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Biomedical subjects

I Christiansen

Publications and source records attributed to I Christiansen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Elevated serum levels of soluble ICAM-1 in non-Hodgkin's lymphomas correlate with tumour burden, disease activity and other prognostic markers.

The serum levels of soluble ICAM-1 (CD54) were significantly elevated in patients with non-Hodgkin's lymphomas (NHL, n=127) and hairy cell leukaemia (HCL, n=15) compared with healthy controls (n=31). In high-grade malignant NHL (n=79) the sICAM-1 levels correlated with the tumour mass as reflected in the Ann Arbor staging system but not with bulky disease. Further, the sICAM-1 levels correlated with disease activity as reflected by the presence of B symptoms and with other known prognostic markers. In particular serum thymidine kinase (sTK). In patients with low-grade malignant NHL (n=48) a trend towards higher serum levels of sICAM-1 was found in patients with advanced stage and B symptoms. In both low and high-grade malignant NHL, elevated levels of sICAM-1 were associated with poorer overall and disease-free survival. The present results indicated that sICAM-1 levels have a prognostic power equal to that of other serum markers claimed to be of prognostic value in NHL, namely serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), beta-2-microglobulin (beta2m), serum thymidine kinase (sTK), albumin and orosomucoid. The cellular origin and the possible interactions between soluble and surface ICAM-1 and its ligands needs further exploration.

Adult↗
PubMed1996

Jugular venous bulb oxyhemoglobin saturation during cardiac surgery: accuracy and reliability using a continuous monitor.

Previous studies have demonstrated the feasibility of continuously monitoring jugular venous oxygen saturation (SjO2) with a fiberoptic catheter during hypothermic cardiopulmonary bypass (CPB). In the present study, with patients maintained at either moderate (28 degrees C) or mild (32-34 degrees C) hypothermia during CPB, SjO2 values obtained from a fiberoptic catheter were compared to intermittent samples analyzed by a co-oximeter. Twenty patients scheduled for elective coronary artery or valvular surgery had a 5.5 Fr Opticath catheter inserted into the left internal jugular bulb after induction of general anesthesia. The catheter was calibrated in vitro and in vivo according to the manufacturer's specifications. Catheter and co-oximetry SjO2 values obtained at four time points--1) pre-CPB, 2) target CPB temperature, 3) mid-rewarming, and 4) post-CPB--were compared using linear regression, Bland-Altman analysis, and Shrout-Fleiss interclass correlation coefficient analysis. These statistical methods revealed poor correlation between the catheter and co-oximetry SjO2 values: r = 0.44 by linear regression and 0.32 by interclass correlation coefficient analysis, and was unacceptably discrepant by Bland-Altman analysis. Oxyhemoglobin saturation values obtained continuously from a jugular venous bulb fiberoptic catheter during CPB may not accurately reflect true oxyhemoglobin saturation, and caution is warranted when interpreting SjO2 values obtained from a fiberoptic catheter during CPB.

Aged↗
PubMed1996

Time course of platelet alpha granule release in acute myocardial infarction treated with streptokinase.

OBJECTIVE: To determine the time course of platelet alpha granule release in patients with acute myocardial infarction treated with streptokinase. DESIGN: A prospective study. SETTING: Coronary care unit. PATIENTS: Nine with myocardial infarction treated with both streptokinase and aspirin, and nine with acute chest pain but without myocardial infarction, who were treated with aspirin only. METHODS: All patients received 250 mg aspirin on admission and 150 mg once daily thereafter. All patients who fulfilled the indications for streptokinase received 1.5 megaunits, in a single infusion. After the initial medication, serial measurements of plasma beta thromboglobulin and plasma platelet factor 4 were performed at fixed intervals after the onset of chest pain. The primary endpoint sought was the peak value of beta thromboglobulin and platelet factor 4 in each individual. RESULTS: The median peak plasma beta thromboglobulin in the infarction group was substantially higher than in those without infarction, at 37 (range 12 to 210) v 15 (9 to 36) mg/litre, P < 0.01. The corresponding values for plasma platelet factor 4 were 4.6 (2.4 to 60.0) v 2.2 (< 2 to 8.5) mg/litre, P < 0.01. Increased values were seen only within the first 12 h after onset of chest pain, and after 12 h there was no difference between the patients with myocardial infarction and those without. Aspirin treatment did not abolish alpha granule release. CONCLUSIONS: In patients with acute myocardial infarction treated with streptokinase the content of the alpha granules is released within the first 12 h after the onset of chest pain. Aspirin apparently does not abolish this release.

Adult↗
PubMed1996

Oral cladribine as primary therapy for patients with B-cell chronic lymphocytic leukemia.

PURPOSE: Purine analogs have wide potential indications in the treatment of hematologic malignancies, but intravenous administration has been required. We previously established that the oral bioavailability of cladribine is 50%. Our aim was to evaluate the efficacy and toxicity of oral cladribine to previously untreated patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Sixty-three patients with symptomatic but previously untreated CLL received cladribine solution 10 mg/m2/d orally for 5 consecutive days in monthly courses. RESULTS: Complete remission (CR) was achieved in 24 patients (38%), and 23 patients (37%) had a partial response (PR). Most patients, including those in whom there was no remission (NR) achieved normal blood lymphocyte counts. Failure to meet response criteria was mostly due to thrombocytopenia. The median response duration was not reached at 2 years. The median survival time among 13 deceased patients was 322 days, whereas the median observation time of surviving patients is 760 days. The overall survival rate at 2 years is 82%. Response rate was associated with clinical stage. Grade III to IV infectious toxicity occurred in one third of patients. CONCLUSION: Orally administered cladribine is an effective and feasible therapy for CLL, and produces durable remissions in three quarters of the patients. However, significant toxicity may occur and further studies are required to assess long-term effects and quality-of-life aspects.

Administration, Oral↗
PubMed1995

Soluble ICAM-1 in Hodgkin's disease: a promising independent predictive marker for survival.

The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with the presence of B-symptoms, histology and tumour burden as reflected in the Ann Arbor staging system, but not to bulky disease. sICAM-1 was compared to other serum factors claimed to be of prognostic significance in HD, including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30 (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of these markers. In univariate regression analyses, all but ESR correlated with disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall survival. In multivariate analyses only sIL-2R (as a continuous variable) added independent prognostic information in addition to age, stage and B-symptoms. sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively) for disease-free survival. sCD30 correlated with overall survival (p = 0.03) while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as well as sIL-2R and sCD30 added independent prognostic information for both disease-free and overall survival. Based on the present observations, it appears that sICAM-1 may be a predictor for relapse and survival in HD. Determination of serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of potential value when selecting HD patients eligible for intensive therapy in clinical trials.

Female↗
PubMed1995

Effects of single and multiple intravenous cocaine injections in humans maintained on methadone.

The effects of i.v. cocaine were examined in individuals maintained on methadone. Sixteen adult methadone-maintained i.v. cocaine users, residing on a clinical research unit, participated in eight laboratory sessions under each of two conditions: cocaine 1 hr after daily methadone and cocaine 22 hr after daily methadone. The conditions were separated by an outpatient period of 3 to 5 weeks. During the first five sessions, the cardiovascular and subjective effects of single i.v. cocaine doses (0, 8, 16, 32 or 48 mg/70 kg) were determined. During the last three sessions, the effects of i.v. cocaine (0, 8 or 32 mg/70 kg) administered 4 times per session at 14-min intervals were determined. Single and repeated doses of cocaine produced dose-dependent increases in cardiovascular effects (e.g., diastolic pressure and heart rate), subjective effects (e.g., ratings of "High," or "Stimulated") and ratings of cocaine dose (e.g., "Quality," or "Liking"), regardless of methadone dose or the timing of cocaine administration. Increases in blood pressure after single cocaine doses were greater when cocaine was given 1 hr after methadone. Subjects maintained on higher methadone doses (> 60 mg) reported larger cocaine effects after single doses on several measures including ratings of Liking and Stimulated. Finally, the opiate symptom scores after cocaine administration were 100% larger than those observed previously after cocaine administration to opiate-experienced, but not dependent, individuals. These data suggest that any improvement in cocaine abuse observed in methadone-maintained individuals is not related to a blocking of the subjective effects of cocaine, and that higher methadone doses could have a negative impact on cocaine abuse in some individuals.

Adult↗
PubMed1994

Serum levels of soluble intercellular adhesion molecule 1 are increased in chronic B-lymphocytic leukemia and correlate with clinical stage and prognostic markers.

The serum levels of soluble intercellular adhesion molecule 1 (ICAM-1) were significantly elevated (P < .001) in patients with chronic B-lymphocytic leukemia (B-CLL, n = 113) compared with healthy controls (n = 31). sICAM-1 levels in B-CLL were positively correlated to the tumor mass as reflected by the modified Rai and the Binet staging systems, lymphocyte counts, and isolated spleno/hepatomegaly. During disease progression or regression on cytoreductive therapy, the circulating sICAM-1 levels changed accordingly. sICAM-1 was also correlated to a kinetic parameter such as the lymphocyte doubling time. Furthermore, the serum sICAM-1 levels were inversely correlated to hemoglobin levels in patients with early clinical stage, and this may turn out to be of prognostic value. sICAM-1 was compared with other serum markers said to reflect disease activity in B-CLL, ie, soluble CD23, thymidine kinase, lactate dehydrogenase (LDH), and beta 2-microglobulin. sICAM-1 was equally well or better correlated to clinical stage and lymphocyte doubling time. In univariate regression analysis, all serum markers but LDH correlated with survival, and in multivariate analysis, sICAM-1 was the only marker approaching significance for additional prognostic information when included after clinical stage and lymphocyte doubling time. Based on the present observations, it appears that prospective studies repeatedly monitoring serum sICAM-1 in B-CLL are justified.

Adult↗
PubMed1994

In vitro drug sensitivity testing of tumor cells from patients with non-Hodgkin's lymphoma using the fluorometric microculture cytotoxicity assay.

BACKGROUND: Tumor cell drug sensitivity is an important determinant of chemotherapy response. Its measurement in vitro would aid in therapy individualization and new drug development. MATERIALS AND METHODS: The fluorometric microculture cytotoxicity assay (FMCA), based on production by viable cells of fluorescent fluorescein after 3 days of culture, was used for cytotoxic drug sensitivity testing of 73 samples of tumor cells from patients with non-Hodgkin's lymphoma (NHL). RESULTS: The technical success rate was 92%, and FMCA data showed good correlation to the Disc assay. NHL samples were considerably more drug sensitive than were samples from in vivo resistant tumors. There was no obvious difference in drug sensitivity for high- vs. low-grade or untreated vs. previously treated low-grade NHL. For 26 patients, clinical outcome was correlated to in vitro response giving a sensitivity and specificity of 93 and 48%, respectively. Cross-resistance between standard drugs was frequent in vitro. Resistance modulators potentiated the effect of vincristine and doxorubicin in 10-29% of the samples, most frequently from previously treated patients. CONCLUSIONS: The FMCA seems to report clinically relevant drug sensitivity data for NHL, and thus it could serve as a tool for optimization of chemotherapy in the future.

Cell Survival↗
PubMed1993

Structure and function of proteins of the phosphotransferase system and of 6-phospho-beta-glycosidases in gram-positive bacteria.

New information about the proteins of the phosphotransferase system (PTS) and of phosphoglycosidases of homofermentative lactic acid bacteria and related species is presented. Tertiary structures were elucidated from soluble PTS components. They help to understand regulatory processes and PTS function in lactic acid bacteria. A tertiary structure of a membrane-bound enzyme II is still not available, but expression of Gram-positive genes encoding enzymes II can be achieved in Escherichia coli and enables the development of effective isolation procedures which are necessary for crystallization experiments. Considerable progress was made in analysing the functions of structural genes which are in close vicinity of the genes encoding the sugar-specific PTS components, such as the genes encoding the tagatose-6-P pathway and the 6-phospho-beta-glycosidases. These phosphoglycosidases belong to a subfamily of the beta-glycosidase family I among about 300 different glycosidases. The active site nucleophile was recently identified to be Glu 358 in Agrobacterium beta-glucosidase. This corresponds to Glu 375 in staphylococcal and lactococcal 6-phospho-beta-galactosidase. This enzyme is inactivated by mutating Glu 375 to Gln. Diffracting crystals of the lactococcal 6-P-beta-galactosidase allow the elucidation of its tertiary structure which helps to derive the structures for the entire glycosidase family 1. In addition, a fusion protein with 6-phospho-beta-galactosidase and staphylococcal protein A was constructed.

Amino Acid Sequence↗
PubMed1989

[Enzyme diagnosis of acute myocardial infarction].

During the past decade, determinations of enzyme concentrations in the blood in patients admitted with suspected acute myocardial infarction has been of increasing significance not only for early elucidation but also for establishing the correct diagnosis. This is partly the result of methods which can demonstrate the presence of myocardium-related isoenzymes and also because of the physiological basis for the release of enzymes and their metabolism bas been elucidated. In the present report, guidelines for clinical employment of enzyme investigations in acute myocardial infarction are presented. By means of blood sampling twice or thrice within a time interval af approximately 8-24 hours after the presumed time of infarction and determination of a limited number of enzymes in these samples, it is possible to exclude or confirm the presence of an infarct with high probability.

Humans↗
PubMed1988

CHOP versus prednisolone + chlorambucil in chronic lymphocytic leukemia (CLL): preliminary results of a randomized multicenter study.

Five hundred and fifty consecutive patients with newly diagnosed B-CLL have been registered and classified in a Danish multicenter study. The study includes a protocol for primary treatment of patients in stage B or C (at diagnosis or after demonstrated progression), below 76 years of age, and without complicating serious disease. Until now 144 such patients have been randomized to either prednisolone (PRD) plus chlorambucil (CLB) 5 days every 4 weeks or monthly intensive CHOP treatment. Twenty-nine percent of the treated patients achieved CR on PRD + CLB versus 63% on CHOP (p less than 0.005). No response was found in 29% versus 18%, respectively (NS). A significant difference in survival between patients achieving CR, PR and NR was also demonstrated, whereas to date no difference in survival could be demonstrated between the two regimens. The toxicity was limited, and only 2 treatment-related deaths occurred in approximately 700 CHOP treatment series.

Adult↗
PubMed1981

Oral glucose tolerance, insulin and gastric inhibitory polypeptide secretion in patients recovered from acute myocardial infarction.

Ten male patients, recovered from acute myocardial infarction, and ten control subjects were investigated by a 50 g glucose tolerance test. All patients and control subjects had normal glucose tolerance, but the patients had increased fasting and integrated insulin response to oral glucose. Fasting gastric inhibitory polypeptide concentrations and integrated gastric inhibitory polypeptide response were normal in the patients. The exaggerated insulin secretion in patients recovered from myocardial infarction does not seem to be caused by increased secretion of gastric inhibitory polypeptide.

Adult↗