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Biomedical subjects

R Bloigu

Publications and source records attributed to R Bloigu.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between histopathological features and the course of idiopathic pulmonary fibrosis/usual interstitial pneumonia.

BACKGROUND: Fibroblastic focus (FF) is the typical histopathological feature of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). A study was undertaken to analyse FF at diagnosis, to analyse the histopathological findings at necropsy, and to examine their association with the course of the disease. METHODS: A retrospective study was made of 76 UIP cases collected over a period of 30 years from one university hospital; 64 had idiopathic IPF. The surface area of one slide of each lung biopsy specimen was defined by image analysis and the total number of FF was quantified. The histological features of necroscopic lung samples were re-analysed in 11 cases. Clinical follow up information was obtained from the registers. RESULTS: Patients with < or =50 FF/cm(2) (n = 34) in the lung biopsy specimen had a median survival of 89 months (95% CI 38 to 140) compared with 49 months (95% CI 36 to 62) in those with >50 FF/cm(2) (n = 42, p = 0.0358). Diffuse alveolar damage (DAD) was detected in 10 necropsy samples and almost prevented the histopathological confirmation of UIP in six cases. Accumulation of neutrophils occurred in nine cases. There was no association between FF at diagnosis and DAD at necropsy, or between FF and exacerbation of the disease before death. CONCLUSIONS: The number of FF in lung samples before death is associated with poor survival but not with DAD, which is a common feature in necropsy specimens of patients with UIP. FF cannot predict an acute exacerbation of IPF.

Adult↗
PubMed2004

Decreased bone mineral density and content in neurofibromatosis type 1: lowest local values are located in the load-carrying parts of the body.

Neurofibromatosis type 1 (NF1) is a dominantly inherited disease. Skeletal ailments such as short stature, kyphoscoliosis, tibial bowing and pseudarthrosis are common osseous manifestations of NF1. Previously, a correlation with scoliosis and decreased bone mineral density (BMD) of the lumbar spine has been reported in 12 NF1 patients. A total of 35 NF1 patients and 26 healthy controls were included in the present study. Of the participants over 20 years of age (26 NF1 patients and all controls) 14 were male and 12 were female, seven of whom were premenopausal. The controls were matched for age, sex and body mass index (BMI). Physical activity and medical history of NF1 patients were evaluated to screen the fractures and osseous manifestations of the disease and to rule out the factors that effect BMD. BMD and bone mineral content (BMC) were measured with DXA, using a total body program. The present study detected a lowered bone mineral density (p =0.028) and content (p <0.001) in NF1 patients of both sexes. The results of the present study also show that NF1 patients have an increased risk for osteoporosis. Among NF1 patients seven cases of osteoporosis and 13 cases of osteopenia were detected. In controls, one case of osteoporosis and 13 cases of osteopenia were detected. The location of the lowest local BMD was clustered to the load-carrying parts of the body in NF1 patients. Physical activity and the medical history of the NF1 patients did not explain the decreased BMD and BMC. The findings of the present and previous studies suggest that the pathogenesis of the osseous manifestations in NF1 may involve impaired development of the skeletal system and impaired maintenance of bone structure.

Absorptiometry, Photon↗
PubMed2003

A mutant TP53 gene status is associated with a poor prognosis and anthracycline-resistance in breast cancer patients.

This study evaluates the prognostic and predictive relevance of a mutated p53 in a series of 254 samples from primary breast cancer patients. C-erbB-2 analysis was defined in a limited subpopulation of 79 patients. p53 and c-erbB-2 status was analysed by immunohistochemical staining of the tumour samples. Positive p53 immunostaining was present in 86 cases (34%) and correlated with a high malignant grade, negative progesterone receptor status and ductal histology of tumour. C-erbB-2 positivity was seen in 38 samples (48%). Within an average follow-up time of 74 months, 121 patients developed recurrent or metastatic disease. Patients with mutated p53 showed a statistically significant shorter overall survival and disease-free survival in both univariate and multivariate analyses. The worst clinical outcome was seen in patients who were both p53- and c-erbB-2-positive. The response rate to anthracycline-based chemotherapy in metastatic disease was low in the p53-positive cases. Our results help to clarify the independent prognostic role of a mutated p53 status in breast cancer patients, indicating that this gene might be predictive of anthracycline resistance. Patients with a mutant p53 status and overexpressing c-erbB-2 should be regarded as high-risk cases.

Adult↗
PubMed2002

Prospective population-based study on the survival of patients with lung cancer.

The purpose of this study was to evaluate the change, over 20 yrs, in the survival of lung cancer patients in a population-based study. Information on all patients with lung cancer in a defined geographical area during 1990-1992 (n=602) was prospectively gathered. The survival of these patients was assessed and also compared with the results of a similar study in the same area during the years 1968-1971 (n=446). The 5-yr survival had improved during 20 yrs from 4% to 12%. The 5-yr survival of the patients with squamous cell carcinoma had increased from 6% to 16%, and adenocarcinoma from 4% to 19%, whereas the survival of small cell carcinoma had remained the same (2% and 3%, respectively). Even though the recent patients were older than those of the earlier series the proportion of surgically treated patients had remained the same (16% and 20%), but the 5-yr survival of patients who had been operated on had increased significantly from 23% to 48%. The differences in survival in the second cohort (1990-1992) between histological types (Chi-squared logrank=59.2), tumour, node, metastasis stages (Chi-squared logrank=199.6), symptomatic stages (Chi-squared logrank=120, p<0.001) and treatment (Chi-squared logrank=277) were significant. Based on this study the independent prognostic factors for better survival of lung cancer patients are tumour, node, metastasis stages I and II, surgical treatment and Feinstein's symptomatic stages I and II.

Adenocarcinoma↗
PubMed2001

c-erbB-2 positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease.

The aim of this work was to evaluate the prognostic and predictive values of c-erbB-2 in breast cancer. 650 patients were enrolled. The amplification/overexpression of c-erbB-2 from fresh frozen or paraffin-embedded breast tumour tissue samples was analysed by polymerase chain reaction (PCR) technique (75%), immunohistochemically (17%) or by Southern blot analysis (8%). 126 patients (19%) were positive for c-erbB-2. 148 patients developed metastatic disease, but only 35 were positive for c-erbB-2. Positivity for c-erbB-2 was significantly associated with node positivity, large tumour size, high grade of malignancy, low receptor status, postmenopausal status, and with a shorter overall survival. In multivariate regression analysis, only tumour size and nodal involvement were risk factors for poor survival when analysed separately together with c-erbB-2 and receptor status. Metastatic patients with c-erbB-2 positivity had a significantly shorter survival and disease-free survival (DFS) than the c-erbB-2-negative patients. 29 advanced patients with c-erbB-2 positivity showed a poor response rate to hormonal, non-anthracycline-based and anthracycline-based therapies. Positivity for the c-erbB-2 is a poor prognostic factor in breast cancer, but it also emerges as predictive of the response to hormonal or chemotherapy treatment once the disease has recurred.

Antineoplastic Agents, Hormonal↗
PubMed2000

Loss of heterozygosity at chromosomes 3, 6, 8, 11, 16, and 17 in ovarian cancer: correlation to clinicopathological variables.

Tumor specimens from 78 epithelial ovarian cancer patients were examined for loss of heterozygosity (LOH) at 11 microsatellite markers at chromosomes 3p14.2, 6q27, 8p12, 11p15.5, 11q23.1-q24, 16q24.3, and 17p13.1, to evaluate the involvement, possible clustering, and prognostic significance of these lesions in the progression of the disease. The LOH analysis was performed on polymerase chain reaction (PCR)-amplified DNA from sections of paraffin-embedded tumor and normal tissue pairs. In addition to primary tumors, specimens of metastatic tissues were studied from 19 patients. In the combined results from primary and metastatic tumors, LOH frequencies varied between 31% (6q27) and 69% (17p13.1). Only LOH at chromosomal regions 3p14.2 (D3S1300), 11p15.5 (D11S1318), 11q23.3-q24 (D11S1340 and D11S912), 16q24.3 (D16S476 and D16S3028), and 17p13.1 (D17S938) was associated with an adverse disease course. Our results indicate that LOH at 17p13.1 occurs independently from the other chromosomal sites studied, and is an early event in ovarian tumorigenesis. The LOH at 16q24.3, 11q23.3/q24, and 11p15.5 seems to occur later. The LOH at 11p15.5 and 11q23.3 was associated with reduced cancer-specific survival time; therefore, the studied markers could be located close to genes with influence on patient survival. Of the studied chromosomal regions, the most important tumor suppressor genes involved in the evolution of ovarian cancer appear to be located on chromosomes 11, 16, and 17. The genetic heterogeneity observed in primary and metastatic specimens demonstrates that there are multiple pathways involved in the progression of ovarian cancer.

Chromosome Deletion↗
PubMed1999

Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome.

A total of 811 intrauterine insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis.

Clomiphene↗
PubMed1999

An epidemiological study of lung cancer: history and histological types in a general population in northern Finland.

A prospective epidemiological study was conducted to assess the incidence, diagnosis, histology and surgical treatment of lung cancer in northern Finland. The results were compared with those obtained in a similar survey 20 yrs earlier. Most of the patients with a suspected lung tumour were interviewed (72%) and the information was combined with that obtained from the national cancer registry. All pathological specimens were re-evaluated by a pathologist. A total of 602 new lung cancer cases (85% male, 15% female) were diagnosed during the years 1990-1992, the annual incidence per 100,000 being 63 for males and 9.5 for females. The number not reported to the Finnish Cancer Registry was low (<1%). Lung cancer was confirmed histologically in 381 cases (63%) and in addition cytologically in 135 cases (23%). Squamous cell carcinoma was the most common histological type (40%), the proportion of adenocarcinoma being 26%, small cell carcinoma 24% and large cell carcinoma 4%. The incidence of lung cancer had decreased significantly among males (from 87 to 63 per 100,000) compared with 20 yrs earlier but had increased among females (from 4.1 to 9.5), chiefly on account of adenocarcinoma. The findings of this prospective study show an increase in the incidence of lung adenocarcinoma among females, a histological type which is less closely related to smoking than the other cancers. This suggests that other risk factors may play an increasing role in the aetiology of lung cancer.

Aged↗
PubMed1998

Chromosome 11q22.3-q25 LOH in ovarian cancer: association with a more aggressive disease course and involved subregions.

Chromosome 11q deletions are common in various malignancies, including ovarian cancer. However, the clinical significance of these genetic lesions as well as their more precise chromosomal location is largely unknown. Here we have examined epithelial ovarian cancer material from 49 patients for loss of heterozygosity (LOH) using nine microsatellite markers on 11q22.3-q25 and evaluated the effect of observed deletions with regard to different clinicopathological variables. LOH was detected in 61% of the patients. Interestingly, LOH for the D11S1340 marker locus at 11q23. 3 seemed to be associated with significantly reduced survival times (P = 0.005) and serous tumor histology (P = 0.036). LOH for D11S912 at the more distal 11q24-q25 location correlated with a higher tumor stage (P = 0.003), serous tumor histology (P = 0.015), and finding of residual tumor (P = 0.047), but not directly with survival times (P = 0.320). The majority of the analyzed tumors simultaneously displayed deletions at two distinct 11q regions, A and B, which are proximal and distal to D11S1347/NCAM (11q23.2-q23.3), respectively. Only LOH for two markers (D11S1340 and D11S912) of the B region seemed to be directly associated with a more aggressive disease course. Therefore, it appears that deletions of the ataxia telangectasia gene of the A region would not be crucial for determining the outcome of ovarian cancer. Our present results indicate that a survival factor gene in ovarian cancer would be located close to D11S1340 at 11q23.3. This corresponds well to our earlier observation in breast cancer, suggesting the involvement of a shared survival factor gene in both diseases.

Chromosomes, Human, Pair 11↗
PubMed1997

Apoptosis in operated small cell lung carcinoma is inversely related to tumour necrosis and p53 immunoreactivity.

The present study was undertaken to analyse the extent of apoptosis in operated small cell lung carcinoma (SCLC) by using in situ labelling of the oligonucleosomal DNA fragments by terminal transferase. The extent of apoptosis was compared with the cell proliferation activity, as determined by Ki-67 immunohistochemistry; with the volume density of necrosis (per cent), as determined by the morphometric point counting method; and with the occurrence of immunohistochemically detectable p53 and bcl-2 proteins. By in situ labelling, remarkably high apoptotic indices (from 0.08 to 8.10 per cent) were seen in SCLC. A high percentage of SCLSs also showed an exceptionally high proliferation activity. Aberrant accumulation of p53 protein was seen in 37.5 per cent and bel-2 overexpression in 50 per cent of SCLCs. Necrosis was seen in 82.5 per cent of SCLCs. The extent of apoptosis was inversely related to the extent of tumour necrosis (P = 0.05) and to p53 protein accumulation (P = 0.008). A positive association was found between the extent of apoptosis and bel-2 immunoreactivity (P = 0.02). The apoptotic indices (per cent) correlated with the age (P < 0.05) and total smoking time of the patients (P = 0.06).

Apoptosis↗
PubMed1997

Is routine ipsilateral adrenalectomy during radical nephrectomy harmful for the patient?

To investigate the effects of unilateral adrenalectomy on the postoperative course and laboratory parameters, 40 patients with a renal tumour were randomized either to undergo (n = 20) or not to undergo (n = 20) ipsilateral adrenalectomy. Adrenal hormone (cortisol, epinephrine, norepinephrine and aldosterone), adrenocorticotropic hormone, electrolyte, creatinine, growth hormone, glucose, insulin and free fatty acid concentrations were measured preoperatively and postoperatively. Cortisol and epinephrine concentrations were elevated immediately after the operation but returned to preoperative levels within the first 2 postoperative days. There were no significant differences between the adrenalectomy and non-adrenalectomy groups, except that the cortisol concentration was higher in the latter in the afternoon of the day of surgery. The conclusion is that no long-term shortage of adrenal hormones is caused by unilateral adrenalectomy. Other metabolic and endocrine responses were identical in the groups. Thus ipsilateral adrenalectomy does not seem to be harmful to the patient and the need for it must be resolved on the basis of local tumour factors.

Adrenalectomy↗
PubMed1996

Ten-year survival after resection for lung carcinoma. Effect of blood transfusion and tumour stage on outcome.

The objectives were to evaluate the prognosis in resected lung cancer and to observe if perioperative blood transfusion adversely affects the prognosis. Of 208 patients with resection for lung cancer in 1978-1980, all but five were smokers: 127 had squamous cell and 81 non-squamous cell carcinoma. Stage I disease was found in 143 patients. (69%), stage II in 18 (9%) and stage IIIa in 47 (23%). Five-year survival was 52% in stage I, 29% in stage II and 7% in stage IIIa tumour; the respective 10-year rates were 37, 19 and 3%. Patients given perioperative blood transfusion (n = 95) had poorer prognosis than the non-transfused patients. According to Cox multivariate analysis, however, the relative risk of death was only slightly increased by perioperative transfusion (p = 0.07). In patients with stage II or IIIa carcinoma at diagnosis, this relative risk was 2.17 and 4.99 times higher than in stage I (p = 0.004 and p = 0.0001). Long-term survival thus was related to extent of the disease at diagnosis rather than to numbers of blood transfusions.

Adult↗
PubMed1995

p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis.

Accumulation of the tumour suppressor gene p53 product due to a gene mutation is frequently seen in human carcinomas, including lung carcinoma. Another indirect mechanism involving p53 in malignant growth relates to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild-type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo-alveolar carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM-1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty-six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow-up of 12-176 months, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 protein accumulation and the presence of HPV DNA was found.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1995

Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma.

This study was undertaken to determine the extent of apoptosis in lung carcinoma and to evaluate it as a prognostic marker. A series of 75 lung carcinomas (47 squamous cell carcinomas, 24 adenocarcinomas, 3 small cell carcinomas, and 1 large cell carcinoma) was analyzed for the extent of apoptosis by using the 3' end-labeling method of DNA in tissue sections. Apoptosis was correlated with the rate of cell proliferation, the immunohistochemically detectable p53 and bcl-2, the extent of tumor necrosis, and the survival data. The end-labeling method allowed a precise evaluation of the extent of apoptosis. In tumor tissue, the number of apoptotic bodies was roughly 2-fold greater than the number of apoptotic cells, whereas in nonneoplastic control tissues, the ratio was 1:1. The apoptotic indexes (percentages of apoptotic cells and bodies among tumor cells) were slightly higher in adenocarcinoma than in squamous cell carcinoma. There was no association between the extent of apoptosis and the expression of proliferating cell nuclear antigen or p53. On the other hand, tumor necrosis correlated significantly with proliferating cell nuclear antigen and p53 positivity (P = 0.00025 and 0.00087, respectively). Surprisingly, the extent of apoptosis was also found to be independent of the expression of bcl-2. Patients with apoptotic indexes greater than 1.5% had significantly shorter survival time than patients with apoptotic indexes equal to 1.50% or less (P < 0.01 by log rank). Aberrant p53 positivity also predicted a poor prognosis (P < 0.002 by log rank). By multivariate analysis, enhanced apoptosis showed a 1.9-fold risk (P = 0.04), and p53 positivity showed a 2.3-fold risk (P = 0.005) for a shortened survival. We conclude that both enhanced apoptosis and p53 positivity are independent prognostic markers in non-small cell lung carcinoma, predicting shortened survival time of the patients.

Aged↗
PubMed1995

Survival of patients after resection for lung cancer. Predictive value of staging by CT vs thoracotomy.

PURPOSE: The predictive value of staging of primary lung cancer by CT and thoracotomy with respect to survival was assessed in a series of 151 consecutive patients. MATERIAL AND METHODS: The new international staging system for lung cancer was used, with an additional indeterminate stage employed for cases in which a definite classification was impossible by CT. RESULTS: The survival rate curves for the stage groups assessed at CT and thoracotomy showed moderate to good parallelism. The patients with tumor stage I at thoracotomy but indeterminate or IIIa at CT had a significantly lower survival rate than those scored stage I at both. It was concluded that a sign of tumor spread obtained at any of the investigations should lead to an active approach, increasing the radicality of surgery or omitting noncurative operations.

Adult↗
PubMed1994

p53 immunohistochemical positivity as a prognostic marker in intracranial tumours.

The frequency and scale of positive p53 immunohistochemistry in 107 intracranial tumours of different types was studied as a possible prognostic marker using a polyclonal antibody CM-1 which detects both the wild-type and mutated p53 proteins. Fifty of the tumours (46.7%) showed nuclear p53 positivity with different percentages of positive nuclei. The positivity was concentrated in glial tumours of which 52.8% were positive. Forty-two of seventy-four astrocytomas (56.8%), 4 of 12 oligodendrogliomas (33.3%), and 1 of 3 ependymomas (33.3%) showed p53-positive nuclei. Cytoplasmic positivity, found in 25 astrocytomas, was always associated with nuclear positivity. Some p53-positive nuclei were seen in 16.7% of the non-gliomatous tumours, but in all cases p53 positivity was seen in less than 1% of the nuclei. The patients with astrocytomas containing more than 5% p53-positive nuclei were younger (mean 27.3 years) (p = 0.016) and their tumours larger in diameter (mean 4.4 cm) (p = 0.05) than those with p53-negative astrocytomas (mean 41.0 years and mean 3.3 cm, respectively). In p53-positive (> or = 1% of nuclei) grade IV astrocytomas, survival time was significantly shorter (mean 7.2 months) than in p53-negative grade IV astrocytomas (mean 15.5 months (p = 0.024). The results indicate frequent p53 expression in intracranial tumours, especially in gliomas. The association of p53 positivity with young age, larger tumour size, and poor prognosis in high-grade astrocytomas suggests that p53 may be involved in the development of more aggressive types of intracranial tumours. According to these results, p53 immunohistochemical positivity may serve as a prognostic marker in high-grade astrocytomas.

Adult↗
PubMed1994

p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke.

Primary lung carcinomas often carry mutations in the p53 tumor suppressor gene. Most of these mutations alter the conformation of the p53 protein into a more stable phenotype that makes it immunohistochemically detectable. Asbestos is a carcinogen that can cause deletions in chromosomes and possibly also gene mutations. In this study we examined 70 primary lung carcinomas for p53 protein accumulation using a polyclonal antihuman p53 antibody, CM-1. Patients were interviewed about their occupational and smoking history and classified according to their anamnestical asbestos exposure. Presence of asbestos bodies (AB) was evaluated from histologic samples of peripheral nontumorous lung tissue using both 5-microns-thick sections stained with Perls' iron and 30-microns-thick unstained sections. Abnormal accumulation of p53 protein was found in 36 tumors (51%), more often in patients exposed to asbestos than in patients without exposure (67% versus 40%, p = 0.027). Significant association was also noticed between the accumulation of p53 and the asbestos content of lung tissue: 35% of the p53-positive patients had more than one AB/cm2 compared with 14% of p53-negative cases (p = 0.046). Patients with strongly p53-positive tumors were heavier smokers (57.2 +/- 38.2 pack-years) than patients with p53-negative or lightly positive tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings indicate that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53.

Aged↗