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  • 1
    Electronic Resource
    Electronic Resource
    Blood inflammatory response to inhaled endotoxin in normal subjects (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previously we have reported that in asthmatics an inhalation of 20 μg lipopolysaccharide (LPS) produces a bronchial obstruction associated with an inflammatory blood response. The aim of the present study was to evaluate this response in normal subjects. Eight normal non-atopic subjects were challenged by inhalation of a solution containing 20 μg LPS (from Escherichia coli 026:B6) a week after bronchial challenge with control solution. The lung function response was evaluated by the changes in forced expiratory volume in one second (FEV1), in specific conductance and in airway resistance while the blood inflammatory response was evaluated by serial measures of total white blood cells (WBC) and polymorphonuclear neutrophils (PMN) count, luminol enhanced-chemiluminescence (luminol-CL, as a marker of the PMN degree of activation), C-reactive protein (CRP), haptoglobin, complement fraction C3, tumour necrosis factor-α (TNF-α) and adrenocorticotropic hormone (ACTH). No response in lung function was observed for 6 h after the LPS inhalation. The count in WBC and PMN increased 300 (P 〈 0.01) and 360 (P 〈 0.01) min after the LPS challenge associated with an increase in the level of luminol-CL (P 〈 0.001). This rise in luminol-CL level was significant at 120 min (P 〈 0.05) before any change in the PMN count. After 24 and 48 h the acute-phase protein CRP raised significantly (P 〈 0.01), the other proteins C3 and haptoglobin being unchanged. A slight increase in ACTH was observed 240 and 360 min (P 〈 0.05) after the LPS challenge while the TNFα detectable level was not modified. In conclusion, in normal subjects, inhalation of a pro-inflammatory agent is able to induce a systemic inflammatory response in the absence of any effect on lung mechanics, while in asthmatics the same bronchial challenge has been reported to induce a similar blood inflammation associated with a significant response in lung function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1995.tb01005.x
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  • 2
    Electronic Resource
    Electronic Resource
    Circulating concentrations of interleukin-6 in cancer patients and their pathogenic role in tumor-induced hypercalcemia (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 286-290 
    Details
    ISSN: 1432-0851
    Keywords: Cytokines ; Interleukin-6 ; Cancer ; Bone metastases ; Hypercalcemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Circulating interleukin-6 (IL-6) concentrations correlate with disease activity in severe inflammatory conditions, in sepsis and in some hematological malignancies. On the other hand, IL-6 is a potent stimulator of osteoclastogenesis and has been implicated as a contributory factor in the genesis of osteopenic conditions. We measured circulating IL-6 levels by a sensitive (detection limit of 10 U/ml) and specific bioassay in 103 patients with advanced cancer, including 41 with tumor-induced hypercalcemia before any specific hypocalcemic therapy. We related IL-6 concentrations to clinical features and to biochemical parameters of bone metabolism, including blood Ca, Ca2+, Pi, intact parathyroid hormone, parathyroid hormone-related protein, osteocalcin, 1,25-(OH)2-vitamin D and, as markers of bone resorption, the fasting urinary excretion of calcium (Ca/creatinine) and hydroxyproline. IL-6 levels were increased, i.e. detectable, in 23% of the patients, 8/41 (20%) hypercalcemic and 16/62 (26%) normocalcemic patients (NS); the distribution of the values was similar in the two groups. The presence of increased IL-6 concentrations was not related to any clinical characteristic, notably not to the survival nor to the existence of bone metastases, whether in hypercalcemic or normocalcemic patients; e.g., only 3/12 (25%) hypercalcemic subjects without bone metastases had elevated IL-6 levels. We found no significant correlations between IL-6 concentrations and any of the biochemical parameters studied. Hypercalcemic subjects with increased IL-6 had higher urinary Ca/creatinine levels than patients with normal IL-6 levels (P〈0.005) but this was not the case in normocalcemic subjects. Mean concentrations of inflammatory or other bone metabolism markers were not significantly different between patients with normal or with elevated IL-6 levels. In summary, circulating IL-6 levels were increased in 23% of 103 patients with advanced cancer, but the frequency of increased IL-6 concentrations was not related to the presence of hypercalcemia or to any marker of calcium metabolism or bone turnover. The pathogenic importance of circulating IL-6 in patients with solid tumors remains to be demonstrated and our data indicate that increased circulating levels of IL-6, possibly reflecting the activation of the immune system, only contribute in a minor way to the osteolytic process in patients with tumor-induced hypercalcemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01519980
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  • 3
    Electronic Resource
    Electronic Resource
    Circulating concentrations of interleukin-6 in cancer patients and their pathogenic role in tumor-induced hypercalcemia (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 286-290 
    Details
    ISSN: 1432-0851
    Keywords: Key words: Cytokines – Interleukin-6 – Cancer – Bone metastases – Hypercalcemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Circulating interleukin-6 (IL-6) concentrations correlate with disease activity in severe inflammatory conditions, in sepsis and in some hematological malignancies. On the other hand, IL-6 is a potent stimulator of osteoclastogenesis and has been implicated as a contributory factor in the genesis of osteopenic conditions. We measured circulating IL-6 levels by a sensitive (detection limit of 10 U/ml) and specific bioassay in 103 patients with advanced cancer, including 41 with tumor-induced hypercalcemia before any specific hypocalcemic therapy. We related IL-6 concentrations to clinical features and to biochemical parameters of bone metabolism, including blood Ca, Ca2+, Pi, intact parathyroid hormone, parathyroid hormone-related protein, osteocalcin, 1,25-(OH)2-vitamin D and, as markers of bone resorption, the fasting urinary excretion of calcium (Ca/creatinine) and hydroxyproline. IL-6 levels were increased, i. e. detectable, in 23% of the patients, 8/41 (20%) hypercalcemic and 16/62 (26%) normocalcemic patients (NS); the distribution of the values was similar in the two groups. The presence of increased IL-6 concentrations was not related to any clinical characteristic, notably not to the survival nor to the existence of bone metastases, whether in hypercalcemic or normocalcemic patients; e. g., only 3/12 (25%) hypercalcemic subjects without bone metastases had elevated IL-6 levels. We found no significant correlations between IL-6 concentrations and any of the biochemical parameters studied. Hypercalcemic subjects with increased IL-6 had higher urinary Ca/creatinine levels than patients with normal IL-6 levels (P 〈0.005) but this was not the case in normocalcemic subjects. Mean concentrations of inflammatory or other bone metabolism markers were not significantly different between patients with normal or with elevated IL-6 levels. In summary, circulating IL-6 levels were increased in 23% of 103 patients with advanced cancer, but the frequency of increased IL-6 concentrations was not related to the presence of hypercalcemia or to any marker of calcium metabolism or bone turnover. The pathogenic importance of circulating IL-6 in patients with solid tumors remains to be demonstrated and our data indicate that increased circulating levels of IL-6, possibly reflecting the activation of the immune system, only contribute in a minor way to the osteolytic process in patients with tumor-induced hypercalcemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01519980
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Meropenem versus ceftazidime as empirical monotherapy for febrile neutropenic cancer patients (2000)
    Springer
    Annals of hematology 79 (2000), S. 152-157 
    Details
    ISSN: 1432-0584
    Keywords: Key words Ceftazidime ; Immunocompromised host ; Glycopeptide ; Infections ; Meropenem ; Neutropenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A total of 101 cancer patients with 121 febrile neutropenia episodes were randomised to receive empirical treatment with i.v. meropenem (1 g/8 h) or ceftazidime (2 g/8 h). After 3 days, 89% of patients were on unmodified therapy in the meropenem group, compared with 83% in the ceftazidime group. Of the evaluable episodes (n=106), the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime (48% vs 38%, P=0.39). Furthermore, initial success with further infections was observed in 22% of episodes treated with meropenem and in 13% of episodes treated with ceftazidime. Glycopeptides were used as first modification in 28% and 39% of meropenem and ceftazidime recipients, respectively. Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures. No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes. In conclusion, meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050571
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  • 5
    Electronic Resource
    Electronic Resource
    Anaerobic bacteremia in a cancer center (1993)
    Springer
    Supportive care in cancer 1 (1993), S. 250-255 
    Details
    ISSN: 1433-7339
    Keywords: Anaerobes ; Bacteremia ; Cancer ; Bacteroides ; Clostridium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seventy-five episodes of clinically relevant anaerobic bacterial bacteremia observed in cancer patients were reviewed. Gastrointestinal (22.7%), hematological (22.7%) and female genital tract (18.6%) cancers were the most common underlying malignant diseases. Among 84 strains of strict anaerobic bacteria recovered in the 75 patients, gram-negative rods were isolated in 49 patients (58.3%), gram-positive rods in 29 patients (34.5%) and gram-positive cocci in 6 patients (8%). Bacteroides spp. and Clostridium spp. were the most frequent pathogens (85.7%). Twenty-one episodes of bacteremia were polymicrobial, aerobic gram-positive cocci being the most frequently associated pathogens. When identified, the primary sites were the gastrointestinal tract (40%), the female genital tract (17.3%), skin and soft tissue (14.6%), the oropharynx (12%) and the lower respiratory tract (6.7%). The source remained unknown in 7 cases (9.3%). The overall survival (evaluated 10 days after the occurrence of bacteremia) was 82.5%. There was no difference in mortality between patients with monomicrobial and polymicrobial bacteremia. Pulmonary complications were more frequent in patients with fatal outcome in comparison to patients who survived. The mortality rate of the patients adequately treated was 10.3% compared to 41% for the patients not treated or treated inadequately (P=0.016, X2).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00366044
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Rationale for using TNFα and chemotherapy in regional therapy of melanoma (1994)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 56 (1994), S. 52-61 
    Details
    ISSN: 0730-2312
    Keywords: melanoma ; TNFα ; isolation perfusion ; melphalan ; interferon-γ ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Recombinant tumor necrosis factor-alpha (rTNFα) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNFα is hampered by severe systemic side-effects. The maximum tolerated dose range from 350 to 500 mg/m2, which is at least 10-fold less than the efficient dose in animals. Isolation perfusion of the limbs (ILP) allows the delivery of high dose rTNFα in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNFα with chemotherapy, with interferon-y, and with hydperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response, compared with 52% after ILP with melphalan alone. Release of nanograms levels of TNFα in the systemic circulation was evident but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this prtocol is due to a dual targeting: rTNFα activates and electively lyses the tumor endothelial cells while melphalan is mainly cytoxic to the tumor cells. ILP with rTNFα appears to be a useful model for studying the biochemotherapy of cancer in man.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240560110
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