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Biomedical subjects

A Pforte

Publications and source records attributed to A Pforte.

At least 19 recordsLinked to original sources
PubMed2004

Epidemiology, diagnosis, and therapy of pulmonary embolism.

Pulmonary embolism is a frequently observed clinical symptom. Its mortality rate is ca. 10 % und occurs mainly in the acute phasis. Immobilization, surgery, old age, malignancies, hormonal factors as well as inherited or acquired thrombophilia are important risk factors. Spiral computed tomography and ventilation-perfusion-scintigraphy are the decisive imaging methods. Pulmonary angiography is still the gold standard. The risk of pulmonary embolism could be lowered by 50 % through prophylaxis with unfractioned or low-molecular-weight heparin. The therapy of pulmonary embolism stratifies the clinical grade and reaches from ambulant therapy with low-molecular-weight heparin to thrombolysis or embolectomy in massive pulmonary embolism. Long-term anticoagulation, usually with vitamin-K-antagonists, should be applied according to the individual risk profile of the patient.

Angiography↗
PubMed2003

Interleukin-18 expression in BAL cells of sarcoidosis patients is decreased in vivo but protein secretion is not impaired in vitro.

Recently, increased expression of interleukin-18 (IL-18) has been shown in sarcoid airway epithelium. However, IL-18 expression has not been investigated extensively in bronchoalveolar lavage (BAL) cells in sarcoidosis yet. Expression of IL-18 and tumour necrosis factor-alpha (TNFalpha) mRNA in cells of the BAL of 23 patients with sarcoidosis and nine healthy volunteers was determined using semiquantitative RT-PCR. IL-18 protein in BAL cells was investigated by immunocytochemistry (ICC). IL-18 protein levels in BAL cell culture supernatants from patients and controls with and without LPS stimulation were measured by enzyme-linked immuno-sorbent assay. BAL cells from patients were stimulated with either IL-10 or IL-13 and IL-18 protein levels were determined. IL-18 mRNA expression was significantly decreased in BAL cells of patients compared to control subjects (1.62 +/- 0.27 vs. 4.29 +/- 0.77, P < 0.05). TNFalpha mRNA expression was significantly increased in BAL cells of patients in comparison to control subjects (0.63 +/- 0.09 vs. 0.11 +/- 0.08, P < 0.05). ICC showed less positive alveolar macrophages in sarcoidosis patients than in control subjects (26 vs. 53%). IL-18 protein levels did not differ significantly between both groups. Stimulation with IL-10 significantly reduced IL-18 protein concentration in sarcoidosis patients. Our results suggest that BAL cells may not be the main source of IL-18 production in sarcoidosis in vivo. Since IL-18 production of BAL cells was not impaired in culture antiinflammatory cytokines might contribute to decreased IL-18 expression in vivo.

Adult↗
PubMed2003

Increased interleukin-13 expression in patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disorder of unknown origin. Lymphocytic inflammation is dominated by expression of Th1 type cytokines such as tumour necrosis factor alpha (TNFalpha). Interleukin 13 (IL-13) is a Th2 cytokine which is expressed by CD4+ T cells and has been shown to suppress TNFalpha in human blood monocytes. The role of IL-13 as a possible anti-inflammatory cytokine in sarcoidosis was investigated. METHODS: mRNA expression of IL-13, IL-4, IL-10, and TNFalpha in bronchoalveolar lavage (BAL) fluid cells and peripheral mononuclear blood cells (PBM) of 18 patients with sarcoidosis and nine healthy controls was assessed using RT-PCR. In addition, IL-13 protein levels in BAL cell culture supernatants from 12 patients and all controls were measured and immunocytochemistry of IL-13 protein was performed in BAL fluid cells of eight patients. TNFalpha concentrations were measured with and without stimulation with recombinant human (rh) IL-13, rhIL-10, and lipopolysaccharide (LPS). RESULTS: IL-13 mRNA expression was significantly increased in BAL cells and PBM of patients compared with controls (p<0.05). No significant difference was found in IL-4 mRNA or IL-10 mRNA expression in BAL fluid cells or PBM between the two groups. TNFalpha mRNA expression was significantly higher in BAL fluid cells of patients than controls (p<0.05). IL-13 protein levels in BAL cell culture supernatants were slightly raised in half the patients investigated but in only two controls. Immunocytochemistry detected IL-13 protein in alveolar macrophages of patients. IL-13 led to decreased TNFalpha concentrations (p<0.05). CONCLUSIONS: IL-13 expression is increased in BAL cells and PBM in sarcoidosis and IL-13 is secreted from BAL cells. Alveolar macrophages may be the cellular source. These data suggest that IL-13 might have an anti-inflammatory effect by acting on TNFalpha.

Adult↗
PubMed2002

TNFalpha, interleukin-10 and interleukin-18 expression in cells of the bronchoalveolar lavage in patients with pulmonary complications following bone marrow or peripheral stem cell transplantation: a preliminary study.

Pulmonary complications pose a major clinical problem after bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). The underlying pathophysiological mechanisms are under investigation. Twenty patients with infectious or non-infectious pulmonary complications after BMT or PBSCT underwent bronchoalveolar lavage (BAL) and tumor necrosis factor-alpha (TNFalpha), interleukin-10 (IL-10) and interleukin-18 (IL-18) mRNA expression was determined in BAL cells in comparison to 11 healthy volunteers. Patients were divided into two groups (infectious pneumonia, n = 14 or idiopathic pneumonia syndrome (IPS)/bronchiolitis obliterans (BO), n = 6). TNFalpha expression was significantly increased in both patient groups compared to the control (0.40 +/- 0.07 and 0.39 +/- 0.09 vs 0.15 +/- 0.05; P < 0.05; semiquantitative PCR analysis; mean +/- s.e.m.). IL-10 expression was significantly elevated the group of patients with infectious pneumonia in comparison to normal controls (0.15 +/- 0.06 vs 0.01 +/- 0.01; P < 0.05) but not in patients with IPS/BO (0.05 +/- 0.04; P > 0.05). However, IL-10 was not expressed in BAL cells of all patients and control individuals. IL-18 expression was significantly decreased in the both patient groups (1.47 +/- 0.24 and 1.79 +/- 0.63) in comparison to the control group (4.29 +/- 0.77; P < 0.05). Survival analysis showed a significant association between elevation of TNFalpha and poor prognosis (P < 0.05). These results highlight the immunoregulatory disturbances in the lungs after BMT/PBSCT.

Adult↗
PubMed2001

Positron emission tomography in the staging of small-cell lung cancer : a preliminary study.

STUDY OBJECTIVES: Small-cell lung cancer (SCLC) has an unfavorable prognosis, especially when the disease is extensive at presentation. Accurate staging procedures are therefore needed for treatment planning. Positron emission tomography (PET) is a modern noninvasive imaging technique, the value of which for the staging of SCLC was investigated in the present study. SETTING: University hospital. PATIENTS: Thirty-one patients with suspected lung cancer were investigated for staging purposes using chest radiography, CT of the thorax and abdomen, abdominal ultrasound, and bone scanning. Twenty-five patients also received PET examinations during the staging procedures. Five of these patients were found to have SCLC, while two patients had mixed lesion types. Further analysis of the latter group was carried out. RESULTS: PET detected the primary tumor in all patients, and lymph nodes in five patients. All lymph nodes were proved to be malignant by endoscopic ultrasonography-guided fine-needle aspiration. Only one patient had distant metastases, which were detected by both CT and PET. CONCLUSIONS: PET appears be a suitable imaging method in SCLC. A potential role for the technique as a standard staging procedure will need to be tested by investigating a larger number of patients in a prospective study.

Bone and Bones↗
PubMed2000

Mediastinal lymphadenopathy in patients with or without previous malignancy: EUS-FNA-based differential cytodiagnosis in 153 patients.

OBJECTIVE: Mediastinal lymphadenopathy (ML) is a cause for concern, especially in patients with previous malignancy. The investigation of choice is thoracic CT with a variable sensitivity and specificity requiring tissue diagnosis. We used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for cytodiagnosis of ML in patients with and without previous malignancy. The cause, distribution of lesions, and incidence of second cancers were investigated. METHODS: Linear echoendoscopes and 22-gauge needles for cytology were used for EUS-FNA. A cytological diagnosis of malignancy was accepted, and histology or consistent follow-up of at least 9 months confirmed benign results. RESULTS: One hundred fifty-three patients underwent EUS-FNA between November 1997 and November 1999 (mean age, 60 yr; range, 13-82 yr; 105 men). Cytology was adequate in 150 patients. Final diagnosis was malignancy in 84 and benign in 66 patients (sensitivity, specificity, and diagnostic accuracy: 92%, 100%, 95%, respectively). In 101 patients without previous cancer cytology identified 48 malignant (lung, 41; extrathoracic, 7) and 51 benign lesions (inflammation, 35; various, 9; sarcoidosis, 7) (sensitivity, specificity, accuracy: 88%, 100%, 94%). Fifty-two patients had prior malignancy, mostly in extrathoracic sites. Cytology revealed recurrences in 21 patients, second cancer in 9 and benign lesions in 21 patients (inflammatory, 11; sarcoidosis, 8; tuberculosis, 1; abscess, 1) (sensitivity, specificity, accuracy: 97%, 100%, 98%). CONCLUSIONS: In patients without previous cancer malignant ML originates from the lung >80%. In those with previous malignancy recurrence of extrathoracic sites is the major cause. Benign lesions and treatable second cancers occur in a significant frequency, emphasizing the need for tissue diagnosis. EUS-FNA is a safe and minimally invasive alternative for cytodiagnosis in the mediastinum.

Adolescent↗
PubMed2000

Role of transesophageal endosonography-guided fine-needle aspiration in the diagnosis of lung cancer.

STUDY OBJECTIVE: Bronchoscopic methods fail to diagnose lung cancer in up to 30% of patients. We studied the role of transesophageal endosonography (EUS)-guided fine-needle aspiration (FNA; EUS-FNA) in such patients. DESIGN: Prospective study. The final diagnosis was confirmed by cytology, histology, or clinical follow-up. SETTING: University hospital. PATIENTS: Thirty-five patients (30 male and 5 female; mean age, 60.9 years; range, 34 to 88 years) with suspected lung cancer in whom bronchoscopic methods failed. Patients with a known diagnosis, recurrence of lung cancer, or mediastinal metastasis from an extrathoracic primary were excluded. INTERVENTIONS: EUS and guided FNA of mediastinal lymph nodes. RESULTS: The procedure was uneventful, and material was adequate in all. The final diagnosis by EUS-FNA was malignancy in 25 patients (11 adenocarcinoma, 10 small cell, 3 squamous cell, and 1 lymphoma) and benign disease in 9 patients (5 inflammatory, 2 sarcoidosis, and 2 anthracosis). Another patient with a benign result had signet-ring cell carcinoma diagnosed on pleural fluid cytology (probably false-negative in EUS-FNA). The sensitivity, specificity, accuracy, and positive and negative predictive values were 96, 100, 97, 100, and 90%, respectively. There were no complications. Reviewing the EUS morphology, the nodes were predominantly located in levels 7 and 8 of American Thoracic Society mediastinal lymph node mapping (subcarinal and paraesophageal region). In seven patients, the punctured nodes were < 1 cm (four malignant and three benign), which are difficult to sample by other methods. The malignant nodes had a hypoechoic, homogenous echotexture. CONCLUSIONS: EUS-FNA is a safe, reliable, and accurate method to establish the diagnosis of suspected lung cancer when bronchoscopic methods fail, especially in the presence of small nodes.

Adult↗
PubMed2000

Diagnosing sarcoidosis using endosonography-guided fine-needle aspiration.

STUDY OBJECTIVES: The ability to diagnose sarcoidosis cytologically has been reported previously, but the method is rarely used. Endoscopic ultrasonography (EUS) is a sensitive technique for detecting mediastinal lymph nodes, which in addition provides an opportunity to carry out guided fine-needle aspiration (FNA) cytology. We report herein on the use of EUS-FNA in the diagnosis of sarcoidosis. PATIENTS AND METHODS: Nineteen patients with suspected sarcoidosis were investigated using EUS-FNA with a linear echoendoscope and a 22-gauge Hancke-Vilman needle. MEASUREMENTS AND RESULTS: In all 19 patients, EUS revealed enlarged mediastinal lymph nodes (mean size, 2.4 cm), located subcarinally (n = 15), in the aortopulmonary window (n = 12), or in the lower posterior mediastinum (n = 5). The nodes had an isoechoic or hypoechoic appearance, with atypical vessels in five cases. The amount of aspirate obtained using EUS-FNA was adequate in all patients, and contained blood in excess of normal in some, indicating a high degree of vascularity. Cytology demonstrated epithelioid cell granuloma formation, suggesting sarcoidosis. Mycobacterial cultures were negative in all of the patients except one, in whom the final diagnosis was tuberculosis. The specificity and sensitivity of EUS-FNA in the diagnosis of sarcoidosis were 94% and 100%, respectively. CONCLUSIONS: EUS of mediastinal lymph nodes in sarcoidosis reveals certain characteristic features. However, it is not capable of differentiating the lesions from tuberculosis or malignancy. EUS-FNA is a safe and sensitive method of aspirating material for cytology and mycobacterial cultures. We believe it will provide a useful alternative in the diagnosis of sarcoidosis.

Adult↗
PubMed1996

Differential cytokine expression in human blood monocyte subpopulations: a polymerase chain reaction analysis.

The subpopulation of strongly CD14-positive (CD14++) monocytes and monocytes coexpressing the CD16 antigen and low levels of CD14 (CD14+/CD16+ cells) were isolated by fluorescence-activated cell sorting (FACS) followed by stimulation with lipopolysaccharide (LPS) at 1 micrograms/mL. Polymerase chain reaction (PCR) after reverse transcription of isolated mRNA (RT-PCR) revealed similar levels of tumor necrosis factor (TNF) transcripts in both subpopulations. By contrast, transcripts for interleukin-10 (IL-10) were only detectable in CD14++ monocytes, whereas CD14+/CD16+ cells produced no detectable IL-10 transcripts after 4 hours. Only after 16 hours of LPS stimulation was a low level of IL-10 transcripts discernible in CD14+/CD16+ monocytes. The same pattern was seen at the protein level in that TNF in LPS-stimulated supernatants was comparable for both subpopulations, whereas IL-10 was detected in CD14++ monocytes but not in CD14+/CD16+ cells. To avoid interference of cell activation by CD14 and CD16 antibodies, cells were also isolated based on the high and low level of CD33 antigen expression. Again, weakly CD33-positive cells, which comprise the CD14+/CD16+ cells, showed no or only minimal IL-10 mRNA. When comparing blood monocyte subpopulations with alveolar macrophages (AM), AM showed high levels of LPS-stimulated TNF, whereas IL-10 transcripts were undetectable. Our data show that CD14+/CD16+ blood monocytes produce high levels of proinflammatory cytokines like TNF, whereas the anti-inflammatory IL-10 is low or absent, a pattern similar to what is seen in AM.

Base Sequence↗
PubMed1996

Determination of gamma/delta and other T-lymphocyte subsets in bronchoalveolar lavage fluid and peripheral blood from patients with sarcoidosis and idiopathic fibrosis of the lung.

We measured five different lymphocyte subpopulations, including gamma/delta-T cells, in peripheral blood and bronchoalveolar lavage (BAL) fluid from 48 consecutive patients undergoing diagnostic BAL (patients with sarcoidosis (n = 19), patients with idiopathic pulmonary fibrosis (IPF; n = 11) and patients with other diseases of the lung). Quantitative analysis of CD3+, CD4+, CD8+, CD16/56+ cells and gamma/delta-T cells was done by flow cytometry. The proportion of CD3+ and CD4+ cells in the peripheral blood of patients with sarcoidosis and IPF was significantly diminished, while CD8+ lymphocytes and NK cells were significantly elevated compared to healthy controls. There was no significant difference for the gamma/delta-T cell subpopulation between patients with sarcoidosis, IPF and control group. The proportion of CD3+ and CD4+ cells in BAL fluid was significantly elevated in sarcoidosis compared to IPF, while CD8+ cells were significantly diminished. Natural killer cells, defined as CD16/56+ CD3- cells, showed comparable low numbers in sarcoidosis and IPF. For gamma/delta-T cells no significant difference was found between patients with sarcoidosis and IPF.

Adult↗
PubMed1995

ICAM-1 expression on alveolar macrophages and in serum of sarcoidosis patients.

The intercellular adhesion molecule-1 (ICAM-1) is important in mediating intercellular contact in inflammation. Therefore, we have analyzed the expression of this molecule on alveolar macrophages (AM) and in serum of patients with sarcoidosis. Bronchoalveolar lavage (BAL) cells from 13 patients and 11 control donors were stained with an anti ICAM-1 monoclonal antibody (mAb) or an isotype control. Alkaline phosphatase was used as a detection system, followed by digital single cell image analysis. Soluble ICAM-1 in serum (ssICAM-1) was determined by enzyme linked immunoassay (Elisa). Immunocytochemistry revealed a strong increase of ICAM-1 expression on AM from sarcoidosis patients (64%) compared to healthy controls (30%). Furthermore, patients exhibited a fourfold higher antigen density. Serum levels of sICAM-1 were more than twofold increased in the patient group (805.4 micrograms/ml) compared to healthy controls (384.8 micrograms/ml). SsICAM-1 showed an inverse correlation with vital capacity (VC) and diffusing capacity (DCO). This significant correlation with impairment of two important lung function parameters suggests that ssICAM-1 might be useful in serological assessment of disease activity in sarcoidosis.

Adult↗
PubMed1994

Constitutive nuclear NF-kappa B in cells of the monocyte lineage.

In monocytes, the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes, of cell-surface receptors and in the expression of human immunodeficiency virus. In such cells, DNA binding activity of NF-kappa B can be detected without intentional stimulation. In our studies, cells of the human monocytic line Mono Mac 6, cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide (LPS), also exhibit such 'constitutive' NF-kappa B, as demonstrated by mobility-shift analysis of nuclear extracts. This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted. Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B. By contrast, treatment of cells with pyrrolidine dithiocarbamate (PDTC) will only block LPS-induced NF-kappa B, but not the constitutive binding protein. Using LPS-free and serum-free conditions, constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage (HL60, U937, THP-1, Mono Mac 1 and Mono Mac 6), but not in Molt 4 T cells or K562 stem cells. When ordered according to stage of maturation, the amount of constitutive NF-kappa B was not increased in more mature cell lines. Furthermore, when inducing differentiation in Mono Mac 6 cells, with vitamin D3, no change in constitutive or inducible NF-kappa B can be detected. Analysis of primary cells revealed substantial constitutive NF-kappa B-binding activity in blood monocytes, pleural macrophages and alveolar macrophages. The constitutive NF-kappa B appears to be functionally active, since a low level of tumour necrosis factor (TNF) transcript is detectable in monocytes, and this level can be increased by blocking transcript degradation using cycloheximide. The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages. Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF, interleukin 6, interleukin 10, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor, since neutralizing antibodies did not reduce constitutive DNA-binding activity. Furthermore, blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
PubMed1994

Increased levels of soluble serum interleukin-2 receptor in extrinsic allergic alveolitis correlate with interleukin-2 receptor expression on alveolar macrophages.

In a group of 20 patients with extrinsic allergic alveolitis (10 with farmer's lung, 9 with bird-breeder's lung, and 1 with humidifier's lung), we observed increased levels of soluble serum interleukin-2 receptor (ssIL-2R) with an average of 75.2 pmol (control group average, 40.6 pmol). Analysis of bronchoalveolar lavage cells by immunocytochemistry with a CD25 antibody revealed only a slight increase to 4.2% IL-2R+ cells among alveolar lymphocytes but a pronounced rise to 21.2% IL-2R+ cells among alveolar macrophages. Furthermore, cytometry revealed a fourfold higher IL-2R expression on a per cell basis for alveolar macrophages as compared with alveolar lymphocytes. A clear-cut positive correlation (p = 0.006) was found for ssIL-2R and IL-2R+ alveolar macrophages, but only a borderline correlation was found for ssIL-2R and IL-2R+ alveolar lymphocytes (p = 0.04). The finding of a concomitant decrease of IL-2R+ alveolar macrophages and of ssIL-2R on allergen avoidance further supports the notion that alveolar macrophages may be the main source of the increased ssIL-2R in patients with extrinsic allergic alveolitis.

Adult↗