenia (longer in the surgical group) in a multivariate analysis, a difference in relative risk of death (0.26; 95% CI 0.08-0.88; P = 0.03) remained in favor of surgery. CONCLUSION: In this retrospective study surgical intervention to treat invasive pulmonary fungal disease appeared to have a beneficial effect on the impact of disease control and survival. Differences in baseline characteristics of the two patient groups calls for cautious interpretation. A prospective randomized trial seems warranted.

Adolescent↗
PubMed2001

'If I had a friend in a wheelchair': children's thoughts on disabilities.

The purpose of the present study was to examine what notions there are among ordinary preschool children and schoolchildren about physically handicapped children using wheelchairs. Forty-eight children-16 children of preschool age (half boys, half girls, aged around 6), 16 children in primary school class 2 (half boys, half girls, aged around 8) and 16 children in class 4 (half boys, half girls, aged around 8)-constituted the investigated group. The method used was a combination of drawings produced by the children themselves serving as a projective image, interview questions in connection with the drawings and a self-assessment scale, based on Osgood's semantic differential technique. The results showed that most children had favourable attitudes towards a child in a wheelchair. They were willing to include the disabled child in their games and recreational activities, and they considered that the disabled child would have many friends and a high self-esteem. However, they saw real obstacles for the disabled child both in play situations and in other environmental settings. No tangible differences between the sexes could be found; however, differences by age were present. The results were discussed with regard to earlier research and topics for further research are suggested.

Attitude↗
PubMed2001

Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblasts.

Lung fibrosis is a fatal condition of excess extracellular matrix (ECM) deposition associated with increased transforming growth factor beta (TGF-beta) activity. Although much is known about its pathological features, our understanding of the signal transduction pathways resulting in increased ECM and collagen deposition in response to TGF-beta is still incompletely defined. We have previously reported that a JunD homodimer of the transcription factor AP-1 is specifically activated by TGF-beta in lung fibroblasts. Here we demonstrate that JunD is also specifically required for TGF-beta-induced effects. Antisense against JunD, but not c-fos or c-jun, significantly inhibited collagen deposition in response to TGF-beta in primary human lung fibroblasts. We then investigated the ability of pharmacological agents to inhibit TGF-beta-induced signaling and collagen deposition. Cs-A and IFN-gamma, but not glucocorticoids, cyclophosphamide, or azathioprine, inhibited TGF-beta-induced signaling, as assessed by luciferase reporter gene assays, and collagen deposition. TGF-beta antagonism by Cs-A was associated with direct inhibition of JunD activation, as demonstrated by electrophoretic mobility shift analyses. In contrast, the effects of IFN-gamma required signal transducer and activator of transcription (STAT)-1. We thus identify the JunD isoform of AP-1 as an essential mediator of TGF-beta-induced effects in lung fibroblasts. TGF-beta-induced signaling and collagen deposition are efficiently antagonized by Cs-A and IFN-gamma treatment, both of which exhibit distinct molecular mechanisms of action. These observations therefore offer novel targets for future therapy of fibrotic lung disease.

Cells, Cultured↗