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Biomedical subjects

B Ljungberg

Publications and source records attributed to B Ljungberg.

At least 55 records · Page 3Linked to original sources

Renal mobility in a clinical patient material submitted for urography.

The clinical entity of increased renal mobility accompanied by typical clinical symptoms is usually referred to as mobile kidney. The renal mobility in a normal population has never been established. The aim of this study was to determine the mobility range of both kidneys, and to evaluate the limits of increased renal mobility and its frequency in a population without symptoms of mobile kidney. In a prospective study, 131 patients referred for urography were examined in the supine and erect positions and the mobility of each kidney was measured on the films. Mobility expressed in lumbar vertebral heights varied from 0 to 2.75 for the right kidney and from 0 to 2.0 for the left kidney. The renal mobility was greater among women than among men, and the degree of renal mobility was significantly correlated to low weight and, among women, also to height. An increased renal mobility was defined as mean + 2 SD. Based on the data from the study population the limit for increased renal mobility was found to be 2.0 vertebral body heights on the right side and 1.75 vertebral body heights on the left side. The frequency of increased renal mobility in the population was 7%. Increased renal mobility was significantly more frequent among women (13%), and on the right side. In conclusion, the renal mobility varied widely and increased renal mobility was frequent in patients without symptoms related to the renal mobility.

Adolescent↗

Radical nephrectomy is still preferable in the treatment of localized renal cell carcinoma. A long-term follow-up study.

OBJECTIVES: Due to the advances of radiological methods, an increased number of incidentally detected renal cell carcinomas is diagnosed. The reported excellent results of nephron-sparing surgery have promoted its application in patients with a normal contralateral kidney. However, the risk of local tumor recurrence and surgical complications after nephron-sparing surgery might be higher compared with radical nephrectomy. METHODS: In 89 patients with localized renal cell carcinoma treated with radical nephrectomy, long-term renal function, morbidity, and survival were evaluated. The renal function was followed up regularly with serum creatinine measurements. RESULTS: The cause-specific 5-year survival rate was 91.6%. There was neither local nor contralateral kidney tumor recurrence in any patient. Surgical complications were observed in 3% of the patients. Mean serum creatinine after the nephrectomy was 123 mumol/l without further increase during 10 years of follow-up. CONCLUSIONS: Radical nephrectomy of localized renal cell carcinoma has low morbidity, excellent local tumor control, and a high survival rate. For patients with a normally functioning contralateral kidney the long-term renal function remained adequate. Based on these data, there is no convincing evidence justifying nephron-sparing surgery to be used routinely for patients with a normally functioning contralateral kidney.

Adult↗

Loss of heterozygosity at chromosome 3p correlates with telomerase activity in renal cell carcinoma.

Acquired loss of the entire or parts of the short arm of chromosome 3 is a frequent aberration in renal cell carcinoma as well as in other tumour types, indicating the presence of at least one tumour suppressor gene on 3p. Previous studies have defined the distal and proximal ends of one critical region to reside between 3p21 and 3p11, and one gene involved in von Hippel-Lindau disease has been identified at 3p25. Experimental in vitro data has suggested a negative regulator of telomerase activity on chromosome 3. In the present study we investigated the relationship between telomerase activity and loss of heterozygosity (LOH) on 3p in a series of renal cell carcinomas. Telomerase activity was evaluated using the telomeric repeat amplification protocol assay and LOH, by analysis of 17 polymorphic microsatellite markers. Twenty-nine out of 45 tumours (64%) demonstrated telomerase activity and 37 tumours (82%) showed allelic loss of single or multiple areas of chromosome 3p. A significant correlation between LOH of at least one of three markers localised within 4 cM in the region of 3p21.2-3p14.2 and telomerase activity was demonstrated (p=0.0031), as well as for three distal markers within 3 cM at 3p24.3-3p24.1 (p=0.0287). These data suggest the presence of at least two genes with regulatory function on the expression of telomerase. These genes can encode proteins of importance for senescence and/or immortalisation or have a more direct effect on activation of telomerase.

Carcinoma, Renal Cell↗

Evaluation of five glycoprotein tumour markers (CEA, CA-50, CA-19-9, CA-125, CA-15-3) for the prognosis of renal-cell carcinoma.

Increased levels of glycoprotein tumour markers have been observed in sera of patients with renal-cell carcinoma. Five different glycoprotein markers [carcinoembryonic antigen (CEA), CA-50, CA-19-9, CA-125 and CA-15-3] were assessed in 154 consecutive patients with renal-cell carcinoma before initiation of therapy. To evaluate their prognostic information, the serum tumour markers were compared with tumour stage and grade. Actuarial survival was calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed to determine the prognostic significance of the markers. Elevated serum levels were found for all markers tested except for CEA. For CA-125 and for CA-15-3, elevated serum levels were correlated to clinical stage and tumour grade. For patients with elevated CA-125, survival time was significantly shorter than for patients with normal CA-125 levels. Using the Cox proportional-hazard model, we identified clinical stage, tumour grade and serum CA-125 as independent prognostic factors. Serum CA-125 and CA-15-3 may be useful as an adjunct in the staging of renal-cell carcinoma. CA-125 also gives prognostic information and might be of predictive value in renal-cell carcinoma.

Adult↗

The Heidelberg classification of renal cell tumours.

This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996. The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys. The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities. Benign tumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma. Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified. This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice.

Humans↗

Pharmacokinetics of meropenem in febrile neutropenic patients. Swedish study group.

To determine the impact of neutropenia on the pharmacokinetics of meropenem, 14 patients with fever and neutropenia were given 1 g of meropenem i.v. every 8 h as an infusion over 30 min. The volume of distribution (16.2 l/1.73 m2) and the nonrenal clearance [75 ml/(min x 1.73 m2)] in this group were significantly increased compared to healthy subjects studied previously with identical techniques. The kinetic study was repeated when the patients had a normal temperature and a raised neutrophil count; most kinetic variables did not differ from the findings on the first day of treatment. The pharmacokinetic profile of meropenem in febrile neutropenic patients differs from earlier findings in healthy subjects. Considering these data and known minimum inhibitory concentration values for common pathogens, meropenem administered every 6 to 8 h seems an appropriate regimen in patients with febrile neutropenia. The shorter time interval may be used for treatment of Pseudomonas infection.

Adult↗

Serum interleukin-6 in relation to acute-phase reactants and survival in patients with renal cell carcinoma.

Patients with malignancies often present with signs of inflammatory reactions such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Since interleukin-6 (IL-6) is a possible regulator of these reactions and has been proposed as a predictor of prognosis, the aim of the study was to analyse its clinical significance in patients with renal cell carcinoma. Serum samples were collected from 196 patients before any treatment. IL-6 was analysed by an enzyme-linked immunoassay and compared with tumour grade, stage, acute-phase reactants and survival. Patients with renal cell carcinoma had significantly higher IL-6 levels (mean 28.1 +/- 63.4 ng/l; median 8.3 ng/l) compared with controls (mean 1.7 +/- 2.6 ng/l; median 0.5 ng/l; P < 0.001). Serum IL-6 levels in patients with distant metastases were significantly higher than for patients with tumours confined to the kidney (P = 0.02). This difference was more pronounced when serum IL-6 levels in patients with poorly differentiated tumours were compared with well-differentiated tumours (P < 0.001). A significant correlation between the acute-phase reactants CRP, ESR and IL-6 levels was found. Survival time was significantly shorter (P = 0.001) for patients with IL-6 levels above the median serum level compared with patients with lower levels. Similar significant prognostic results were obtained in the group of patients with metastatic disease, but not in group of patients with stage I-III. Serum levels of IL-6 correlated to tumour stage, grade and acute-phase reactants. Increased levels were related to the presence of metastases and adverse survival. Serum IL-6 proved univariate prognostic information but this prognostic significance was lost using a multivariate analysis.

Acute-Phase Reaction↗

Soluble ectodomain of c-erbB-2 oncoprotein in relation to tumour stage and grade in human renal cell carcinoma.

The soluble ectodomain of c-erbB-2 oncoprotein was measured using a sandwich enzyme immunoassay in sera from 184 patients with renal cell carcinoma before initiation of treatment. The median serum level was 2062 U ml(-1) (range 865-4905 U ml(-1)). Levels were unaffected by sex, age and renal function. An inverse relation between disease stage (P = 0.0017) and tumour grade (P = 0.0009) and the serum level of c-erbB-2 ectodomain was observed. Survival time for patients with serum levels above median level was significantly longer than for patients with lower levels (P = 0.003). In a multivariate analysis, c-erbB-2 oncoprotein lost its prognostic information, while tumour stage and tumour grade were identified as independent prognostic factors.

Adult↗

Cellular changes in prostatic carcinoma after treatment with orchidectomy, estramustine phosphate and medroxyprogesterone acetate.

Thirty-three patients with prostatic carcinoma were treated with either estramustine phosphate, orchidectomy or high dose medroxyprogesterone acetate. Therapy response was evaluated by cytological examination of fine needle aspiration biopsies performed before and after 6 weeks treatment. At follow-up, 11 of 14 patients treated with estramustine phosphate had regressive and/or degenerative changes, in 2 patients there were no prostatic carcinoma cells in the smears and in one there was a marked reduction of the number of tumour cells. In 7 of 10 patients treated with orchidectomy there was a marked reduction of the percentage of malignant cells while smears from 3 patients were unchanged. In the 8 patients treated with high dose medroxyprogesterone acetate the cell patterns were unmodified compared with before treatment. We conclude that, in contrast to the lack of effect of treatment with medroxyprogesterone acetate, treatment with orchidectomy and especially estramustine phosphate caused morphologic cellular changes in prostatic carcinoma.

Aged↗

Specific genetic changes of diagnostic importance in chromophobe renal cell carcinomas.

The histologic diagnosis of chromophobe renal cell carcinomas is often uncertain because of phenotype overlap among different types of kidney cancers. Recently, in a novel genetic classification of renal cell tumors, a combination of monosomies of chromosomes 1, 2, 3, 6, 10, 13, 17, and 21 have been suggested to have a diagnostic value for this unique type of tumor. Therefore, we have analyzed fresh and paraffin-embedded tissues obtained from 42 chromophobe renal cell carcinomas for allelic losses at the above-mentioned chromosomal regions by employing microsatellite markers. Loss of chromosomes 1, 2, 6, 10, 13, and 17 was detected in between 75% and 95% of tumors, and loss of chromosome 21 was observed in 54% of cases. All but one tumor showed a combination of monosomies at the specific chromosomes. Thus, applying the set of microsatellite markers used in this study, a PCR-based diagnosis of chromophobe renal cell carcinomas could be established within 1 to 2 days. The general applicability of this approach to fresh and paraffin-embedded tissues allows a correct genetic characterization in all cases where a diagnosis based on histopathology remains uncertain.

Alleles↗

Telomerase activity in human renal cell carcinoma.

Telomeres have a vital role in maintaining chromosome stability and are essential for long term viability. Since the very ends of linear chromosomes cannot replicate, telomeres shorten in normal somatic cells eventually resulting in growth inhibition. However, most immortal cell lines maintain stable telomeres indicating that mechanisms exist to compensate for the end replication problem. Telomerase activity, leading to synthesis of telomeric DNA repeats, has been proposed to be an important step in the immortalization process of tumor cells. In the present study, 56 renal cell carcinomas were tested for telomerase activity using the sensitive TRAP (telomeric repeat amplification protocol). Forty of the analysed tumors (71%) were positive for telomerase activity, whereas none of the 56 corresponding normal kidney samples showed telomerase activity. All telomerase negative tumors had a reduction in mean telomere restriction fragment (TRF) length and a decrease in total telomere repeat hybridization signal, though cases were observed with an increase in peak TRF lengths. No obvious association between the presence of telomerase activity and clinicopathological parameters (histopathologic grade, DNA-ploidy, stage and clinical outcome) was found. The high frequency of detection of telomerase activity in the renal cell carcinomas indicates that this enzyme is likely to be an important factor involved in the evolution of this tumor type.

Base Sequence↗

Cell proliferation in renal cell carcinoma--a comparative study of cell kinetic methods.

Four different methods of assessing cell proliferation in renal cell carcinoma were compared in a total of 136 samples to analyze their degree of agreement and usefulness. The methods compared were flow cytometric S-phase (S-FCM) analysis, proliferating cell nuclear antigen expression detected by immunohistochemistry (PCNA-IHC), in vivo iododeoxyuridine incorporation analyzed with immunohistochemistry (IdUrd-IHC), and flow cytometry (IdUrd-FCM). The mean S-FCM fraction was 5.9%, compared with a mean PCNA-IHC labeling index of 4.7%. The mean labeling indices obtained by IdUrd-IHC and IdUrd-FCM were 1.2% and 1.7%, respectively. The four methods correlated well with each other. When the methods were compared according to Bland and Altman, good agreement was shown. A statistically significant difference in proliferation between diploid and aneuploid tumor samples was found with all methods (P < 0.001). The results showed that the four different methods provided comparable information on proliferative activity, although different cell cycle compartments were monitored.

Aneuploidy↗

Heterogeneity in renal cell carcinoma and its impact no prognosis--a flow cytometric study.

In the process of tumour progression genetic instability is the basis for the evolution of tumour cell clones with various genotypic and phenotypic characteristics causing heterogeneity. Renal cell carcinoma has a long prediagnostic growth period, which increases the probability of clonal evolution. We have studied 200 consecutive renal cell carcinomas, addressing the interrelationship between intratumour heterogeneity and clinicopathological factors. DNA ploidy patterns were analysed in multiple samples from each tumour using flow cytometry and compared with clinical stage, tumour invasion, metastatic rate and survival. Eighty-five of 192 evaluable tumours (44%) were homogeneous concerning DNA ploidy (62% diploid, 38% aneuploid). Among 107 heterogeneous tumours a majority (79%) contained aneuploid as well as diploid cell clones. Homogeneously diploid tumours had a lower incidence of local tumour spread compared with tumours with aneuploid cell clones (P < or = 0.001), but the frequency of distant metastasis at time of diagnosis was similar. The presence of aneuploidy in at least one sample from a tumour was a significant adverse prognostic factor (P < 0.001), whereas the degree of heterogeneity had no influence on survival. The frequent heterogeneity demonstrated indicates that multiple samples must be investigated to evaluate properly the malignant character of renal cell carcinoma.

Adult↗

Predictive value of DNA ploidy in bladder cancer treated with preoperative radiation therapy and cystectomy.

The predictive value of flow cytometric DNA analysis of cells from bladder washings was evaluated in 43 patients with muscle-invasive or recurrent superficial bladder cancer treated with preoperative radiotherapy and cystectomy. There was no correlation between ploidy status of the primary tumour and survival, neither was there any correlation between ploidy and the occurrence of residual tumour in the cystectomy specimens. Patients without residual tumours in the cystectomy specimen had significantly longer survival time than those with residual tumours. Concomitant carcinoma in situ was correlated with better survival, which is surprising, considering the malignant potential of this lesion. In this study DNA ploidy did not predict tumour response to radiotherapy nor was it of any prognostic significance.

Carcinoma in Situ↗

Proliferating cell nuclear antigen expression in renal cell carcinoma. Prognostic implications.

The proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with cells in active cell cycle. The expression of PCNA was evaluated immunohistochemically in 3-6 samples from 68 renal cell carcinomas. A total of 279 tumour samples were analysed using the monoclonal antibody PC-10, and the percentage of positively stained cell nuclei (PCNA-index) was determined. The tumour PCNA-index varied between 0.9-17.5%, with a mean value of 4.9%, significantly different from normal kidney cortex samples (p < 0.001). A significant difference in PCNA-index was found between the different tumour grades, whereas no significant difference was found between clinical stages. Concerning DNA ploidy, aneuploid tumours had a significantly higher PCNA-index compared with diploid tumours (p = 0.002). There was a significant survival advantage for patients with low tumour PCNA-indices (< 3.5%) compared with those with high indices (> 3.5%, p = 0.019), a difference also found for patients with non-metastatic disease (p = 0.012). Our data shows that PCNA expression can be analysed and that it may constitute an additional prognostic parameter for patients with renal cell carcinoma.

Adult↗

Serum beta 2-microglobulin and prognosis of patients with renal cell carcinoma.

Beta 2-Microglobulin (beta 2-M) was analysed in serum of 145 patients with renal cell carcinoma, and serum creatinine < 125 mumol/1 by a radioimmunometric method. Forty-nine (34%) patients had serum beta 2-M level > or = 3.0 mg/l. Of the patients with distal metastases 46% had elevated levels, compared with 19% with stage I disease. Serum beta 2-M correlated with histopathologic grade; 58% of the patients with poorly differentiated (grade 4) tumours had elevated levels compared with 18% in grade 1-2 tumours. Also tumour cell type was associated with serum beta 2-M; 52% of the patients with plasmic tumours had elevated levels compared with 6% in the clear cell type. In a univariate prognostic analysis elevated serum beta 2-M level was inversely correlated with survival time. Using a multivariate analysis the strong prognostic factors were clinical stage and tumour diameter. Weaker factors were age and cell type, whereas the prognostic value of serum beta 2-M disappeared. However, if tumour cell type was excluded from the analysis, serum beta 2-M was identified as a prognostic factor.

Adenocarcinoma↗

Maintaining low HIV seroprevalence in populations of injecting drug users.

OBJECTIVES: To describe prevention activities and risk behavior in cities where human immunodeficiency virus (HIV) was introduced into the local population of injecting drug users (IDUs), but where seroprevalence has nevertheless remained low (< 5%) during at least 5 years. DESIGN AND SETTING: A literature search identified five such cities: Glasgow, Scotland; Lund, Sweden; Sydney, New South Wales, Australia; Tacoma, Wash; and Toronto, Ontario. Case histories were prepared for each city, including data on prevention activities and current levels of risk behavior among IDUs. PARTICIPANTS: Injecting drug users recruited from both drug treatment and non-treatment settings in each city. INTERVENTIONS: A variety of HIV prevention activities for IDUs had been implemented in each of the five cities. RESULTS: There were three common prevention components present in all five cities: (1) implementation of prevention activities when HIV seroprevalence was still low, (2) provision of sterile injection equipment, and (3) community outreach to IDUs. Moderate levels of risk behavior continued with one third or more of the IDUs reporting recent unsafe injections. CONCLUSIONS: In low-seroprevalence areas, it appears possible to severely limit transmission of HIV among populations of IDUs, despite continuing risk behavior among a substantial proportion of the population. Pending further studies, the common prevention components (beginning early, community outreach, and access to sterile injection equipment) should be implemented wherever populations of IDUs are at risk for rapid spread of HIV.

HIV Infections↗