Search PubMed⌕ Search

Biomedical subjects

A Waage

Publications and source records attributed to A Waage.

At least 55 records · Page 3Linked to original sources
PubMed1998

A population-based survey of biliary surgery in Norway. Relationship between patient volume and quality of surgical treatment.

BACKGROUND: A registry was initiated in order to establish national standards for the quality of surgical treatment of gallstones, and to provide feedback to all hospitals about serious complications, in order to reduce their future incidence. METHODS: Prospective registration of complications was performed at all hospitals and collected in the National Norwegian Cholecystectomy Registry (NNCR) over a period of 33 months. RESULTS: Open cholecystectomy (OC) was performed in 1011 patients, and laparoscopic cholecystectomy (LC) in 4332 patients. These figures represent 68% of all procedures performed nationally. The frequency of bile duct (BD) injury was 0. 8% for LC versus 0.7% for OC (ns); mortality was 0.1% versus 2.1%, respectively (p < 0.05). The frequency of BD injury and mortality were added; the sum comprised the Severe Complication Index (SCI). A linear relationship was found between SCI and patient volume (correlation coefficient, r22 = 0.78). CONCLUSIONS: SCI was found to be the best indicator of surgical success. We have proposed its use as a parameter for a future prospective quality assurance program, along with patient volume.

Cholecystectomy↗
PubMed1997

Pulmonary embolism: detection with MR perfusion imaging of lung--a feasibility study.

PURPOSE: To evaluate the feasibility of magnetic resonance (MR) perfusion imaging in the human lung to help detect perfusion defects distal to suspected pulmonary embolism. MATERIALS AND METHODS: Seven patients suspected of having pulmonary embolism first underwent ventilation-perfusion lung scintigraphy followed by MR perfusion imaging with rapid acquisition of two sets of dynamic images in the coronal and transaxial planes. A bolus of 0.05 mmol per kilogram of body weight gadopentetate dimeglumine or gadodiamide was administered. Single images obtained in each section that showed peak signal intensity from the first passage of contrast material were evaluated visually. An analysis of change in signal intensity over time was performed both on a pixel-by-pixel basis and in selected regions of interest. RESULTS: In the seven patients, a total of 18 regions of lung tissue with perfusion defects were shown on the ventilation-perfusion scans. In 16 of these regions, MR perfusion images showed a reduced peak signal intensity during first passage of the contrast agent. Perfusion defects could be detected in both the coronal and the transaxial planes on MR perfusion images. CONCLUSION: MR perfusion imaging was feasible for detection of perfusion defects distal to a pulmonary embolism.

Adult↗
PubMed1997

The influence of growth hormone on tumour necrosis factor and neutrophil leukocyte function in sepsis.

The aim of this study was to assess the influence of growth hormone (GH) in sepsis on the immune system represented by the circulating TNF-levels and the neutrophil leukocytes phagocytic capacity and respiratory burst, 22 piglets were randomized to 3 groups; pretreatment with GH (16 i.u.) before sepsis (n = 8), non-treated septic controls (n = 8), and non-septic controls (n = 6). Sepsis was induced by a standardized infusion of live E. coli. TNF was measured by a cytotoxic bioassay, while neutrophil function tests were carried out by flowcytometric assays. In brief, phagocytosis was evaluated by the neutrophils' ability to ingest FITC-labelled (fluorescein isothiocyanate) E. coli and intracellular release of oxygen metabolites was detected by the oxidation of 2',7'-dichlorofluorescin (DCFH) to the fluorescent 2',7'-dichlorofluorescein (DCF). Our data show a suppression of phagocytosis in the GH-treated group before sepsis; however, when challenged with Gram-negative bacteria, the phagocytic capacity was similar to that of the non-treated animals. The serum levels of TNF in the non-treated septic control group were twice the levels of those in the GH-treated group, 65.7 pg/ml (septic controls) vs 32.8 pg/ml (GH). Pretreatment with a single dose of GH few hours prior to sepsis does not seem to entail any further imbalance of the neutrophil function in sepsis. Lowering of the circulating TNF-levels is a presumptive favourable effect of GH in sepsis.

Animals↗
PubMed1996

Hepatocyte growth factor and its receptor c-met in multiple myeloma.

We have examined whether the hepatocyte growth factor (HGF)/c-met receptor-ligand pair is expressed in freshly isolated and highly purified myeloma cells and whether HGF can be found in the sera of myeloma patients. Myeloma cells were purified with an immunomagnetic method using the syndecan 1-specific antibody B-B4. HGF and c-met mRNA in these cells were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). HGF and c-met proteins were detected by enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively. Serum from 13 myeloma patients was obtained at diagnosis and the levels of HGF were determined by ELISA. HGF and c-met mRNA were expressed in all examined samples (n = 7). HGF was detected in the supernatants of 17 of 20 primary cultures of myeloma cells, whereas bone marrow mononuclear cells from normal controls did not produce detectable amounts of HGF (n = 3). The mean HGF level in serum of myeloma patients at diagnosis was more than fourfold higher than the mean level in normal controls. Possible implications of HGF/c-met expression for the pathophysiology of multiple myeloma are discussed.

Bone Marrow↗
PubMed1996

Concomitant expression of hepatocyte growth factor/scatter factor and the receptor c-MET in human myeloma cell lines.

Myeloma cell line supernatants were screened for their ability to inhibit the activity of transforming growth factor-beta (TGFbeta) in the mink lung cell (Mv-1-Lu) bioassay. Supernatant from the human myeloma cell line JJN-3 contained potent TGFbeta antagonistic activity. This activity was isolated and found to be associated with a 72-78-kDa glycoprotein. Specific polyclonal and monoclonal antibodies were generated toward the 72-78-kDa protein, and these antibodies precipitated the TGFbeta inhibitory activity from JJN-3 supernatant. Upon amino acid sequencing the protein appeared to be identical to hepatocyte growth factor (HGF), and some of the generated antibodies directly blocked the action of recombinant HGF in various assays. By HGF-specific polymerase chain reaction we demonstrated that HGF mRNA was expressed in five out of five tested myeloma cell lines. The level of HGF protein in supernatants showed great variation from >500 ng/ml in JJN-3 supernatant to a few ng/ml in the supernatants from other myeloma cell lines. The same five cell lines were also screened for expression the HGF receptor c-MET. Four of them expressed the receptor as shown by reverse transcriptase-polymerase chain reaction and Western blot. The receptor was shown to be constitutively phosphorylated in the human myeloma cell line JJN-3. This receptor could be dephosphorylated by anti-HGF antibodies, indicating the existence of an autocrine HGF loop in this cell line. We propose that HGF/c-MET may play a role in multiple myeloma.

Animals↗
PubMed1996

TNF receptors in murine Candida albicans infection: evidence for an important role of TNF receptor p55 in antifungal defense.

TNF mediates multiple biologic activities through two distinct cell surface receptors, TNFR-p55 and TNFR-p75. TNF plays an important role in nonspecific resistance against the fungus Candida albicans. We used transgenic mice deficient for TNFR-p55 or TNFR-p75 to investigate the role of the TNFR in antifungal defense. Mice deficient for TNFR-p55 have highly impaired ability to clear infection with C. albicans and readily succumb to the infection. Also mice deficient for TNFR-p75 had a significant reduction in their ability to clear the fungus although lethality was not increased. These data demonstrate that TNFR-p55 in particular, but also TNFR-p75, plays a definite role in defense against infection with C. albicans. In NMRI mice, infection with C. albicans resulted in a significant systemic release of soluble (s)TNFR-p75. Cyclophosphamide-induced granulocytopenia led to a reduction of sTNFR-p75 release, whereas levels of bioactive TNF in response to fungal infection were increased. Release of sTNFR-p55 was not affected by induction of granulocytopenia. These observations suggest that granulocytes are a source of sTNFR-p75, possibly contributing to regulation of TNF activity during infection with C. albicans.

Animals↗
PubMed1996

[Treatment with growth factors and cytokines in hematologic diseases].

The Norwegian Society of Haematology has worked out guidelines for the use of granulocyte-colony stimulating factor and granulocyte-monocyte colony stimulating factor and interferon alpha in clinical haematological practice. We recommend not using growth factors as a routine to prevent or to treat fever in patients with granulocytopenia induced by cytostatics, or patients with myelodysplastic syndromes. At present such treatment should be restricted to clinical trials. The same conclusion was reached in regard to use of erythropoietin in the case of myelodysplastic syndromes. Harvesting of stem cells from peripheral blood is a well documented indication for administration of growth factors. Interferon alpha as maintenance treatment for cases of multiple myeloma and low grade malignant lymphoma delays progression of the disease but does not improve chance of survival. There is no documentation of improved quality of life. Use of interferon alpha is not justified as a routine treatment for multiple myeloma. In chronic myelogenous leukemia, interferon alpha seems to be equal to or better than hydroxyurea, and may be considered for patients who cannot undergo allogeneic bone marrow transplantation.

Cytokines↗
PubMed1996

Hepatocyte growth factor reverses the TGF-beta-induced growth inhibition of CCL-64 cells. A novel bioassay for HGF and implications for the TGF-beta bioassay.

The influence of human hepatocyte growth factor (HGF) on the transforming growth factor beta (TGF-beta) bioassay CCL-64 was examined. HGF induced proliferation of the CCL-64 cells and potently counteracted TGF-beta-induced growth inhibition. HGF was not inactivated by transient acidification to pH 2, a commonly used procedure to activate latent TGF-beta. HGF was a stronger mitogen for the mink lung cells than epidermal growth factor (EGF), a known stimulator of CCL-64 cell growth. Costimulation of the cells by these two cytokines resulted in an additive effect on proliferation. In complex biological fluids containing large amounts of HGF, the TGF-beta concentration can be underestimated when determined by the CCL-64 assay. When a fixed amount of TGF-beta is added, the CCL-64 cells can be used as a reliable bioassay for HGF with a sensitivity of about 1 ng/ml.

Animals↗
PubMed1996

Comparison of the effects of 2-chlorodeoxyadenosine and melphalan myeloma cell lines.

We have studied the effects of 2-chlorodeoxyadenosine (2-CdA) and melphalan on DNA synthesis and cell proliferation of five myeloma cell lines and one primary culture of highly purified myeloma cells. The DNA synthesis was estimated by thymidine incorporation and cell death was estimated by a coluorimetric assay sensitive to mitochondrial activity. The concentrations of 2-CdA giving 50% inhibition of DNA synthesis (ID50) in four cell lines were 8, 100, 500 and 2500 nM, whereas the corresponding concentrations of melphalan were 600, 600, 1000 and 7500 nM, respectively. In one cell line, the ID50 for melphalan was 400 nM, whereas 2-CdA apparently was without inhibitory effect and the ID50 was not reached. The ID50 for 2-CdA in the primary culture was 250 nM. When compared on a molar basis, 2-CdA had a more potent inhibitory effect than melphalan on four out of five myeloma cell lines. This is in contrast to clinical experiments which have shown lack of effect of 2-CdA in myeloma patients. Our study shows that 2-CdA has a marked heterogeneous effect on myeloma cell lines and opens up the possibility that a similar variation in sensitivity may also exist among myeloma cell clones in vivo.

Antineoplastic Agents↗
PubMed1996

Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome.

Plasma levels of cytokines were measured by EIA in 15 subjects hospitalized with nephropathia epidemica, a European form of hantavirus-induced hemorrhagic fever with renal syndrome. Concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were increased in all patients at admission, and the concentration of IL-10 was increased in most. TNF-alpha concentrations were still increased 1 week after onset of disease; levels of IL-6 and IL-10 were normalized. TNF-alpha was undetectable by the WEHI cell assay in serum samples obtained throughout the acute phase of disease. Serum levels of the two soluble TNF receptors p55 and p75 correlated with levels of the cytokine, indicating that receptor binding may be the reason for lack of bioactivity in vitro. TNF-alpha is known to induce pathophysiologic and clinical changes similar to those seen in nephropathia epidemica and in diseases caused by other hantaviruses.

Acute Disease↗
PubMed1995

[A national registry for cholecystectomy. Quality assurance with practical consequences?].

Altogether 2,120 patients have been enrolled in the Norwegian Cholecystectomy Registry during the first 18 months after it was established. 1,699 patients (80%) were operated on laparoscopically. In 174 (10.2%) the operation was changed to an open procedure. 421 (20%) were operated on primarily using an open technique. The main quality problems were mortality (1.2%) and injuries of the common bile duct (0.95%) associated with open cholecystectomy. These frequencies are far above the values stated in available literature, and two interpretations are possible: Only the best results tend to be published internationally, and our results may be representative for the national average frequencies of serious complications in other countries too. On the other hand, the present results may disclose inadequate quality insufficiency and a need for improvement. The possible actions seem to be: Firstly, to try harder to avoid open cholecystectomy in seriously ill patients (ASA 3-4). If possible, they should not be operated on at all. When surgery is essential, a laparoscopic technique seems to cause less cardiopulmonary complications. Secondly, an improved dissection technique in open (and laparoscopic) surgery is necessary in order to reduce the frequency of injuries of the common bile duct.

Aged↗
PubMed1995

Granulocytopenia reduces release of soluble TNF receptor p75 in endotoxin-stimulated mice: a possible mechanism of enhanced TNF activity.

This study demonstrates that granulocytopenia alters the TNF response to endotoxin. Significantly higher levels of bioactive TNF were observed in mice rendered granulocytopenic (< 0.05 x 10(9) granulocytes/litre) with cyclophosphamide than in normal mice. Levels of circulating soluble TNF receptor p75 (sTNFR-p75) in response to endotoxin were higher in normal mice than in granulocytopenic mice whereas no difference in levels of circulating soluble TNF receptor p55 (sTNFR-p55) was observed. To investigate further the role of both sTNFR in inactivation of TNF, murine recombinant (r) TNF or human rTNF was injected in to normal and granulocytopenic mice. Higher TNF bioactivity was recovered in granulocytopenic mice than in normal mice after administration of murine rTNF, whereas, no difference in recovered TNF bioactivity was observed after human rTNF. As murine TNFR-p75 does not bind to human TNF, this observation indicates that less sTNFR-p75 available for neutralization of TNF in the circulation in granulocytopenia results in enhanced TNF bioactivity. Furthermore, endotoxin-induced lethality was increased in granulocytopenic mice. In summary, this study shows that endotoxin-induced release of sTNFR-p75 is reduced and TNF bioactivity increased in granulocytopenia. Our data suggest that release of sTNFR-p75 from granulocytes is a mechanism in the regulation of TNF bioactivity.

Agranulocytosis↗
PubMed1995

Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase II. A report of two cases and a review of the literature.

BACKGROUND: The development of therapy-related acute myeloid leukemia (t-AML) with balanced translocations to chromosome bands 11q23 and 21q22 has recently been significantly related to previous treatment with several cytostatic drugs poisoning DNA topoisomerase II. A similar association was suspected for other balanced chromosomal aberrations such as the t(15;17) characteristic of acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Two cases of acute promyelocytic leukemia were observed following treatment for seminoma with etoposide, cisplatin, and bleomycin and treatment for breast cancer with 4-epi-doxorubicin and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil followed by radiotherapy. Both cases presented a t(15;17) (q22;q12) and were examined for the characteristic chimeric rearrangement of the RAR alpha and PML genes observed in acute promyelocytic leukemia de-novo. RESULTS: In both cases the characteristic chimeric rearrangement was demonstrated. Case no. 2 in addition to the t(15;17) showed an inversion of the long arm of a chromosome no. 5 and a del(7)(q22) in all abnormal mitoses studied. Despite these findings the patient obtained a complete morphological and cytogenetic remission of the leukemia following treatment with all-trans-retinoic acid. CONCLUSIONS: Based on these two cases and a review of the literature it is concluded that the development of t-APL with the balanced translocation t(15;17) is related to previous treatment with cytostatic drugs targeting DNA topoisomerase II and that additional abnormalities of the long arms of chromosomes no. 5 and no. 7 do not interfere with the induction of remission with all-trans-retinoic acid.

Adult↗
PubMed1995

Soluble tumour necrosis factor receptors, tumour necrosis factor and interleukin-6 in serum in granulocytopenic patients with fever.

Serum levels of TNF, IL-6 and soluble TNF receptors p55 and p75 (sTNFR-p55 and sTNFR-p75) were examined in 14 patients with acute myeloid leukaemia during 43 courses of chemotherapy. The patients experienced 30 episodes of fever which occurred during granulocytopenia (defined as granulocyte counts < 0.2 x 10(9)/l) and six fever episodes when granulocyte counts were > 1.0 x 10(9)/l. Febrile episodes were classified as microbiologically defined infection, clinically defined infection, and unexplained fever. Levels of bioactive IL-6 and immunoreactive TNF increased in response to fever during granulocytopenia, whereas bioactive TNF was not detected in any sample in this study. During granulocytopenia, both sTNFR rose significantly in microbiologically defined infection (P < 0.01 for sTNFR-p55 and P < 0.05 for sTNFR-p75), but not in the other two categories. The ratio of sTNFR-p55 to sTNFR-p75 was higher during febrile periods in granulocytopenia than in a non-granulocytopenic situation with granulocyte counts > 1.0 x 10(9)/l (P < 0.01). We conclude that granulocytopenia affects release of the two sTNFR differently during febrile periods, and that release of sTNFR-p75 in response to fever is reduced during granulocytopenia, suggesting a role for the granulocytes in systemic release of sTNFR-p75.

Acute Disease↗
PubMed1995

The involvement of CD14 in stimulation of TNF production from peripheral mononuclear cells isolated from PNH patients.

Peripheral blood mononuclear cells (PBMC) from six patients with paroxysmal nocturnal haemoglobinuria (PNH) were analysed by flow cytometry for expression of CD14 and for ability to respond to bacterial lipopolysaccharide and beta 1-4 linked polymannuronic acid by TNF secretion. Expression of cell surface CD14 could not be detected on cells from the PNH patients, whereas the levels of expression of other monocyte antigens, e.g. CD33 and CD13, were comparable to that of cells from healthy subjects. The cells from the patients with PNH responded with secretion of significantly less TNF after stimulation with LPS and polymannuronic acid than mononuclear cells from healthy subjects, suggesting an impaired ability in PNH to respond to bacterial infection by TNF secretion from monocytes. Soluble CD14 appeared to be involved in the residual activation of CD14 negative PBMC, and the sera of these patients contained normal or slightly elevated levels of soluble CD14. After allogeneic bone marrow transplantation in one patient the monocytes expressed CD14 at normal levels and responded normally with respect to their ability to generate TNF upon stimulation.

Adult↗
PubMed1995

High levels of interleukin 10 in serum are associated with fatality in meningococcal disease.

Interleukin 10 (IL-10) suppresses the production of proinflammatory cytokines in vitro and in murine models of endotoxemia and has been suggested as a candidate for treatment of bacterial septicemia. To investigate the role of IL-10 in meningococcal disease, a sandwich IL-10 enzyme-amplified sensitivity immunoassay was used to quantitate IL-10 in serum and cerebrospinal fluid samples from 41 patients with meningococcal bacteremia or meningitis with or without septic shock. High levels of IL-10 were demonstrated in sera from patients with meningococcal septic shock (mean, 21,221 pg/ml; range, 25 to 64,500 pg/ml). All cases involving fatalities had IL-10 levels in serum of > or = 1,000 pg/ml (mean, 23,058 pg/ml; range, 1,000 to 64,500 pg/ml). Patients with meningococcal meningitis without septic shock had comparably low concentrations of IL-10 in serum (mean, 119 pg/ml; range, 0 to 1,050 pg/ml) but exhibited compartmentalized release of IL-10 in cerebrospinal fluid. Concentrations of IL-10 in serum were positively correlated with the previously reported concentrations of tumor necrosis factor alpha, IL-6, and IL-8 in serum in the same patients. We conclude that IL-10 is extensively activated along with the proinflammatory cytokines during the initial phase of meningococcal septic shock and that IL-10 is associated with fatality in meningococcal disease.

Adolescent↗
PubMed1995

Plasma homocysteine levels in patients with deep venous thrombosis.

Increased risk of arterial and venous thromboembolic disease is well documented in the homocystinuric patient. There is growing evidence that hyperhomocysteinemia is an independent risk factor for premature arteriosclerotic disease, including cerebral, peripheral, and coronary vascular diseases. So far no association has been established between hyperhomocysteinemia and venous thromboembolism. We studied 35 patients, young adults (age less than 56 years) with venographically and/or ultrasonographically verified deep venous thrombosis (DVT). Patients with coexisting diseases were excluded. Plasmahomocysteine levels before and after intake of methionine were measured 3 months or more after the time of diagnosis and compared with 39 control subjects. We found no significant difference in plasmahomocysteine levels between the young adults with deep venous thrombosis and control subjects. This indicates that hyperhomocysteinemia is not a frequent cause of DVT.

Adult↗