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Biomedical subjects

B Ljungberg

Publications and source records attributed to B Ljungberg.

At least 19 recordsLinked to original sources
PubMed2006

Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.

BACKGROUND: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. METHODS: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.

Aged↗
PubMed2004

Expression of vascular endothelial growth factor protein in human renal cell carcinoma.

OBJECTIVE: To evaluate the effect of vascular endothelial growth factor (VEGF, one of the most important angiogenetic factors) in renal cell carcinoma (RCC) by analysing many RCCs for the expression of immunohistochemical (IHC) VEGF-staining related to clinicopathological findings and survival. PATIENTS AND METHODS: VEGF immunostaining was examined with the tissue microarray (TMA) method on tumour samples from 229 patients and validated in 71 by ordinary tissue sections (TS). IHC VEGF expression was quantified by estimating the volume density and staining intensity on a three-grade scale. RESULTS: In most RCCs there was VEGF staining in the cell cytoplasm and membrane. In cell membranes the VEGF expression declined with storage time. IHC VEGF expression analysed by TMA and TS gave corresponding results. There was no difference in VEGF expression among conventional, papillary and chromophobe RCCs. There were significant correlations between VEGF expression and tumour size and stage. In univariate analysis VEGF expression correlated with survival, especially in conventional RCCs; this prognostic information was lost in multivariate analysis. The VEGF staining intensity correlated only with VEGF expression but not with any clinicopathological factors. CONCLUSIONS: VEGF protein was present in most RCC cells. There was no difference in VEGF expression among the different RCC types. The correlation between VEGF expression and tumour stage and with prognosis indicates the significance of VEGF within tumour growth and progression in RCC.

Adult↗
PubMed2004

Nephron-sparing surgery--strategies for partial nephrectomy in renal cell carcinoma.

The use of partial nephrectomy for renal cell carcinoma has continuously changed in the clinical practice. Previously it was mostly used in imperative cases, in patients with a solitary kidney or in patients with a risk of renal failure. An increased number of incidentally detected renal cell carcinomas are diagnosed due to the advances of the radiological methods. These tumours tend to be smaller and generally with a lower stage. The reported excellent results of partial nephrectomy have promoted the use of nephron-sparing surgery also in patients with a normal contralateral kidney and tumours smaller than 4-5 cm. The technical outcome is excellent with a low operative morbidity and a good oncologic control. Therefore partial nephrectomy has become a standard technique in the treatment of properly selected patients. Laparoscopy with its reduced postoperative pain and shorter rehabilitation time, has encouraged the interest in minimally invasive nephron sparing surgical techniques. Although low, the risk of local tumour recurrence and surgical complications are higher after nephron-sparing surgery compared with radical nephrectomy. Furthermore, long-term renal function remains adequate in most patients with a normally functioning contralateral kidney also after radical nephrectomy. Albeit these facts, there is convincing evidence justifying nephron-sparing surgery to be used routinely for patients with a small renal cell carcinoma and a normal functioning contralateral kidney.

Carcinoma, Renal Cell↗
PubMed2003

LRIG1 and epidermal growth factor receptor in renal cell carcinoma: a quantitative RT--PCR and immunohistochemical analysis.

In all, 31 renal cell carcinomas (RCCs) were examined for expression of the potential tumour suppressor LRIG1 (formerly Lig-1) and the epidermal growth factor receptor (EGFR). Eight matched samples of uninvolved kidney cortex were also evaluated. Gene expression was examined by quantitative real-time RT-PCR. In the eight matched sample pairs (uninvolved kidney cortex and tumour), protein expression was examined by immunohistochemistry. Conventional (clear cell) tumours showed an expected upregulation of EGFR. LRIG1 expression was generally downregulated in conventional and papillary RCC but not in chromophobic RCC. The ratio between EGFR and LRIG1 was more than 2.5-fold higher in the eight tumours compared with matched uninvolved kidney cortex and was at least two-fold higher than the mean normal ratio in 21 of 31 samples analysed. The observed downregulation of LRIG1 and increased EGFR/LRIG1 ratios are consistent with LRIG1 being a suppressor of oncogenesis in RCC by counteracting the tumour-promoting properties of EGFR. Further studies are justified to elucidate the explicit role of LRIG1 in the oncogenesis of RCC.

Adult↗
PubMed2003

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray.

Aberrations in the G1/S transition of the cell cycle have been observed in many malignancies and seem to be critical in the transformation process. Few studies have delineated the presence of G1/S regulatory defects and their clinical relevance in renal cell carcinoma (RCC). Therefore, we have examined the protein contents of cyclin D1, D3, E, and p27 in 218 RCCs, using tissue microarray and immunohistochemistry. The results from a subset of tumours were confirmed by Western blotting and immunohistochemical staining of regular tissue sections. Interestingly, low protein contents of cyclin D1 and p27 were associated with high nuclear grade, large tumour size, and poor prognosis for patients with conventional tumours. We further observed substantial differences in the pattern of G1/S regulatory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27; however, chromophobe tumours generally lacked p27 staining. In addition, conventional RCCs often expressed high cyclin D1 protein levels, while papillary RCCs exhibited high cyclin E. In summary, we have shown that G1/S regulatory defects are present in RCC and are associated with clinico-pathological parameters. The pattern of cell cycle regulatory defects also differed between RCC subtypes.

Actuarial Analysis↗
PubMed2002

The free beta-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma.

The free beta-subunit of human chorionic gonadotropin beta is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human chorionic gonadotropin beta expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin beta in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin beta in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin beta, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin beta were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin beta levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l(-1), P=0.0029). In multivariate analysis human chorionic gonadotropin beta, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin beta is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin beta in serum may be used to identify patents with increased risk of progressive disease.

Adult↗
PubMed2002

Prognostic importance of serum vascular endothelial growth factor in relation to platelet and leukocyte counts in human renal cell carcinoma.

It has been shown that both serum vascular endothelial growth factor (VEGF) and also platelet counts are associated with survival in renal cell carcinoma (RCC). It is not known, however, whether VEGF in serum relates to the angiogenic activity of the tumour or is derived from circulating blood components. Therefore, the interrelation between serum VEGF, platelet and leukocyte counts compared with health history, clinicopathological findings and outcome was evaluated in patients with RCC. Blood samples were collected before nephrectomy in 161 patients. Serum VEGF165 was assessed by a quantitative ELISA method. Platelet and leukocyte counts were analysed routinely and obtained from medical records. The variables were compared using univariate and multivariate analysis. There were significant correlations between VEGF levels, and platelet (P < 0.001) and leukocyte counts (P < 0.001). Serum VEGF levels, platelet counts, as well as leukocyte counts correlated significantly to stage and grade. Platelet counts were significantly lower in men with medication (P = 0.042), and decreased with age particularly in women (P = 0.001). Age or medication did not affect VEGF levels or leukocyte counts. Both VEGF and platelets gave significant prognostic information in univariate analysis. Using Cox multivariate analysis, VEGF was the last variable to be excluded. Only stage and grade remained as independent prognostic factors. Both VEGF levels and platelet counts gave prognostic information but VEGF was more reliable as predictor of survival in patients with RCC.

Adult↗
PubMed2002

Bactericidal effect of combinations of antibiotic and antineoplastic agents against Staphylococcus aureus and Escherichia coli.

BACKGROUND: The bactericidal effect of some antibiotic and antineoplastic agents commonly used in clinical practice was investigated to analyse whether the combinations act synergistically, have indifferent or antagonistic antibacterial effects compared to the effect of the antibiotics alone. METHODS: The rate of killing of meropenem, ceftazidime and tobramycin was studied against six different strains of Staphylococcus aureus and Escherichia coli, and the results were compared to the rate of killing of the antibiotics in combination with the cytostatic drugs doxorubicin, etoposide and 5-fluorouracil (5-FU). RESULTS: Tobramycin showed synergy against two strains of S. aureus after 3 h in the presence of 5-FU and against one strain of S. aureus in the presence of doxorubicin. Meropenem induced an antagonistic bactericidal effect against one isolate of S. aureus after 24 h. Ceftazidime expressed an indifferent bactericidal effect together with the cytostatic agents. The antineoplastic agents had no impact on the bacterial killing of any of the antibiotics against E. coli. CONCLUSIONS: Tobramycin expressed a significantly better bactericidal effect against S. aureus after 3 h in the presence of doxorubicin and 5-FU than tobramycin alone. Meropenem expressed antagonism against one clinical strain of S. aureus, but the cytostatic drugs did not affect the killing of other strains tested. Ceftazidime expressed indifferent bactericidal activity together with the antineoplastic agents.

Anti-Bacterial Agents↗
PubMed2002

Postantibiotic effect of meropenem and ciprofloxacin in the presence of 5-fluorouracil.

BACKGROUND: The postantibiotic effect (PAE) of meropenem and ciprofloxacin was studied in the presence of the antineoplastic agent 5-fluorouracil (5-FU). The purpose of the study was to investigate whether the PAEs of the combinations differed from the PAEs of the antibiotics alone. METHODS: The PAEs of the combinations of 5-FU plus meropenem or ciprofloxacin were determined with viable counts against four reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli and two clinical isolates of S. epidermidis. The results were compared with the PAEs of the antibiotics drugs and 5-FU alone. The gram-positive strains were tested for slime production, both alone and in the presence of 5-FU. RESULTS: Against two of the three tested strains of S. epidermidis, the combination of ciprofloxacin and 5-FU gave a synergistic prolongation of the PAE in comparison with the PAEs induced by the drugs alone. The combinations showed indifference against the other bacteria. The combination of meropenem and 5-FU had a synergistic PAE against one of the three tested strains of S. epidermidis and an additive effect against E. coli but showed indifference against the rest of the strains. CONCLUSIONS: The presence of 5-FU did not influence the PAEs of the antibiotics against most of the tested strains, but caused a synergistic prolongation of the PAEs induced by ciprofloxacin and meropenem against some of the tested strains of S. epidermidis. 5-FU inhibited slime production in the same S. epidermidis strains, which might have contributed to the longer PAE.

Anti-Infective Agents↗
PubMed2001

Similar rates of exponential decrease in serum concentrations of free prostate-specific antigen (PSA), PSA complexed to alpha-1-antichymotrypsin, and human glandular kallikrein 2 (hK2) in prostate cancer patients treated with GnRH-analogues.

BACKGROUND: Our recently reported finding of rapid bi-exponential elimination of free prostate-specific antigen (PSA) after radical retropubic prostatectomy in patients with moderately elevated PSA levels, which contrasted a very slow, linear elimination of PSA complexed to alpha-1-antichymotrypsin (ACT), prompted us to study whether these elimination rates were applicable for patients selected for castration treatment with very high pretreatment concentrations of PSA in serum. In addition, serum concentrations of hK2, the activator of proPSA, were measured. METHODS: Pretreatment serum was obtained from 21 previously untreated prostate cancer patients due for hormonal treatment with a GnRH-analog. Samples were also collected during treatment up to a minimum of 24 weeks at 2-week intervals and analyzed with immunofluorometric assays for free PSA (PSA-F), PSA complexed to alpha-1-antichymotrypsin (PSA-ACT), total PSA (PSA-T), and human kallikrein 2 (hK2). For pharmaco-kinetic analysis the serum concentrations of hK2 and PSA forms for each patient were plotted against time both before and after logarithmic transformation and the half-lives were calculated as ln2/k. RESULTS: Median pretreatment serum concentrations were 322 ng/ml (range, 1.9-2210) for PSA-T, 27.8 ng/ml (range, 1.14-259) for PSA-F, and 207 ng/ml (range, 0.8-2080) for PSA-ACT. All patients had castrate levels of serum testosterone (< 2.5 nmol/l) in less than 21 days after initiation of GnRH-analog treatment. It was possible to evaluate data from 19/21 patients which showed an exponential decrease of all PSA concentrations in serum, with mean half-lives of 12.9 days (range, 7.3-30) for PSA-T, 15.5 days (range, 7.7-37.5) for PSA-F, and 12.3 days (range, 6.6-30) for PSA-ACT. Median pretreatment percent free PSA (PSA-F/PSA-T) was 12% compared to 18% at nadir. The median pretreatment level of hK2 was 3.5 ng/ml (range, 0.29-30.3). There was an exponential decrease in hK2 concentrations in serum after initiation of hormonal treatment with a mean half-life of 18.7 days (range, 7.5-37.5). CONCLUSIONS: For the majority of patients with hormonally treated prostate cancer the serum concentrations of PSA-T, PSA-F, PSA-ACT, and hK2 decreased slowly in parallel and mono-exponentially after initiation of treatment. Mean half-lives were between 12 and 19 days.

Aged↗
PubMed2001

Impact of serum basic fibroblast growth factor on prognosis in human renal cell carcinoma.

Renal cell carcinoma is often characterised by extensive vascularity and angiogenic factors may be of importance for disease progression. Using a sandwich enzyme immunoassay, basic fibroblast growth factor (bFGF) was analysed in the sera from 206 patients with renal cell carcinoma before the initiation of therapy. The median bFGF level was 3.0 pg/ml (range <1.0-70.9 pg/ml). The serum levels were significantly correlated to tumour stage and nuclear grade. Patients with tumour thrombus to the renal or the inferior caval vein had significantly higher serum bFGF levels compared with those with non-invading tumours (P=0.007). Patients with serum bFGF levels above 3.0 pg/ml had a worse prognosis, compared with those with lower levels (P=0.001). Furthermore, patients with tumours with vein invasion had a worse prognosis compared with those without invasion. After multivariate analysis, only tumour stage and grade remained as independent prognostic factors.

Adult↗
PubMed2001

Pharmacokinetics of ceftazidime in febrile neutropenic patients.

Eight patients with fever and neutropenia were given 2 g of ceftazidime i.v. as a bolus injection over the course of 3 min. The pharmacokinetic variables for ceftazidime were similar to those found previously in febrile, acutely ill, non-neutropenic patients. The area under the plasma-concentration-time curve was significantly smaller, and the terminal half-life (t1/2lambda(z)) significantly shorter, compared with elderly, healthy subjects (p < 0.005). Three patients survived long enough to be assayed after normalization of temperature and neutrophil counts. Glomerular filtration rates and clearances tended to be higher and the area under the curve and half-life lower on the day of fever and neutropenia. When considering our data in relation to known MIC values for common pathogens, ceftazidime administered intermittently every 6 h seems an appropriate regimen in patients with febrile neutropenia. Larger studies are needed to confirm this.

Adult↗
PubMed2001

p53 expression in correlation to clinical outcome in patients with renal cell carcinoma.

OBJECTIVE: The aim of this study was to evaluate the role of p53 as prognostic factor in renal cell carcinoma (RCC) and its relation to clinicopathological factors. MATERIAL AND METHODS: The nuclear accumulation of p53 protein was determined by immunohistochemical analysis in RCC specimens from 90 patients and was correlated with clinical stage, grade, DNA ploidy, S-phase fraction and cancer-specific survival. RESULTS: p53 overexpression was observed in 17 of 90 (19%) tumours. There was a significant correlation to stage (p = 0.016) and grade (p = 0.020) but not to DNA ploidy or S-phase. Patients with high p53 immunoreactivity had shorter cancer-specific survival (p = 0.003) than those with normal p53 protein expression. This difference was found in papillary and chromophobe tumour types (p < 0.0001) but not in conventional RCC. CONCLUSIONS: In patients with RCC, significant correlations between p53 protein expression and tumour stage, grade and survival time were observed. For patients with chromophobe and papillary tumour types, but not in conventional RCC, p53 immunoreactivity gave prognostic information, suggesting that the prognostic differences in p53 immunoreactivity might be due to disparate genetic abnormalities in the different RCC types.

Adult↗
PubMed2001

Diagnosis of renal cell carcinoma by bone marrow aspiration biopsy.

We report a patient who presented with persistent unclear fever, anaemia and leucopenia. A bone marrow aspiration biopsy was performed due to these symptoms, revealing malignant adenocarcinoma cells with a suspicion of renal origin. A computerized tomography confirmed the diagnosis. The patient progressed rapidly and died of widespread metastatic papillary renal cell carcinoma.

Biopsy, Needle↗
PubMed2001

Increased serum cortisol levels are associated with high tumour grade in patients with renal cell carcinoma.

Cortisol and dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) are the major steroid hormones produced by the human adrenal cortex. The serum levels of cortisol and DHEAS were analysed in 211 consecutive patients with renal cell carcinoma before initiation of therapy. Serum cortisol was significantly higher in patients with renal cell carcinoma compared with that in patients with benign cysts (p < 0.0001). Serum cortisol was independent of disease stage, but positively correlated to tumour diameter and grade. The serum levels of DHEAS were higher in men than in women, and decreased with age, but did not correlate with disease stage, tumour diameter or grade. The prognosis of patients with elevated serum cortisol tended to be poorer (p = 0.06) than the prognosis of those with lower levels. In a multivariate analysis, disease stage and tumour grade were independent predictors of prognosis. Age, gender and serum levels of cortisol and DHEAS were of limited value for prognosis.

Adult↗
PubMed2001

Tumor associated trypsin inhibitor as a prognostic factor in renal cell carcinoma.

PURPOSE: We analyzed the prognostic significance of pretreatment serum tumor associated trypsin inhibitor in renal cell carcinoma. MATERIALS AND METHODS: Serum samples were obtained before surgery from 188 patients who underwent radical nephrectomy for renal cell carcinoma. Median followup of living patients was 8.5 years. Serum tumor associated trypsin inhibitor was measured by a time resolved immunofluorometric assay. Statistical analysis was performed using the Kaplan-Meier method, log rank and stratified log rank tests. RESULTS: Preoperatively serum tumor associated trypsin inhibitor was elevated with a cutoff 16 microg/l in 48% of the patients with normal serum creatinine. The concentration in patients with cancer was significantly higher than in controls (p <0.0001). The serum level correlated with clinical stage and nuclear grade. Patients with an elevated level had significantly shorter survival time than those with a normal level (p = 0.005). Stratified log rank test demonstrated that tumor associated trypsin inhibitor was a prognostic factor independent of stage and grade in all patients as well as in those with nonmetastatic disease. CONCLUSIONS: Increased preoperative serum tumor associated trypsin inhibitor was associated with poor survival in renal cell carcinoma. The serum level was an independent prognostic variable. Preoperative serum tumor associated trypsin inhibitor appears to be a useful predictive factor that may be used to identify patients at increased risk of aggressive disease.

Adult↗