Biomedical subjects

P Lipponen

Publications and source records attributed to P Lipponen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Expression of p21(waf1/cip1) protein in transitional cell bladder tumours and its prognostic value.

OBJECTIVES: p21(waf1/cip1) protein is a cyclin-dependent kinase inhibitor able to arrest the cell at the G1 phase by inhibiting DNA replication through interaction with proliferating cell nuclear antigen (PCNA). Experimental analyses of human bladder cancer cell lines show that p21 might be considered a tumour suppressor gene since it is able to induce apoptosis like p53. The prognostic value and expression of p21(waf1/cip1) is incompletely studied in bladder cancer at present. METHODS: The expression of p21 protein was immunohistochemically analysed in paraffin-embedded specimens of 186 patients with primary transitional cell bladder tumours. The results of immunohistochemical analysis were related to known prognostic factors and complete long clinical follow-up data (over 11 years). RESULTS: The expression of p21(waf1/cip1) protein was significantly related to DNA ploidy, S phase fraction, mitotic index, apoptotic index, morphometric nuclear factors, and the expression of p53 and PCNA proteins, whereas it was unrelated to grade or TNM classification. In univariate survival analysis, the expression of p21(waf1/cip1) protein was not significantly related to prognosis. Independent prognostic factors were T category, papillary status and mitotic index. CONCLUSION: The results indicate that although the expression of p21(waf1/cip1) protein is related to indicators of cell proliferation, apoptosis and p53 expression, it has no better prognostic value than already established prognostic factors in bladder cancer.

Adult↗

PubMed1998

Usefulness of history-taking, physical examination and diagnostic scoring in acute renal colic.

OBJECTIVE: The accuracy of the clinical diagnosis of acute renal colic was studied in connection with the survey of acute abdominal pain by the Research Committee of the World Organization of Gastroenterology. The diagnostic efficiency of various clinical symptoms, signs and tests have not previously been analyzed in the diagnosis of acute renal colic, and therefore the study is of potential importance. METHODS: 1,333 patients presenting with acute abdominal pain were included in the study. The clinical findings in each patient were recorded in detail, using a predefined structured data collection sheet, and the collected data were compared with the final diagnoses of the patients. Twenty-three clinical history variables, 14 clinical signs and 3 tests were evaluated in a single variable and multivariate analysis. RESULTS: In multivariate logistic regression analysis, the most significant predictors of acute renal colic were urine, tenderness, renal tenderness, duration of pain and appetite. The sensitivity in detecting acute renal colic was 0.84, with a specificity of 0.99 and an efficiency of 0.98. To sum up the contributions of most significant diagnostic factors, a diagnostic score (DS) was built. This score incorporated independent variables, e.g. urine, tenderness, renal tenderness, duration of pain, appetite and sex. The DS reached a sensitivity of 0.89 in detecting acute renal colic, with a specificity of 0.99 and an efficiency of 0.99. CONCLUSIONS: The results clearly show that acute abdominal pain with normal appetite, short duration of pain (</=12 h), loin or renal tenderness and hematuria (erythrocytes >10) are indicative of acute renal colic, and therefore, in this particular clinical question, careful history-taking and physical examination are of utmost importance. In our study, the DS system performed well considering the simple nature of its structure. However, to minimize the risk to the patient, we recommend that the DS is used only as an aid in decision-making when there is uncertainty as to the diagnosis of acute renal colic and the need for immediate treatment. In addition, the possibility of obstructive pyelonephritis in combination with renal colic should be considered clinically.

Acute Disease↗

PubMed1998

A new versatile PC-based lung sound analyzer with automatic crackle analysis (HeLSA); repeatability of spectral parameters and sound amplitude in healthy subjects.

A versatile PC-based lung sound analyzer has been developed for short-term recording and analysis of respiratory sounds in research and clinical applications. The system consists of two sound sensors, a flow sensor, a filtering signal amplifier and a PC with a data acquisition card and software for measurement and analysis of the sounds. The analyses include phonopneumography, time expanded waveform analysis, spectral analysis with time averaged Fast Fourier Transform, frequency analysis in time domain (sonogram), and automatic detection and waveform analysis of crackles. Short-term repeatability of spectral parameters of tracheal and lung sounds was studied in 10 healthy subjects. The coefficients of variation (CoV) of the averaged quartile frequencies (F25, F50 and F75) of lung sounds during flow-controlled tidal breathing were 3.7, 4.0 and 8.9% in expiration and 2.7, 3.5 and 4.5% in inspiration, respectively. CoVs of the averaged F25, F50 and F75 of expiratory tracheal sounds were 6.9, 3.0 and 2.4%, and those of inspiratory tracheal sounds 6.3, 2.6 and 3.3%, respectively. Examples of lung sound analysis of samples containing adventitious sounds such as crackles and wheezes are presented. The results indicate that the median frequency has the best repeatability of quartile frequencies of breath sounds and they suggest that the variations of those parameters are low enough for diagnostic purposes. The results also suggest that the analyzer can be a useful new tool for pulmonary research in the fields of physiological and clinical short-term studies of respiratory sounds.

Adult↗

PubMed1998

Distribution of crackles on the flow-volume plane in different pulmonary diseases.

A new method to represent and evaluate crackles on the flow-volume plane is described. Characteristic crackle patterns were found in patients with pneumonia, bronchiectasis, chronic obstructive pulmonary disease, heart failure and cryptogenic fibrosing alveolitis. In addition to visual assessment, simple statistical parameters were used to describe the observed pathological phenomena.

Adult↗

PubMed1997

Expression of the apoptosis suppressing protein bcl-2 in prostatic adenocarcinoma is related to tumor malignancy.

BACKGROUND: The expression of bcl-2 protein has been related to histopathological features and prognosis in several epithelial tumors. In prostatic adenocarcinoma the prognostic significance of bcl-2 expression is mainly unexplored. METHODS: The expression of bcl-2 protein was assessed in 235 prostatic adenocarcinomas by using monoclonal bcl-2 protein antibody after microwave pretreatment of the cancer sections. The results of immunohistochemistry were related to histopathological features and prognosis of the patients. RESULTS: 71% of the tumors were bcl-2 negative, in 18% of cases the expression was weak, and in 11% of cases strong. The fraction of bcl-2 positive cells was variable (mean [SE]: 15 [2]%). The expression of bcl-2 protein was positively correlated to high T-category, metastatic disease, and poor histological differentiation of the tumor. Tumors that were aneuploid and rapidly proliferating frequently expressed bcl-2 protein, while tumors we densely infiltrated by inflammatory cells rarely expressed bcl-2. The expression of bcl-2 protein was related to lowered survival probability in univariate analysis, while in multivariate analysis the expression of bcl-2 had no independent prognostic value. CONCLUSIONS: The expression of bcl-2 protein in prostatic adenocarcinoma is related to tumor malignancy, but the prognostic significance of the expression requires further analyses, particularly in localized tumors.

Adenocarcinoma↗

PubMed1997

Nuclear morphometry as a predictor of disease outcome in gastric cancer.

Nuclear morphometric features including nuclear area (NA), nuclear perimeter (PE), their variation (SDNA, SDPE), and mean largest and smallest nuclear diameters (Dmax, Dmin) were examined in 116 patients with stage I-II gastric adenocarcinoma. Morphometric measurements were compared with tumour differentiation, depth of invasion (pT), lymph node status (pN), and Lauren classification. All morphonuclear features were significantly larger in the intestinal type than in the diffuse type of cancer. None of the morphometric variables was related to TNM status or tumour size. Nuclear area and perimeter and their variation were closely related to survival in univariate analysis, patients with small and regular nuclei surviving longer. In the multivariate analysis, pT, pN, perineural invasion, and the standard deviation of nuclear perimeter (SDPE) were independent predictors of survival. Nuclear morphometry is a quantitative, objective, and highly reproducible method of revealing malignant features in several neoplasms. The results of the present study suggest that nuclear morphometric data may help in defining prognosis in gastric cancer.

Adenocarcinoma↗

PubMed1997

Prognostic value of epidermal growth factor expression in breast cancer.

A series of 198 female breast cancer biopsies were analysed immunohistochemically for the expression of epidermal growth factor (EGF), with special emphasis on its prognostic significance. A total of 67/198 tumours (33.8%) were EGF-positive, 24 (12%) of which showed strong expression of EGF. EGF was usually expressed in the cytoplasm of the cancer cells but, in 22 cases, the normal ducts adjacent to the cancer showed positive staining as well. Strong EGF expression was related to distant metastases at diagnosis (P = 0.04). Oestrogen(ER)- and progesterone-receptor(PR)-negative tumours showed EGF positivity with equal frequency (P = 0.05 in both). Axillary lymph node status, histological type, tumour size, histological grade, S-phase fraction, mitotic index or cancer recurrence did not show any statistical correlation with EGF expression. Tumour size (P = 0.007), axillary lymph node involvement (P = 0.003) and ER content (P = 0.03) were independent prognostic factors in multivariate survival analysis, whereas EGF positivity, as an independent factor, had no effect on survival. In univariate analysis, however, EGF positivity predicted a more favourable outcome in axillary-lymph-node-positive tumours (P = 0.04). The results suggest that immunohistochemical assessment of EGF expression has hardly any clinical significance in addition to the well-established prognostic factors in breast cancer.

Breast Neoplasms↗

PubMed1997

Mitotic index in the subrenal capsule assay as an indicator of the chemosensitivity of ovarian cancer.

The subrenal capsule assay (SRCA) is used in clinical oncology to assess the sensitivity of individual malignant tumors to various anticancer agents and their combinations. Mitotic indices reflect cancer cell proliferation and have prognostic value in epithelial neoplasms, including ovarian carcinoma. We combined the two tests (SRCA, mitotic index) by evaluating the numbers of mitotic figures per square millimeter of neoplastic epithelium (M/V) in paraffin-embedded tumor samples after SRCA. The M/V index was compared with the tumor size measurement (dTS), which is used in conventional SRCA to predict the drug response. Histology examination showed insignificant changes in the size of tumor transplants due to host reaction but disclosed a number of potential errors in the use of dTS to evaluate transplant growth and drug effects. In our series of 62 patients with advanced ovarian carcinoma the M/V value was superior to the dTS in explaining the clinical response after 6 months as assessed at second-look laparotomy. Patients showing no response had significantly higher M/V values than did those displaying complete or partial responses (P < 0.033). The use of 6 mitotic figures/mm2 as a limit differentiating responders from nonresponders resulted in an overall predictive accuracy of 79% in the logistic regression analysis. In comparison to the FIGO stage, residual tumor size, and the dTS, the M/V value obtained for the cytostatic combination given to the patient was the single most significant factor predicting the 6-month clinical response. The results indicate that the combined use of the M/V index and SRCA is a promising new approach to prediction of the drug response in ovarian adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Prognostic value of Ki-67 expression in renal cell carcinomas.

OBJECTIVE: The aim of the study was to determine the prognostic power of Ki-67 immunostaining in renal cell carcinomas (RCC). METHODS: Clinical follow-up data were reviewed in 111 RCC and the results of Ki-67 immunolabelling were correlated to standard prognostic factors and survival data of the patients. RESULTS: Ki-67 expression correlated with tumor grade (p < 0.0001) and mitotic activity (p < 0.0001). In survival analysis Ki-67 expression could be used to divide patients into different prognostic groups (p = 0.0003). In separate analysis with M0 tumors Ki-67 immunolabelling was a powerful predictor of survival (p = 0.0016) as well as disease-free survival (DFS; p = 0.0067). In T1-2N0M0 tumors Ki-67 immunolabelling was superior (p = 0.0005) to other prognostic factors in survival analysis as well as in predicting DFS (p = 0.0006). Grade-2 tumors could be separated into distinct prognostic groups according to Ki-67 labelling (p = 0.0098). In Cox's multivariate analysis Ki-67 was an independent prognostic factor in all three subgroups of RCC. CONCLUSIONS: The results show that Ki-67 expression is an independent prognostic factor in renal adenocarcinoma and could be applied in defining proper therapy for patients suffering from this malignancy.

Adult↗

PubMed1997

Value of Ki-67 immunolabelling as a prognostic factor in prostate cancer.

OBJECTIVE(S): The aim of the study was to analyze the results of Ki-67 immunostaining in prostatic adenocarcinoma and to assess its prognostic value. METHODS: Clinical follow-up data was reviewed in 190 prostatic adenocarcinomas and the results of Ki-67 immunolabelling were correlated to standard prognostic factors and survival data of the patients. All stage and grade categories were included. RESULTS: Ki-67 expression correlated significantly with histological differentiation of tumors, indicators of cell proliferation, perineural growth, density of tumor-infiltrating lymphocytes and TM classification. In survival analysis, Ki-67 expression was able to discriminate patients into different prognostic groups (p = 0.0035). In a separate analysis including T1-2M0 tumors, Ki-67 immunolabelling was a significant predictor of survival (p = 0.0258). In Cox's multivariate analysis Ki-67 was an independent prognostic factor in the entire cohort. CONCLUSIONS: The results show that Ki-67 expression is a potentially useful prognostic factor in prostatic adenocarcinoma and it could be used as an additional criterion in defining a correct prognostic category in this malignancy.

Adenocarcinoma↗

PubMed1996

The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer.

A series of 191 female breast carcinomas (with long-term follow-up) were analysed immunohistochemically (with a monoclonal MIB1 antibody) for Ki-67 (a proliferation marker) expression with special reference to well-established prognostic factors and patient survival. Expression of Ki-67 was directly related to the S-phase fraction (P < 0.0001), the volume-corrected mitotic index (P < 0.0001), histological grade (P < 0.0001), the apoptotic index (P < 0.0001), oestrogen and progesterose receptor content (P < 0.0001 for both) and p53 accumulation (P = 0.001). No correlation was found between Ki-67 expression and lymph node status (P = 0.25), metastasis at operation (n = 0.81) or tumour size (n = 0.38). The proliferation rate, as measured by image analysis of Ki-67 expression, predicted survival in the entire cohort (P = 0.001) and in axillary-lymph-node-negative (ANN) patients (P = 0.003). The difference in recurrence-free survival between the high- and low-expression groups was greatest in ANN tumours, 40% (P = 0.008). In axillary-lymph-node-positive tumours, the Ki-67 expression was not significantly related to recurrence-free survival (P = 0.723). The results of multivariate survival analysis showed that tumour size, axillary lymph node status, and mitotic index were independent prognostic factors in the entire series whereas, in ANN cases, tumour size and Ki-67 labelling were independent prognostic factors. These findings imply that Ki-67 expression could be an important prognostic determinant in breast cancer. Because of the evident loss of the predictive power of tumour size in the 1990s, the prognostic value of Ki-67 expression may even be accentuated in the currently diagnosed small breast carcinomas.

Breast Neoplasms↗

PubMed1996

Recurrence of urinary tract infection in a primary care setting: analysis of a 1-year follow-up of 179 women.

In a prospective study, 179 adult women (age range, 17-82 years) were followed up for 12 months after an index episode of community-acquired cystitis caused by Escherichia coli. Episodes of symptomatic urinary tract infection (UTI) were recorded, and urinary isolates were compared with the index episode isolate; 147 UTI episodes were detected during the follow-up. Of these episodes, 131 were classified as recurrences occurring at least 1 month after the index episode; 44% of the patients had recurrences. A history of UTI increased the risk of recurrence; only 11.8% of the 17 patients without previous episodes of UTI had at least one recurrence, while 47.5% of those with previous episodes had at least one recurrence (OR, 6.8; univariate logistic regression). E. coli caused 78% of the recurrent episodes. Phenotypic and genotypic analysis of E. coli strains showed that one-third of the recurrences were caused by the index episode strain, which could persist and cause recurrences throughout the 1-year follow-up period. The prevalence of adhesins or other identified virulence factors for UTI among the recurrence strains was identical to that among the index episode strains. The presence of these factors did not affect the risk of recurrence but did increase the likelihood that the index episode strain would persist and cause recurrent episodes of UTI.

Adolescent↗

PubMed1995

Apoptosis suppressing protein bcl-2 is expressed in well-differentiated breast carcinomas with favourable prognosis.

The expression of bcl-2 protein was analysed immunohistochemically in 202 female breast carcinomas. The intensity of bcl-2 expression was inversely related to tumour grade (P < 0.0001), tumor necrosis (P < 0.0001), mitotic index (P < 0.0001), oestrogen receptor content (P < 0.0001), progesterone receptor content (P = 0.0007), S-phase fraction (P = 0.00047), and apoptotic index (P = 0.087). A high fraction of bcl-2-positive cells was related to ductal or lobular type (P = 0.03) and slight nuclear pleomorphism (P = 0.03). Heterogeneous expression of bcl-2 protein was associated with high grade (P = 0.02), severe nuclear pleomorphism (P = 0.02), DNA aneuploidy (P = 0.018), high S-phase fraction (P = 0.05), and early metastasis (P = 0.03). Intense expression of bcl-2 protein was significantly related to favourable outcome in the entire cohort (P = 0.0013), as well as in axillary lymph node-negative (ANN) tumours (P = 0.0124). Long recurrence-free periods in the entire cohort (P = 0.037) and in ANN tumours (P = 0.08) were confined to cases with intense expression of bcl-2 protein. In multivariate analysis, bcl-2 expression had no independent prognostic value in the entire cohort or in axillary lymph node-negative breast carcinomas, whereas it was a weak independent prognostic factor in axillary lymph node-positive breast carcinomas.

Adult↗

PubMed1995

Expression of p53 protein has no independent prognostic value in breast cancer.

A series of 392 female breast carcinomas was analysed immunohistochemically for expression of p53 protein with special emphasis on the role of p53 as an independent prognostic factor. Altogether, 54.8 per cent of the carcinomas expressed p53 protein, with the mean [standard error (SE)] fraction of positive nuclei being 17.1 per cent (1.2 per cent). Expression of p53 protein was independent of tumour metastasis at diagnosis, axillary lymph node status, tumour diameter, histological type, tubule formation, proportion of intraductal growth, margin formation, necrosis, DNA ploidy, and S-phase fraction. A high fraction of p53-positive nuclei was significantly related to patient age under 70 years, high grade, severe nuclear pleomorphism, dense infiltration of tumour by lymphocytes, high mitotic index, and high apoptotic index (for all, P < 0.05). Impaired survival probability in the entire cohort (P = 0.05) and in the axillary lymph node-positive (ANP) tumours (P = 0.015) was associated with a fraction of p53-positive nuclei less than 25 per cent, while in the axillary lymph node-negative (ANN) tumours, expression of p53 had no prognostic value. In multivariate analysis, independent prognostic predictors included axillary lymph node status, tumour diameter, and mitotic index. In the ANN tumours, tumour diameter, fraction of p53-positive nuclei, and tumour grade were independent prognostic factors, whereas in the ANP tumours, diameter and mitotic index were the two independent prognostic factors. The results suggest that abnormal expression of p53 protein is only a weak independent prognostic factor in female breast cancer.

Adult↗

PubMed1995

Mitotic activity and prognosis in prostatic adenocarcinoma.

Mitotic figures were quantitated by two different methods (number of mitotic figures in 10 high power fields, MI; number of mitotic figures/mm2 of neoplastic epithelium, M/V) in a series of 303 prostatic adenocarcinomas, and the results were related to clinical and histological features as well as to prognosis. Gleason score and mitotic indices were significantly interrelated. Invasive T3-4 tumors showed higher mitosis counts than did the local ones, and metastasis at the time of diagnosis was related to mitotic indices as well. Progression and progression-free survival were related significantly to Gleason score and mitotic indices. In univariate survival analysis, T-category, M-category, Gleason score, MI, and M/V were significant prognostic factors. In multivariate analysis, independent predictors of survival were M-category, T-category, Gleason score, patient age, and the M/V index. If the Gleason score was not included, M/V included all the available prognostic information in T1-2M0 carcinomas. The results show that, in addition to the conventional Gleason grading system, mitotic indices are useful prognostic parameters while evaluating the long-term prognosis in prostatic adenocarcinoma.

Adenocarcinoma↗

PubMed1995

Nuclear morphometry is of independent prognostic value only in T1 prostatic adenocarcinomas.

A series of 325 patients with prostatic adenocarcinoma followed-up for over 13 years was subjected to histomorphometric analysis for the following prognostic factors: the Gleason score and 10 nuclear morphometric factors (mean nuclear area, nuclear perimeter, shortest and longest nuclear axis, form factor and their SDs), using the IBAS 1&2 image analyzer. Nuclear factors, Gleason score (P = 0.0013-0.0148), and T-category (P = 0.004-0.0107) were significantly interrelated, while the M-category was independent of the morphometric parameters. Nuclear factors (P = 0.0003-0.5), Gleason score (P < 0.0001), T-category (P < 0.0001) and M-category (P < 0.0001) predicted the disease outcome. In T1-2M0 tumors, the T-category (P = 0.0001), Gleason score (P < 0.0001), SD of nuclear area (P = 0.057), SD of nuclear perimetry (P = 0.039), mean shortest nuclear axis (P = 0.030), SD of the shortest nuclear axis (P = 0.0045), SD of the longest nuclear axis (P = 0.009), and nuclear form factor (P = 0.0123) were significant prognostic factors. In the multivariate survival analysis, the nuclear area had independent prognostic significance only in T1 tumors, whereas in other subcategories, the clinical stage, Gleason score, and patient age included all the available prognostic information. The results indicate that nuclear morphometric measurements are of borderline significance only in evaluating the intrinsic malignancy of prostatic adenocarcinoma.

Adenocarcinoma↗

PubMed1995

Expression of retinoblastoma gene (Rb) protein in T12M0 prostatic adenocarcinoma.

The expression of Rb protein was analysed by immunocytochemical methods in 118 patients with T12M0 prostatic adenocarcinoma who were followed-up for more than 12 years. Rb protein was expressed in 117/118 (99%) tumours. The fraction of positive nuclei was (mean +/- SD, 92 +/- 19%) and only one tumour was completely negative for Rb protein. Abnormal expression of the Rb protein (in fewer than 90% of cells) was independent of the T category while there was a significant relationship between DNA ploidy (P = 0.0138), S-phase fraction (P = 0.0042) and expression of the Rb protein. Abnormal expression of the Rb protein had no prognostic value while T category (P = 0.0017), Gleason score (P = 0.0097), DNA ploidy (P = 0.0034), S-phase fraction (P = 0.0179) and mitotic index (P = 0.0001) were significant prognostic factors. In multivariate analysis the only independent predictor was the mitotic index [Risk ratio (RR) (95%CI) = 7.4(2.4-22.5), P = 0.004]. The results show that Rb protein immunohistochemistry has hardly any prognostic significance in prostatic adenocarcinoma whereas direct measurement of cell proliferative activity contains significant prognostic information.

Adenocarcinoma↗

PubMed1995

Expression of retinoblastoma gene protein (Rb) in breast cancer as related to established prognostic factors and survival.

The expression of retinoblastoma gene product (Rb protein) was studied by immunohistochemical analysis of 205 cases of breast cancer. Rb protein was invariably expressed in non-neoblastic breast epithelium, in dysplastic and hyperblastic lesions adjacent to tumours, and none of the breast tumours was totally negative for Rb protein. According to the scoring system used, the expression of Rb protein was abnormal in 36.6% of cases. Abnormal expression of Rb protein was significantly related to grade (P < 0.00004), type (P = 0.0183), margin formation (P = 0.0116), DNA ploidy (P < 0.0002) and nuclear pleomorphism (P < 0.0001). Abnormal expression of Rb protein was related to high S phase fraction (P = 0.004), high mitotic index (P < 0.001) and high morphometric nuclear factor values (P < 0.01). The expression of Rb protein had no prognostic value in univariate or multivariate analysis. The results show that the tumour suppressor gene Rb participates in the growth regulation of breast cancer cells in vivo, but immunohistochemical assessment of the expression of Rb protein has no prognostic significance in clinical breast cancer over already established prognostic factors.

Adult↗