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Biomedical subjects

B Ljungberg

Publications and source records attributed to B Ljungberg.

At least 73 records · Page 4Linked to original sources
PubMed1995

Serum acute phase reactants and prognosis in renal cell carcinoma.

BACKGROUND: Inflammatory parameters as acute phase proteins commonly are elevated in patients with renal cell carcinoma. Some of these acute phase reactants have been proposed to influence survival. METHODS: In 170 patients with renal cell carcinoma, the authors studied six acute phase reactant parameters (erythrocyte sedimentation rate [ESR], C-reactive protein, haptoglobin, ferritin, orosomucoid, and alpha 1-antitrypsin) that were compared with stage and grade. RESULTS: The acute phase reactants correlated well with each other and with stage and grade. All acute phase reactants separately were found to be significant prognostic factors of survival using the log rank test. However, when a multivariate Cox analysis was performed, only stage, grade, and ESR were identified as independent prognostic factors, whereas the other factors were not. CONCLUSIONS: The study suggests that all acute phase reactants separately were found to be significant univariate prognostic factors, but in a multivariate analysis, ESR was the only independent prognostic parameter for survival.

Acute-Phase Proteins↗
PubMed1995

A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. METHODS: We performed a multicenter trial comparing six weeks of oral anticoagulant treatment with six months of such therapy in patients who had a first episode of venous thromboembolism. Anticoagulant therapy consisted of warfarin or dicumarol. Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy. The initial diagnoses were confirmed by means of venography in cases of deep-vein thromboses (n = 790) and with perfusion-ventilation scanning or angiography in cases of pulmonary embolism (n = 107); recurrences were confirmed in the same way. RESULTS: After two years of follow-up, there had been 123 recurrences of venous thromboembolism that met the diagnostic criteria, 80 in the six-week group (18.1 percent; 95 percent confidence interval, 14.5 to 21.6) and 43 in the six-month group (9.5 percent; 95 percent confidence interval, 6.8 to 12.2). The odds ratio for recurrence in the six-week group was 2.1 (95 percent confidence interval, 1.4 to 3.1). There was no difference in mortality or the rate of major hemorrhage between the six-week and six-month groups. CONCLUSIONS: Six months of prophylactic oral anticoagulation after a first episode of venous thromboembolism led to a lower recurrence rate than did treatment lasting for six weeks. The difference between the two groups occurred between 6 weeks and 6 months after the start of treatment, and the rates of recurrence remained nearly parallel for 1 1/2 years thereafter.

Anticoagulants↗
PubMed1995

Vein invasion in renal cell carcinoma: impact on metastatic behavior and survival.

PURPOSE: The development of a thrombus extending into the veins is well recognized in renal cell carcinoma. We investigated the hypothesis that vein invasion alone has no adverse impact on survival but is a highly negative factor in other tumors. MATERIALS AND METHODS: In 200 consecutive patients invasion of the renal vein and vena cava was evaluated and compared with the clinical course. RESULTS: A total of 26 patients had vena caval and 47 had renal vein invasion. Patients with venous invasion had a significantly shorter survival but no survival difference was demonstrated based on the level of involvement. CONCLUSIONS: Our study indicates that vein invasion itself seems to be an important prognostic factor in renal cell carcinoma.

Adult↗
PubMed1995

Accuracy of clinical staging in non-seminomatous testicular cancer--a single centre experience of retroperitoneal lymph node dissection.

The management of low stage non-seminomatous testicular cancer remains a controversial issue. Programs of surveillance or primary retroperitoneal lymph node dissection (RPLND) after orchiectomy show equally good survival rates. Current focus is therefore on reduction of toxicity or side effects of the treatment while maintaining maximal prognostic safety. The clinician's decision of therapy is based on clinical staging methods including computerized tomography, pulmonary x-rays and serum tumour marker levels. In this study, the accuracy of clinical staging was compared with histopathology in 64 patients with clinical stages (CS) I and IIa, operated upon with RPLND between 1980 and 1992. Lymph node metastases were histopathologically verified in 37% of CS I and in 47% of CS IIa tumours. Thus, the clinical staging was inaccurate in 37% in CS I and in 53% in CS IIa patients. No clear relationship was shown between the risk factors: vascular invasion and/or tumour marker levels and metastatic spread. The specificity of clinical staging in non seminomatous testicular cancer was low. RPLND, on the other hand, is a reliable method for assessment of metastatic spread and will minimise unnecessary use of chemotherapy. Modern techniques for lymphadenectomy have a very low rate of post-operative morbidity. Development of better non-invasive imaging techniques for detection of lymph node metastases is hoped for, in order to improve the information on tumour spread and make it possible to individualize therapy. Thus, unnecessary therapy and following side-effects can be avoided, improving the patient's quality of life during and after treatment.

Biomarkers, Tumor↗
PubMed1994

Telomere shortening in renal cell carcinoma.

The ends of human chromosomes consist of a specialized structure, the telomere, composed of repeats of TTAGGG making up a total of 5-15 kilobase pairs, depending on age and proliferative activity of the tissue. The major function of telomeres is to provide stability to chromosomes and protect underlying unique coding sequences from degradation. There is a loss of telomeric sequences following every cell division estimated to be between 50 and 65 basepairs/cell division in human fibroblasts and embryonic kidney cells in vitro. This loss is due to the fact that DNA replication is incomplete for one strand at each telomere end. In lower eukaryotes there is a compensation mechanism provided by the enzyme telomerase, which is inactive in human somatic cells. Telomerase activation has also been detected in vitro immortalized human cells. In this study we analyzed renal cell carcinoma for the occurrence of telomere shortening using the probe (TTAGGG)4. Southern blots of HinfI-digested DNA revealed a shortening of mean telomere restriction fragment (TRF) length of 0.4 to 2.5 kilobase pairs in 2 or 3 intratumoral samples in all 10 tumors analyzed. No obvious intratumoral heterogeneity was found in mean TRF length values. However, heterogeneity was shown by the occurrence of at least two separate peak TRF values in 7 of 10 tumors, indicating the presence of different tumor cell clones. A conflicting observation was made when we evaluated the intensity of the hybridization signals, where three of the tumors showed an increase in hybridization signals despite concomitant TRF reduction. We found no correlation between tumor size and calculated tumor cell divisions undergone. In two tumors, the calculated cell division cycles were unrealistically low compared to the tumor size. These data suggest that telomerase activation might occur in human renal cell carcinoma.

Base Sequence↗
PubMed1994

Epidermal growth factor receptor gene expression and binding capacity in renal cell carcinoma, in relation to tumor stage, grade and DNA ploidy.

Epidermal growth factor receptor (EGFr) was studied in 19 renal cell carcinomas using competitive binding analysis and solution hybridization assay. EGFr binding capacity and EGFr mRNA expression were significantly higher in tumors in comparison with kidney cortex tissues. The EGFr binding capacity was higher in diploid than in aneuploid tumors. No differences in binding capacities or mRNA expression between different tumor grades or stages were demonstrated. It was concluded that EGFr is overexpressed in renal cell carcinoma, although with no relationship to tumor characteristics.

Adult↗
PubMed1994

Cell kinetics of renal cell carcinoma studied with in vivo iododeoxyuridine incorporation and flow cytometry.

In 29 patients with renal cell carcinoma tumor cell kinetics were studied by in vivo labeling with 100 mg. iododeoxyuridine given 3 to 7 hours before nephrectomy. Two to 6 samples were analyzed from each tumor after fixation in ethanol. Iododeoxyuridine was analyzed by specific antibodies using flow cytometric analysis of labeled cells and parameters, such as labeling index and potential tumor doubling time, could be determined. Samples from 28 tumors were evaluable. Mean labeling index of the tumors was 2.7%, which was significantly different from the 0.35% index in kidney cortex tissue. There was no statistical difference in labeling index among the clinical stages. The mean potential tumor doubling time in the tumor cells was 20.3 days, which was significantly different compared with 137.7 days in kidney cortex tissue. There was a frequent intra-tumoral heterogeneity of potential tumor doubling times. Diploid and aneuploid samples had significantly different potential tumor doubling (mean 37.4 and 12.5 days, respectively). Potential tumor doubling had a significant impact on the survival time (p = 0.004), which also was noted in the patients with aneuploid tumors (p = 0.003). Our study shows that in vivo incorporation of iododeoxyuridine successfully can be analyzed in renal cell carcinoma. Potential tumor doubling time gives valuable prognostic information on the clinical behavior of the patients.

Adult↗
PubMed1994

Levels of cadmium, zinc and copper in renal cell carcinoma and normal kidney.

Levels (microgram/g dry weight) of cadmium (Cd), zinc (Zn) and copper (Cu) were determined in kidneys with renal cell carcinoma from 20 male and 11 female patients. Autopsied kidneys from nine males and eight females who had died of nonmalignant diseases were used as controls. The mean levels in cortex of Cd was in cases 103.2 and in controls 79.9 (not significantly different). For non-smoking cases, mean level of Cd in cortex was somewhat lower than in the controls. No significant differences were found between cases and controls for Cd levels in the medulla. Zn in cortex was significantly lower in the cases aged > or = 69 years (mean 182.0) than in the corresponding controls (mean 237.6). Zn in medulla was significantly lower in all cases (mean 103.5) than in controls (mean 162.2). The mean level of Cu in the medulla in cases was 10.7 and in controls 13.0 (P = 0.05). No differences were found for Cu levels in cortex.

Aged↗
PubMed1994

Proliferation of human renal cell carcinoma studied with in vivo iododeoxyuridine labelling and immunohistochemistry.

Tumor cell proliferation is one interesting cell biological parameter of possible predictive value for prognosis. In the present study 176 tumor and 33 kidney cortex samples from 33 patients with renal cell carcinoma were studied after immunohistochemical detection of in vivo labelled iododeoxyuridine. The tumors had a mean labelling index (LI) of 1.06 +/- 0.59%, significantly different from LI of kidney cortex tissue 0.08 +/- 0.09% (p < 0.001). There was a tendency towards increasing LIs at higher clinical stages. No correlation was found between LI and tumor size. A significant difference existed for LIs between diploid and aneuploid tumors (p = 0.037). Within the limited number of patients with a relatively short follow-up, Kaplan-Meier curves indicated that LI might provide prognostic information.

Adult↗
PubMed1993

Tumor-cell proliferation and prognosis in renal-cell carcinoma.

In the present study the prognostic value of tumor S-phase fraction was evaluated in 69 patients with renal-cell carcinoma. The proportion of S-phase cells was calculated from DNA histograms by flow cytometry in multiple samples from each tumor. The mean tumor S-phase percentage varied between 1.0 and 17.0%, mean 7.5%, with a significant difference between diploid and non-diploid tumors. Stage-I tumors showed significantly lower S-phase values than tumors of stages II/III and IV. Histopathological grade correlated with fraction of cells in S-phase. Nineteen tumors were homogeneously diploid, I was tetraploid and 49 were aneuploid. Heterogeneity concerning S-phase values was found in 46 of the 69 tumors and concerning DNA ploidy in 34 tumors. Survival time was longer for patients with diploid tumors than for those with aneuploid tumors. Patients with S-phase values < 7.5% had a longer survival time than patients having tumors with S-phase values > 7.5%. Within the group of aneuploid tumors, patients with S-phase values < 7.5% had a significantly better prognosis. In multivariate analysis, only tumor stage and S-phase gave significant independent prognostic information. The S-phase fraction seems to be an additional prognostic parameter for patients with renal-cell carcinoma.

Adult↗
PubMed1993

Serum gamma-enolase and prognosis of patients with renal cell carcinoma.

BACKGROUND: Increased levels of gamma-enolase (gamma-enolase) have been observed in the sera of patients with renal cell carcinoma. To evaluate the prognostic information of gamma-enolase in this disease, 161 consecutive patients were assessed before initiation of therapy. METHODS: gamma-Enolase was analyzed in serum using an immunoradiometric assay. The patients were clinically staged and followed up for a median time of 36 months (range, 5-104 months). Actuarial survival was calculated using the Kaplan-Meier method. RESULTS: Elevated levels of gamma-enolase was found in 28 of 61 (46%) patients with distant metastases, compared with 8 of 56 (14%) when the tumor was confined to the kidney. A correlation also was observed between gamma-enolase and tumor grade, with poorly differentiated tumors having the highest levels. In 28 patients with distant metastases and elevated gamma-enolase, the survival time was significantly shorter than that of 31 patients with normal gamma-enolase levels (P < 0.001). The median survival time was 5 and 11 months, respectively. Using Cox proportional hazard model, clinical stage, serum gamma-enolase, and tumor grade were identified as independent prognostic factors. CONCLUSION: Serum gamma-enolase can be useful as an adjunct in the staging of renal cell carcinoma. It also gives predictive information and might be of value as a marker in adjuvant therapy.

Adult↗
PubMed1993

DNA fingerprinting of renal cell carcinoma with special reference to tumor heterogeneity.

Genomic alterations in renal cell carcinoma were investigated by DNA fingerprinting using the simple repetitive oligonucleotide probe (CAC)s. Nine of ten tumors showed somatic changes in the fingerprint pattern compared with constitutional DNA. The most consistent changes were deletions and/or decrease in intensity of a band. When using two or three samples from different parts within the tumor, up to three different cell clones could be detected. These results indicate that DNA fingerprinting analysis can be a useful technique for the study of genomic alterations and tumor heterogeneity in renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1993

The influence of dialyzer geometry on blood coagulation and biocompatibility.

The influence of dialyzer geometry on blood coagulation, heparin requirement and complement activation was studied in fourteen chronic hemodialysis patients. Each patient was dialyzed with two different cuprophan dialyzers, hollow fiber GF 120M and parallel plate Lundia IC5N. Both dialyzers had a wall thickness of 11 microns, surface area of 1.2 m2 and both were sterilized with ethylene oxide. Heparin doses were individually titrated. The mean heparin dose was 6089 +/- 988 U. Platelet count decreased from 218 x 10(9)/l to 193 x 10(9)/l and from 235 x 10(9)/l to 197 x 10(9)/l respectively (hollow fiber/plate dialyzer, ns). The number of leucocytes decreased at 15 min after start of dialysis by 56% and 61% (hollow fiber/plate dialyzer, ns). The heparin requirement, measured as prolongation of whole blood activated coagulation time after identical doses of heparin, were the same in hollow fiber and plate dialysis sessions. The arterial fibrinopeptide A concentrations increased during dialysis from 5.4 to 7.1 nmol/l and 8.5 to 9.6 nmol/l respectively (hollow fiber/plate dialyzer, ns). The residual blood volume in the hollow fiber dialyzers was 1.3 +/- 1.1 ml and in the plate dialyzers 1.5 +/- 0.9 ml (ns). C3a activation, indicated by a marked arterio-venous difference, was observed at 15 min after start of dialysis with hollow fiber as well as plate dialyzers. The arterio-venous difference was less pronounced at the end of dialysis. There were no differences in C3a activation between hollow fiber and plate dialyzers at any timepoint. It is concluded that dialyzer geometry does not significantly influence platelet count, blood coagulation, heparin requirement or complement activation.

Aged↗
PubMed1992

Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients.

The altered pharmacokinetic properties of, e.g., aminoglycosides in cystic fibrosis patients have to be considered when pulmonary exacerbations are treated. Since reported data on ciprofloxacin, a fluorinated quinolone, are conflicting, we compared intravenous and oral administration in cystic fibrosis patients when treating them for mild symptoms of pulmonary infection. All of the patients were colonized with Pseudomonas species. Ciprofloxacin was administered orally (15 mg/kg of body weight) or intravenously (6 mg/kg) twice a day for at least 10 days during separate treatment periods. Five healthy volunteers received single intravenous and oral doses. Pharmacokinetic evaluations were performed at first dose and at steady state. The results showed that cystic fibrosis patients have increased oral bioavailability of ciprofloxacin (80% in cystic fibrosis patients versus 57% in volunteers) and increased total clearance (688 ml/min in CF patients versus 528 ml/min in volunteers). Our data indicate that the pharmacokinetic properties of ciprofloxacin are altered in cystic fibrosis patients with mild symptoms of pulmonary exacerbations and that the changes most probably are due to cystic fibrosis per se or to the impact of chronic infection.

Administration, Oral↗
PubMed1992

Pharmacokinetics of meropenem and its metabolite in young and elderly healthy men.

The pharmacokinetics of meropenem and its ring-opened metabolite (ICI 213,689) were investigated with eight young (20- to 34-year-old) and eight elderly (67- to 80-year-old) healthy male volunteers given single 30-min intravenous infusions of 500 mg of meropenem. All subjects had normal age-correlated glomerular function. The mean terminal half-life of meropenem was 1.27 h in the elderly subjects versus 0.81 h in the younger subjects (P less than 0.001). This and similar increases in mean residence time and area under the concentration-time curve were explained by a reduction in total [139 versus 203 ml/(min.1.73 m2); P less than 0.001], renal, and nonrenal clearances in subjects at advanced ages. The apparent volume of distribution and urinary recovery over 8 h were not significantly altered. With the metabolite, prolonged serum half-life and mean residence time, enlarged area under the concentration-time curve, and lower renal clearance but no significant changes in peak plasma concentration or urinary recovery were found in the elderly. The reduction in the renal excretion rate of meropenem and its metabolite corresponds to the age-associated physiological decline in renal function. The capacity to metabolize meropenem may also be slightly impaired in people at advanced ages. Dose reduction of meropenem should be considered for elderly patients.

Adult↗
PubMed1992

Erythropoietin in renal cell carcinoma: evaluation of its usefulness as a tumor marker.

Erythropoietin levels in serum were analyzed in 165 patients with renal cell carcinoma. All samples were taken before therapy and stored at -80 degrees C. Erythropoietin, a glucoprotein produced by the renal cortex was quantified by an enzyme immunoassay. Fifty-five of 165 patients (33%) had elevated serum levels. In patients with metastatic disease (M+), elevated levels were found in 24 of 65 cases (38%). Patients with high-grade tumors had significantly more often increased erythropoietin than those with low-grade tumors. No correlation between erythrocytosis and elevation of erythropoietin in serum was found. There was a significant difference in survival between patients with normal and patients with elevated erythropoietin levels (p = 0.013). The study shows that erythropoietin is a tumor marker with a low sensitivity. However, it correlates with stage and grade and provides prognostic information.

Biomarkers, Tumor↗
PubMed1992

Efficacy and tolerance of roxithromycin in comparison with erythromycin stearate in patients with lower respiratory tract infections.

The efficacy and tolerance of roxithromycin 150 mg b.i.d. were compared with those of erythromycin stearate 500 mg b.i.d. in patients with lower respiratory tract infections. Out of 86 patients recruited for the study, 79 were evaluable for tolerance and 76 for efficacy. These patients were evenly distributed among the 3 investigational clinics, with 26, 25 and 28 patients, respectively. The diagnosis of lower respiratory tract infections was based on clinical, laboratory, radiological and/or physical findings and, when available, bacteriological and serological findings. The duration of treatment was 10 days, with follow-up at post-treatment visits directly after treatment and 6 weeks thereafter. The clinical outcome was satisfactory with no significant difference between the drugs. More patients reporting adverse events were on erythromycin than on roxithromycin (51.3% vs 17.5%; p = 0.003). The results suggest that roxithromycin is as effective as erythromycin stearate in the treatment of lower respiratory tract infections and causes fewer adverse effects.

Adult↗