Search PubMed⌕ Search

Biomedical subjects

K Pulkki

Publications and source records attributed to K Pulkki.

89 records · Page 5Linked to original sources

Proinflammatory mediator response in coronary bypass surgery using a centrifugal or a roller pump.

Major surgery, trauma, and infection induce a proinflammatory mediator response which, if excessive, may cause tissue injury. The response was measured during elective coronary bypass surgery when a centrifugal pump or a roller pump, differing in their basic working principles, was used for extracorporeal circulation (ECC). Eight patients were perfused with a centrifugal pump and eight patients with a roller pump during ECC. Plasma interleukin-1 beta (IL-1 beta), IL-2, IL-6, tumor necrosis factor alpha (TNF alpha), group II phospholipase A2, (PLA2), endotoxin, fibronectin and serum C-reactive protein (CRP) concentrations were measured. The operation increased plasma IL-6, group II PLA2, and serum CRP concentration and decreased plasma fibronectin concentrations. IL-1 beta and TNF alpha concentrations did not change. IL-2 occurred only occasionally, and endotoxin did not occur in any patient. No differences were seen between the group using a centrifugal pump and the group using the roller pump. Cardiac surgery with a perfusion time of less than two hours thus caused a proinflammatory mediator response which was similar whether a centrifugal or a roller pump was used for ECC.

Cardiopulmonary Bypass↗

Endotoxin, interleukin-6 and phospholipase-A2 as markers of sepsis in patients with hematological malignancies.

The concentrations of endotoxin, interleukin-6 (IL-6) and group II phospholipase-A2 (PLA2-II) were measured in serum or plasma during cytotoxic chemotherapy, fever of unknown origin and sepsis in 56 patients with hematological malignancies and during sepsis and viral infections in 22 non-hematological patients. High concentrations of IL-6, PLA2-II and endotoxin were detected in sepsis, the levels being similarly elevated in hematological and non-hematological patients. The levels of IL-6 and PLA2-II correlated closely with that of C-reactive protein (CRP). The levels of PLA2-II and IL-6 declined earlier than the level of CRP during the course of antimicrobial treatment. The levels of IL-6 also rose earlier than the level of CRP. The ability of IL-6 and PLA2-II and endotoxin to discriminate between sepsis and other causes of fever was comparable to that of CRP. IL-6 and PLA2-II are, together with CRP, valuable tools for the detection of sepsis in patients with hematological malignancies who undergo cytotoxic medication. Endotoxin is not suitable for routine laboratory diagnosis of sepsis.

Adolescent↗

Serum immunoreactive interleukin-6 and C-reactive protein levels in patients with multiple myeloma at diagnosis.

Serum bioactive but not immunoreactive interleukin-6 (IL-6), and serum C-reactive protein (CRP), have been reported to be of prognostic significance in multiple myeloma (MM). We measured serum immunoreactive IL-6 by a sensitive enzyme-linked immunosorbent assay in 30 MM patients at diagnosis. In 30% of the patients serum immunoreactive IL-6 exceeded the upper reference limit. The concentrations of CRP and IL-6 showed a linear association. Logarithmically transformed IL-6, CRP and beta 2-microglobulin were significant variables by univariate survival analysis; by multivariate analysis CRP was a slightly stronger prognostic factor than IL-6 and the only one of independent prognostic significance.

Adult↗

Head and neck cancer: effect of food ingestion on uptake of C-11 methionine.

PURPOSE: To determine the influence of a standardized meal on tumor uptake measured with positron emission tomography (PET) and L-(methyl-carbon-11) methionine. MATERIALS AND METHODS: Five patients with untreated squamous cell cancer of the head and neck underwent PET, first in a fasting state and then 6-7 days later after ingesting a liquid meal. RESULTS: All tumors were seen on PET scans, and image quality remained good after food ingestion. The standardized uptake values of the tumors were 3.7-11.4 in the fasting state but decreased after the meal (range, 3.3-10.0; P < .04). No substantial change was measured in tumor C-11 methionine influx constants (Ki values). CONCLUSION: Although cancer imaging with PET and C-11 methionine can be performed even in the patient has not fasted, a standardized meal may decrease tumor C-11 methionine uptake.

Aged↗

Generation of reference values for cardiac enzymes from hospital admission laboratory data.

An approach is described for using patient databases of a hospital information system as a source of reference values for cardiac enzymes. Of a total of 2029 emergency admission patients with serial cardiac enzyme data, 538 patients were considered "healthy" (having no damage in myocardium) because their discharge diagnoses suggested neither myocardial damage nor any other condition that could lead to elevated enzyme activities, and because their serially collected cardiac enzyme activities remained stable. Enzyme activities of creatine kinase (EC 2.7.3.2), creatine kinase isoenzyme MB, lactate dehydrogenase (EC 1.1.1.28), and lactate dehydrogenase isoenzyme 1 of these patients at admission to hospital were considered as suitable health related reference values. The upper (97.5%) reference limits of activities, measured at 37 degrees C according to Scandinavian recommendations, were as follows (age dependent limits given at 25 and at 75 years of age, U/l): creatine kinase men 268, 192; creatine kinase women 200 (no age effect); creatine kinase-MB 16, 24; lactate dehydrogenase 497, 603; lactate dehydrogenase isoenzyme 1 103, 140. For comparison, reference values were also produced conventionally from a group of 246 healthy subjects. Observed effects of age on enzyme activities were quite similar to those in the selected patient group. Calculated reference limits for isoenzymes creatine kinase-MB and lactate dehydrogenase isoenzyme 1 were also similar but reference limits for less cardiospecific total enzyme activities, creatine kinase and lactate dehydrogenase, were more variable between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

IL-2 induces IL-6 production in human monocytes.

IL-2 is a potent activator of effector and secretory activities of human monocytes. Since monocytes are an important source of IL-6, we investigated whether IL-2 can induce IL-6 production and whether regulatory circuits can modulate this process. We found that stimulation of monocytes with IL-2 induced expression of IL-6 mRNA and bioactivity in a dose-dependent manner. Production of IL-6 in monocytes can be induced by other cytokines such as IL-1 beta. By using mAb alpha-IL-1 beta we showed that IL-2-induced IL-6 production is not mediated by the autocrine stimulation of IL-1 beta elicited by IL-2. IL-6 induction by monocytes is not a common response to activating signals because IFN-gamma did not induce IL-6 expression under conditions in which it elicits tumoricidal activity. In contrast, IFN-gamma could completely abrogate the induction of IL-6 expression by IL-1 beta but did not affect the levels of mRNA and the secretion of IL-2-elicited IL-6. We have previously reported that transforming growth factor-beta inhibits IL-6 production in response to IL-1 beta. Studies on the inhibitory activity of transforming growth factor-beta demonstrated that this cytokine differs from IFN-gamma because it inhibited both IL-1- and IL-2-induced IL-6 expression. These data demonstrate that, in human monocytes, both IL-1 and IL-2 stimulate IL-6 expression by independent mechanisms that can be dissociated by the susceptibility to the inhibitory effect of IFN-gamma. IL-6 production is also down-regulated by TGF-beta, whose inhibitory activity is stimulus-unrelated.

Cells, Cultured↗

Transforming growth factor beta downregulates interleukin-1 (IL-1)-induced IL-6 production by human monocytes.

We investigated the effects of transforming growth factor beta (TGF beta) on the induction by interleukin-1 beta (IL-1 beta) of IL-6 in human monocytes. We found that IL-1 beta induced IL-6 messenger RNA expression in elutriated monocytes and IL-6 secretion in the supernatant. TGF beta did not induce IL-6. In contrast, TGF beta added to the culture inhibited, in a dose-dependent manner, the induction of IL-6 by IL-1 at the level of messenger RNA and bioactivity. These results show that IL-1 beta is able to stimulate IL-6 production by monocytes, TGF beta, by inhibiting this effect, may play an important role in regulating the IL-1-mediated components of the inflammatory response.

Blotting, Northern↗

Arthritis-associated changes in flow cytometric characteristics of cultured synovial fibroblasts.

Synovial fibroblasts cultured from patients with rheumatoid or reactive arthritis and from controls were studied by flow cytometry, spectroscopy, and electron microscopy. Analysis of 29 cell lines revealed consistent differences between arthritic and normal fibroblasts. Cells cultured from inflamed synovial tissue exhibited higher autofluorescence than did control fibroblasts, and displayed exceptional light scatter properties in flow cytometry, indicating changes in cytoplasmic structures. Electron microscopic examination of the fibroblasts from arthritic synovial tissue revealed large numbers of round, swollen, laminated, mitochondrion-like bodies, which were not observed in the control fibroblasts. The changes observed by flow cytometry (light scatter and autofluorescence) coincided with the presence of the mitochondrion-like organelles. The strong autofluorescence observed in the arthritic fibroblasts resembled the fluorescence spectrum of mitochondrial flavoproteins. These data suggest that persistent metabolic and structural changes have occurred in the mitochondria of synovial fibroblasts and inflammatory synovial tissue. The usefulness of flow cytometry in identifying such cells is described.

Arthritis↗

Abnormal mitochondria in cultured synovial fibroblasts in rheumatoid and reactive arthritis?

This paper summarizes our recent studies on synovial fibroblast cultures started from patients with rheumatoid or reactive arthritis and from healthy controls. Analysis of these cultures by flow cytometry, spectroscopy and electron microscopy revealed consistent differences between arthritic and normal fibroblasts. Increased autofluorescence, exceptional light scatter properties, rhodamine-123 staining and electron microscopic findings of fibroblasts from arthritis patients suggest involvement of mitochondria in the disease process. Conditioned media of activated monocytes induced in the mitochondria of normal synovial fibroblasts changes similar to those observed in the fibroblasts originating from patients with rheumatoid or reactive arthritis.

Arthritis, Rheumatoid↗

The effects of synovial fluid macrophages and interleukin-1 on hyaluronic acid synthesis by normal synovial fibroblasts.

The effects of peripheral blood monocyte and rheumatoid synovial fluid macrophage conditioned media were studied on hyaluronic acid (HA) metabolism of normal synovial fibroblasts. Both media stimulated HA synthesis about two-fold compared to controls (1% fetal calf serum). The activated mononuclear phagocyte conditioned media did not contain HA-degrading activity in these experiments. The effects of various concentrations of interleukin-1 (IL-1) on HA synthesis and proliferation of synovial fibroblasts were studied. Even at very low concentrations (0.1 IU IL-1/ml) HA synthesis was stimulated. With increasing concentrations HA synthesis did not increase but proliferation was stimulated. Stimulated fibroblasts synthesized mainly high molecular weight HA. Thus with IL-1-activation, normal synovial fibroblasts could not produce increased amounts of abnormal HA with decreased molecular weight.

Arthritis, Rheumatoid↗

Evaluation of a semiquantitative C-reactive protein latex slide test as compared to quantitative turbidimetric measurement in hospital laboratory practice.

Serum C-reactive protein (CRP) concentrations of 708 patients with suspected bacterial disease were estimated with a semiquantitative CRP latex slide test using cut-off levels of 20 and 40 mg/l and with quantitative turbidimetric technique. Latex slide tests gave 11.8% (80/708) discordant results. About 7% of tests gave clear disconcordant results (5% of those were positive and 2% negative tests). We conclude that CRP latex slide test is not useful in emergency laboratory in hospital material with a high incidence of bacterial infections.

Bacterial Infections↗

Four monoclonal immunoglobulins in a patient with chronic lymphocytic leukemia.

We report here the case of a 73-year-old woman with chronic lymphocytic leukemia. Two years after the diagnosis, electrophoresis of her serum showed two monoclonal fractions, but our modified immunofixation procedure revealed four monoclonal immunoglobulins in five fractions: two IgG lambda fractions, one IgG kappa fraction, one IgA kappa fraction, and one IgG kappa fraction. This is an exceptionally high number of monoclonal immunoglobulins in a single patient. In the course of her disease the patient did not show any clinical, radiological, or laboratory signs of multiple myeloma or macroglobulinemia. The different monoclonal immunoglobulins were considered to be one expression of her B-lymphocytic malignancy.

Aged↗

The effect of rheumatoid synovial fluid macrophages on DNA, glycosaminoglycan and collagen synthesis by synovial fibroblasts.

The effects of soluble factors secreted by peripheral blood monocytes and rheumatoid synovial fluid macrophages were tested on human synovial fibroblast cultures. Both monocytes and macrophages liberated factors which reduced DNA synthesis (3H-thymidine incorporation) by synovial fibroblasts. Monocyte and macrophage factors stimulated hyaluronic acid synthesis. The activation obtained with rheumatoid synovial macrophages was considerably greater than that with monocytes. Foetal bovine serum was found to have a clear stimulatory effect on the synthesis of collagen and other proteins by fibroblasts. The effects of monocyte and macrophage factors on protein synthesis in synovial fibroblasts were small: collagen synthesis was slightly increased relative to other extracellular proteins.

Arthritis, Rheumatoid↗

Effects of sodium aurothiomalate on hyaluronic acid synthesis in normal and rheumatoid synovial fibroblast cultures.

In studies with normal and rheumatoid synovial fibroblast cultures the effects of sodium aurothiomalate on the quantity and quality of hyaluronic acid were tested. This gold compound produced one clear effect: the molecular weight of hyaluronate produced by rheumatoid fibroblasts was increased (shifted towards normal) whereas the effects on the amounts of hyaluronic acid synthesized were small in both rheumatoid and control cultures. The importance of this finding in relation to the known beneficial effects of gold preparations in clinical medicine is discussed.

Adolescent↗

Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults.

BACKGROUND: Intranasally applied insulin is one of the antigen-specific therapies currently tested in clinical type 1 diabetes prevention trials, for example, in the Type 1 Diabetes Prediction and Prevention Study (DIPP). The possibility that the therapy may cause hypoglycaemia or local irritation and the poorly known immunological safety of mucosal application of the antigen in healthy subjects prompted this study. METHODS: We used a randomised, placebo-controlled, double-blinded crossover study design with 3-week treatment periods to study the effects of once-daily intranasal application of human short-acting insulin without absorption-enhancing adjuvants in 20 non-diabetic adults. The selected 60 IU dose of insulin was equivalent to the weight-based dose used for the DIPP children. We investigated self-monitored blood glucose concentrations, nasal insulin effects and induction of diabetes-associated autoantibodies. RESULTS: The two treatment periods showed no differences in blood glucose concentrations or in the frequency of blood glucose values higher than 3.0 mmol/L. Of the eight measured hypoglycaemic values, only one, which occurred during placebo therapy, was associated with symptoms. Rhinoscopy revealed no nasal irritation, and mucociliary clearance, nasal airway patency and nasal airflow resistance were not affected by the insulin therapy. Eleven subjects complained of transient nasal stinging or unpleasant odour and one subject reduced the dose because of nasal irritation. The treatment did not induce production of any of the four diabetes-associated autoantibodies. CONCLUSIONS: Short-term use of intranasal insulin without absorption enhancers was predominantly well tolerated, the risk of hypoglycaemia was minimal and no objective nasal adverse effects were detected.

Administration, Intranasal↗