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Biomedical subjects

F Kwiatkowski

Publications and source records attributed to F Kwiatkowski.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hematological recovery and peripheral blood progenitor cell mobilization after induction chemotherapy and GM-CSF plus G-CSF in breast cancer.

In order to determine the effect of GM-CSF plus G-CSF in combination in breast cancer patients receiving an effective induction regimen, we compared hematological recovery and peripheral blood progenitor cell (PBPC) mobilization according to colony-stimulating factor (CSF) support. Forty-three breast cancer patients were treated by TNCF (THP-doxorubicin, vinorelbine, cyclophosphamide, fluorouracil, D1 to D4) with CSF support: 11 patients received GM-CSF (D5 to D14); 16 patients G-CSF (D5 to D14) and 16 patients GM-CSF (D5-D14) plus G-CSF (D10-D14). Between two subsequent cycles, progenitor cells were assessed daily, from D13 to D17. The WBC count was similar for patients receiving G-CSF alone or GM-CSF plus G-CSF, but significantly greater than that of patients receiving GM-CSF alone (P<0.001). The GM-CSF plus G-CSF combination led to better PBPC mobilization, with significantly different kinetics (P<0.001) and optimal mean values of CFU-GM, CD34+ cells and cells in cycle, at D15 compared to those obtained with G-CSF or GM-CSF alone. The significantly greater PBPC mobilization obtained with a CSF combination by D15 could be of value for PBPC collection and therapeutic reinjection after high-dose chemotherapies.

Adult↗
PubMed2000

Effects of low-dose neutrons applied at reduced dose rate on human melanoma cells.

Human melanoma cells that are resistant to gamma rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min(-1) or a moderate dose rate of 40 mGy min(-1). The biological effects of neutrons were studied by two different methods: a cell survival assay after a 14-day incubation and an analysis of chromosomal aberrations in metaphases collected 20 h after irradiation. Unusual features of the survival curve at very low dose rate were a marked increase in cell killing at 5 cGy followed by a plateau for survival from 10 to 32.5 cGy. The levels of induced chromosomal aberrations showed a similar increase for both dose rates at 7.5 cGy and the existence of a plateau at the very low dose rate from 15 to 30 cGy. The existence of a plateau suggests that a repair process after low-dose neutrons might be induced after a threshold dose of 5-7.5 cGy which compensates for induced damage from doses as high as 32.5 cGy. These findings may be of interest for understanding the relative biological effectiveness of neutrons and the effects of environmental low-dose irradiation.

Cell Survival↗
PubMed2000

[Assessment of different histoprognosis grading systems for primary ovarian cancer: 100 patients given the same treatment for primary ovarian adenocarcinoma].

BACKGROUND: Numerous grading systems have been proposed for invasive ovarian epithelial carcinoma. But, conflicting reports have been published addressing the value of grade as an independent prognostic factor. DESIGN: The present study investigated the consistency, reproducibility and prognostic value of four different grading systems in a series of 100 homogeneously treated (cytoreductive surgery & platinum based chemotherapy) patient. All the slides were reviewed in a double-blind manner by 3 pathologists, typed according to the WHO and graded. Multivariate assessment of survival time was performed with the Cox model. RESULTS: Population parameters - mean age: 60 years, - stage (FIGO) III & IV 85% - survival: 5 years OS: stage III & IV=22,5%. No significant difference for survival was observed when the patients were classified with any of the 4 grades evaluated. Prognostic factors: age<60 (p<0,001), optimal surgery (p<0,01), n+(p<0,02), necrosis>50% (p<0,04), mitotic count<15MF/10HPF (p<0,03) and vascular invasion (p<0,03). Those 3 parameters were assigned to a new highly relevant grade. At multivariate analysis, it was significantly associated with DFS and OS (p<0,01). CONCLUSION: Our grade is simple, useful for all histologic types, non subjective and reproducible. Further studies are warranted to confirm its clinical utility.

Adenocarcinoma↗
PubMed2000

[Sem: a suitable statistical software adaptated for research in oncology].

Many softwares have been adapted for medical use; they rarely enable conveniently both data management and statistics. A recent cooperative work ended up in a new software, Sem (Statistics Epidemiology Medicine), which allows data management of trials and, as well, statistical treatments on them. Very convenient, it can be used by non professional in statistics (biologists, doctors, researchers, data managers), since usually (excepted with multivariate models), the software performs by itself the most adequate test, after what complementary tests can be requested if needed. Sem data base manager (DBM) is not compatible with usual DBM: this constitutes a first protection against loss of privacy. Other shields (passwords, cryptage...) strengthen data security, all the more necessary today since Sem can be run on computers nets. Data organization enables multiplicity: forms can be duplicated by patient. Dates are treated in a special but transparent manner (sorting, date and delay calculations...). Sem communicates with common desktop softwares, often with a simple copy/paste. So, statistics can be easily performed on data stored in external calculation sheets, and slides by pasting graphs with a single mouse click (survival curves...). Already used over fifty places in different hospitals for daily work, this product, combining data management and statistics, appears to be a convenient and innovative solution.

Clinical Trials as Topic↗
PubMed1999

O(6)-methylguanine-DNA methyltransferase gene (MGMT) expression in human glioblastomas in relation to patient characteristics and p53 accumulation.

Repair of cytotoxic DNA damage by O(6)-methylguanine-DNA methyltransferase (MGMT) is a potentially important factor of chemoresistance to chloroethylnitrosoureas (CENUs), commonly used in the treatment of glioblastoma multiforme (GBM). The value of p53 as a prognostic factor in GBMs remains unclear, but a possible relationship between MGMT gene expression and p53 has been suggested. To further examine these GBM characteristics in vivo, we assessed MGMT gene expression using semi-quantitative RT-PCR and p53 alteration by immuno-histochemistry on a series of 39 GBMs. MGMT gene expression was inversely correlated with age (p < 0.03), consistent with the results of others. Interestingly, tumors from male patients had higher MGMT mRNA amounts than tumors from female patients (p < 0.03). No prognostic implication was observed either for MGMT gene expression or for p53 accumulation. However, MGMT gene expression was significantly lower in p53-altered GBM, regardless of the percentage of positive cells (p < 0.01). Our observation suggests that in human glial tumors, a low level of MGMT gene expression might promote p53 alteration, probably via mutation of its gene. Int. J. Cancer (Pred. Oncol.) 84:416-420, 1999.

Aged↗
PubMed1999

Effect of CO(2) gas warming on pain after laparoscopic surgery: a randomized double-blind controlled trial.

BACKGROUND: Previous studies have suggested that gas temperature has an influence on postlaparoscopy pain. This trial therefore was conducted to study the effect of gas warming on pain after upper abdominal laparoscopic surgery. METHODS: Patients who underwent laparoscopic cholecystectomy, fundoplication, or Heller's myotomy were included and randomly allocated to receive either warm or cold gas. Primary end point was shoulder tip pain, and secondary end points were subcostal, trocar wound, and visceral pains, as well as other postoperative events. Criteria of pain assessment were the visual analog scale, verbal rating scale, and amount of analgesics. RESULTS: A total of 100 patients were suitable for postoperative evaluation. The groups were well matched. Shoulder tip and subcostal pains were significantly more intense after gas warming (p < 0.05). The three assessment criteria showed the same differences. No difference was observed concerning trocar wound and visceral pains and the other secondary end points. Subdiaphragmatic temperature was not significantly different (34.4 degrees with warming vs. 34 degrees without warming). CONCLUSIONS: Gas warming does not reduce, and probably increases, postoperative shoulder tip and subcostal pains.

Carbon Dioxide↗
PubMed1999

Systematic sequencing of the BRCA-1 coding region for germ-line mutation detection in 70 French high-risk families.

Seventy French high-risk families were screened for germ-line BRCA-1 mutations. The BRCA-1 coding region and the exon-intron boundaries were sequenced, except when pre-screening by PTT revealed a truncated protein in exon 11. Germ-line BRCA-1 mutations were detected in 24% of families. The number of breast and ovarian cancers per family, a relative young age at ovarian cancer diagnosis, and the occurrence of breast and ovarian cancer in the same patient significantly predicted the presence of a BRCA-1 mutation. The low BRCA-1 mutation frequency suggested that some alterations were not detected and some families were probably BRCA-2 or BRCAx carriers.

Adult↗
PubMed1999

[First validation of the French version of the Gastrointestinal Quality of Life Index (GIQLI)].

AIM: Gastrointestinal quality of life index (GIQLI) was initiated in Germany. The aim of this study was to validate its French version (translation). METHODS: The questionnaire includes 36 items asking about symptoms, physical status, emotions, social dysfunction, and effects of medical treatment. The questionnaire has been applied to 615 persons: 335 healthy individuals and 280 patients. Responsiveness and absolute and relative scores were calculated in both groups. Psychometric analysis was done by measuring the validity (convergent and discriminant) and internal consistency. RESULTS: The responsiveness was 93%. The mean score was 126 for healthy individuals and 96 for patients (P < 0.00001). The validity of the questionnaire (both convergent and discriminant) and the internal consistency were demonstrated. Clinical validity was also suggested by the differences between healthy individuals and patients. CONCLUSION: This study allowed the psychometric validation of the French version of GIQLI. This index could be used in France as a reliable method for measuring quality of life related to gastrointestinal diseases.

Adult↗
PubMed1998

Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-alpha therapy.

There is a need for fast and sensitive methods to evaluate the response of patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha) therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome-positive metaphases. We have used interphase FISH (fluorescence in situ hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain reaction) techniques for detection of BCR-ABL-positive cells to measure suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML patients undergoing IFN-alpha treatment. Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph-positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concluded that interphase FISH and competitive RT-PCR provide reliable information on residual tumour burden and response to IFN-alpha in CML patients. These molecular methods may significantly improve the efficiency of residual disease monitoring during IFN-alpha therapy of CML.

Antineoplastic Agents↗
PubMed1998

Primary chemotherapy in breast cancer: correlation between tumor response and patient outcome.

This study focused on the correlation between tumor response and patient outcome in 329 breast cancers treated with primary chemotherapy. There were 141 stage IIIB tumors, including 109 inflammatory carcinomas. Other malignancies (34 IIIA, 99 IIB, 55 IIA) were operable but considered to be too large (> 3 cm) for conservative surgery and received primary chemotherapy to avoid mastectomy. All received the AVCF regimen, comprising 4-week cycles of doxorubicin (30 mg/m2) day 1, vincristine (1 mg/m2) day 1, 5-fluorouracil (5-FU; 400 mg/m2) days 2 through 5, cyclophosphamide (300 mg/m2) days 2 through 5. In 189 cases, methotrexate (15 mg/m2) was added at day 2 and day 3. Patients received 6 cycles, then underwent locoregional treatment (surgery, radiotherapy, or both) according to tumor regression. The response rate was assessed by clinical, mammographic, and echographic examinations: a 50% rate of objective responses were noted, of which 15% were complete responses (tumor shrinkage allowed breast conservation in 68% of patients who had stages II or IIIA). For the whole population studied, median follow-up was 111 months (range, 60- 196). One hundred fifty-seven patients had disease relapse (48 local, 14 contralateral, 95 distant). Kaplan-Meier estimates showed an increased 10-year overall survival for patients in complete response, as compared with noncomplete response: 70% versus 50% (p < 0.03). Complete response to neoadjuvant chemotherapy seems a good prognostic factor.

Adult↗
PubMed1998

Association of N-acetyllactosamine with tumor progression in human breast cancer: a study using a 16 kDa chick embryo lectin.

This study documents modifications in the expression and the cellular distribution of binding sites for a 16 kDa chick embryo lectin (CL16-BS) in breast cancer. This lectin binds preferentially to terminal and penultimate N-acetyllactosamine residues (Galbeta1-4GlcNAc). BS density and distribution, studied by lectin binding followed by indirect immunofluorescence, were compared in normal breast tissues and 45 invasive carcinomas (lobular and ductal). Increased number of fluorescent epithelial cells (ETC+) were observed in normal ducts adjacent to lobular carcinomas and in tumors from both types when compared to normal glands. In ductal carcinomas, a significant diminution of ETC+ percentage was observed in the highest anatomopathological SBR grades: 32.7% in grade III, 80.8% in grade II and 66.5% in grade I (p<0.001). For both lobular and ductal carcinomas, ETC+ percentages were also positively correlated with low versus high MSBR grades (p<0.002). The subcellular distribution of CL16-BS varied according to the tumor type and/or the histological grades. It was mostly membrane-associated in low SBR and MSBR grades (p<0.001 and p<0.01, respectively) and cytoplasm-associated in high grades (p<0.02 and p<0.05). Some of these parameters were also correlated with certain other clinicopathological factors, such as tumor size (p<0.02), high S-phase cell fraction (p<0.04 and p<0.03) and low density estrogen receptors (p<0.05). Diminution in CL16-BS density and cytoplasmic versus membrane localization may be considered as indicators of tumor progression but not of metastasis.

Amino Sugars↗
PubMed1998

Pathology of sporadic breast tumors with LOH at the BRCA1 locus: correlation with histopathological features specific to familial BRCA1 tumors and absence of microsatellite instability.

To investigate the coordinated occurrence of loss of heterozygosity (LOH) at the BRCA1 locus and microsatellite instability (MI) in sporadic breast carcinomas, 56 tumors were analysed for both genetic alterations. The comparison of clinicopathological features with the obtained data revealed that LOH at the BRCA1 locus was significantly correlated with features specific for familial BRCA1 tumors and with absence of hormone receptors. No correlation was found between LOH and MI. These results suggest that sporadic and familial breast tumors, where BRCA1 is altered, could display similar clinicopathological features and that LOH and MI are distinct genetic events in sporadic breast carcinogenesis.

Adult↗
PubMed1998

Loss of heterozygosity of BRCA1, BRCA2 and ATM genes in sporadic invasive ductal breast carcinoma.

The present study was undertaken to analyse the loss of heterozygosity (LOH) of the three genes, BRCA1, BRCA2 and ATM, and their correlation to clinicopathological parameters in sporadic breast cancer. We studied 59 sets of invasive ductal carcinoma, compared to matched normal control DNA. Microsatellite markers intragenic to BRCA1 (D17S1323, D17S1322, D17S855), BRCA2 (D13S1699, D13S1701, D13S1695) and ATM (D11S2179) were simultaneously used. In addition, one marker telomeric to BRCA2 (D13S1694) and four markers flanking ATM were analysed (D11S1816, D11S1819, D11S1294, D11S1818). Thirty-one per cent of the informative cases showed loss of heterozygosity for the BRCA1 gene, 22.8% for BRCA2 gene and 40% for ATM. LOH of BRCA1 correlated with high grade tumors (p=0.0005) and negative hormone receptors (p=0.01). LOH of ATM correlated with higher grade (p=0.03) and a younger age at diagnosis (p=0.03) in our set of tumors. No correlations were detected between BRCA2 LOH and any of the analysed clinicopathological parameters. However, a correlation was detected between allelic loss of the D13S1694 marker, telomeric to BRCA2, and larger tumor sizes and negative estrogen receptors, favoring the hypothesis of the presence of another putative tumor suppressor gene, telomeric to BRCA2, in the 13q12-q14 region. Only 11 tumors had LOH at more than one of the three genes, most of them (6/11) associated LOH of BRCA1 and ATM. One tumor only combined loss of the three genes BRCA1, BRCA2 and ATM.

Adult↗
PubMed1998

[Long-term results of cobalt 60 curietherapy for uveal melanoma].

PURPOSE: To analyze 65 patients with uveal melanomas treated with cobalt plaque therapy with regards to mortality, visual results and complications. PATIENTS AND METHODS: Most of the melanomas were large (T3: 52.5%), with a mean largest dimension of the base of 11 mm, and a mean thickness of 6 mm. Most of the tumors were located in the choroid (95%), with an anterior margin behind the equator (65%), and a posterior margin at less than 3 mm of the disc and/or of the macula (69%). The plaque radiotherapy delivered a mean dose of 95 Gy to the tumor apex, either with a cobalt plaque alone (51 cases), or in association with a ruthenium plaque (14 cases). The mean follow up period was over 8 years. RESULTS: The local control was achieved initially in 86% of the eyes. The estimated melanoma specific survival rate was 83% after 5 years and 74% after 10 years. The main parameter associated with the metastases was the largest dimension of the base (p < 0.01). The eye was retained in 83% of the cases. The probability of keeping a vision better than or equal to 0,1 was 39% after 5 years and 27% after 10 years. The main parameter associated with the visual loss was the tumor size (p < 0.01). The complications included cataract (39%), radiation retinopathy (34%), with maculopathy (19%) and/or papillopathy (13.5%), vitreous hemorrhages (22%), neovascular glaucoma (15%) and retinal detachment (12%). CONCLUSION: These results supported the value of cobalt plaque radiotherapy in the management of uveal melanomas.

Adult↗
PubMed1997

Detection of heterozygous carriers of the ataxia-telangiectasia (ATM) gene by G2 phase chromosomal radiosensitivity of peripheral blood lymphocytes.

In ataxia-telangiectasia (A-T) patients, mutations in a single gene, ATM, result in an autosomal recessive syndrome that embraces a variety of clinical features and manifests extreme radiosensitivity and a strong pre-disposition to malignancy. Heterozygotes for the ATM gene have no clinical expression of A-T but may be cancer prone with a moderate increase in in vitro radiosensitivity. We performed a blind chromosomal analysis on G2-phase lymphocytes from 7 unrelated A-T patients, 13 obligate A-T heterozygotes (parents of the patients), and 14 normal controls following X-irradiation with 1 Gy in order to evaluate this cytogenetic method as a tool for detection of ATM carriers. Both A-T homozygotes and heterozygotes showed significantly increased levels of radiation-induced chromatid damage relative to that of normal controls. These results show that the G2-phase chromosomal radiosensitivity assay can be used for the detection of A-T heterozygotes. In combination with molecular genetic analyses, this test may be of value in studies of familial and sporadic cancers aimed at determination of the potential involvement of ATM mutations in tumor risk or development.

Adolescent↗
PubMed1997

Laparoscopic fimbrioplasty and neosalpingostomy. Experience of the Yaoundé General Hospital, Cameroon (report of 194 cases).

OBJECTIVE(S): To study the fertility results after laparoscopic distal tuboplasty and compare them with the data in the literature. STUDY DESIGN: 194 laparoscopic distal tuboplasties were carried out from May 1992 to May 1994 in the Yaounde General Hospital (Cameroon). The results were analysed according to the age of the patients, the type and duration of infertility, past history of abortion, laparotomy and Chlamydia trachomatis infection, the tube and adhesion scores, surgical procedures and achievement of pregnancy. The fertility rates were calculated according to Cramer's method [11]. The cumulative pregnancy rate curves were drawn up from the life table [12] and compared using the Log-Rank test. RESULTS: 53 patients obtained pregnancy (27.3%) of which 45 were inter-uterine (23.2%) and 8 ectopic (4.1%). Of the 45 intra-uterine pregnancies (IUP), 36 were obtained after fimbrioplasty (33.3%) and 9 after neosalpingostomy (10.5%). The monthly fertility rate at one year was 1.4%. The rate of IUP for tube stages I and II is significantly higher than that for stages III and IV (p<0.001). However the rate of ectopic pregnancies (EP) is proportional to damage to the tubes. Infection with Chlamydia trachomatis, and residual inflammation could have an effect on the achievement of pregnancy. CONCLUSION(S): Our results are similar to those found in the literature. The tube stage thus remains the decisive factor in terms of fertility (Cox: p<0.001). Operative laparoscopy is the best alternative in our countries compared with laparotomy for distal tubal pathology.

Adult↗