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Biomedical subjects

C Hennequin

Publications and source records attributed to C Hennequin.

At least 37 records · Page 2Linked to original sources

[Post-prostatectomy radiotherapy: for which patients and when?].

Biochemical relapse after radical prostatectomy is not exceptional, ranging from 10 to 40% in the literature. To prevent this biochemical failure, adjuvant radiotherapy was proposed to patients with a high risk of relapse. No phase III trial has actually validated this attitude. Best indications for adjuvant irradiation seem to be patients with an extensive extracapsular extension or multiple positive margins. Historical comparisons seems to confer, in these case, a benefit in biochemical control for adjuvant irradiation versus observation. Others authors prefer immediate post-operative irradiation, a delayed treatment, when biochemical relapse has occurred. This attitude has spared some patients irradiation useless. This salvage irradiation lowered the PSA level in 40 to 70% of the cases, but long-term efficiency is obtained only in the case of a low value of the PSA before irradiation. Delayed radiotherapy is, therefore, justified only if a close follow-up is performed, with repeated dosage of PSA. Whatever the case, it is important to differentiate between local and distant relapse: patients with positive nodes at the time of surgery are most likely at risk of distant relapse. It seems that patients with seminal vesicles involvement are also at high risk for distant relapse, but this must be confirmed.

Adenocarcinoma↗

Medullary gnathostomiasis in a white patient: use of immunodiagnosis and magnetic resonance imaging.

A 48-year-old French diplomat presented with a sensory-motor paraparesis of rapid onset, leading to paraplegia. Successive magnetic resonance image scans showed lesions of the thoracic spinal cord that were at different levels from one examination to the next. Specific anti-gnathostome antibodies were detected by means of enzyme-linked immunosorbent assay and Western blot test in both plasma and cerebrospinal fluid. Albendazole treatment prevented disease progression, but only partial regression of the neurologic symptoms was obtained.

Albendazole↗

Impact on survival of surgery after concomitant chemoradiotherapy for locally advanced cancers of the esophagus.

BACKGROUND: To evaluate the results of chemoradiotherapy with or without surgery in locally-advanced esophageal carcinomas (T3 and/or nodal involvement). METHODS: One hundred twelve patients with locally-advanced carcinoma of the esophagus without histologically proven invasion of the tracheobronchial tree or distant visceral metastases were treated with concomitant chemoradiotherapy followed by re-evaluation; surgery was performed or chemoradiotherapy continued, based on tumor regression and the patient's general status. Chemoradiotherapy consisted of concomitant 5-fluorouracil (5FU)(1 g/m(2) day 1-3), cisplatinum (50 mg/m(2) day 1 and 2), and external beam irradiation up to a dose of 40 or 43.2 Gy. After a 4-week rest period, radical esophagectomy or a new cycle of chemoradiotherapy (up to a total dose of 65 Gy) was performed. RESULTS: A complete clinical response was obtained in 25.7% of the patients and a partial response in 45.9%. Fifty patients underwent surgery, but only 38 patients had an esophagectomy. Post-esophagectomy mortality was 5.3%. A complete histologic response rate of 23.7% was obtained. Two- and 5-year survival rates were, respectively, 41.5% and 28.6% for the whole population. According to multivariate analysis, prognostic factors for survival were Karnofsky index, esophagectomy, and response to chemoradiotherapy. Five-year survival for patients who experienced a partial response to radiation and chemotherapy was 49.1% for those who had surgery and 23.5% for those treated without surgery (p = 0.003). There was no obvious benefit for the small number of patients treated surgically after complete response to radiation and chemotherapy. Toxicity, essentially hematologic, was moderate. CONCLUSION: For locally-advanced esophageal carcinomas, esophagectomy, after concomitant chemoradiotherapy, could improve the survival rate, especially for patients who responded partially to the latter.

Adult↗

Analysis of expression of GroEL (Hsp60) of Clostridium difficile in response to stress.

Our laboratory has previously shown that adherence of Clostridium difficile to tissue culture cells is augmented by various stresses and that GroEL, a heat shock protein, serves an adhesive function in this bacterium. In this communication, RT-PCR, SDS-PAGE and immunoblotting were used to study the stress response in C. difficile following heat, acid or osmotic shock, iron deprivation or presence of a subinhibitory concentration of ampicillin in the culture medium. All these stresses increased transcription of groEL and production of GroEL to various degrees. Furthermore, the protein was found in membrane fractions and in the extracellular space after heat stress.

Ampicillin↗

[The role of the laboratory in the diagnosis and prevention of fungal infections].

Fungal infections account for an increasing fraction of nosocomial infections. The laboratory is essential to ascertain the diagnosis. Significant progress has been recently achieved in direct diagnostic tools (better sensitivity of direct examination, development of chromogenic identification media). Diagnostic sensitivity of blood cultures can be increased with the use of special fungal media for culture. However, indirect diagnostic methods remain unsatisfactory, even though some new data support the usefulness of simultaneous detection of circulating antigens and corresponding antibodies. In the future, the contribution of molecular biology techniques could be of great interest, either in the diagnostic (detection of fungal DNA in the serum) or in the identification of species. Last but not least, molecular typing allows a precise monitoring of fungal ecology that could prove useful to the understanding of the physiopathology of infections and to the anticipation and prevention of epidemic outbreaks.

Clinical Laboratory Techniques↗

GroEL (Hsp60) of Clostridium difficile is involved in cell adherence.

Previous results have demonstrated that adherence of Clostridium difficile to tissue culture cells is augmented by various stresses; this study focussed on whether the GroEL heat shock protein is implicated in this process. The 1940 bp groESL operon of C. difficile was isolated by PCR. The 1623 bp groEL gene is highly conserved between various C. difficile isolates as determined by RFLP-PCR and DNA sequencing, and the operon is present in one copy on the bacterial chromosome. The 58 kDa GroEL protein was expressed in Escherichia coli in fusion with glutathione S:-transferase and the fusion protein was purified from IPTG-induced bacterial lysates by affinity chromatography on glutathione-Sepharose. A polyclonal, monospecific antiserum was obtained for GroEL which established by immunoelectron microscopy, indirect immunofluorescence and immunoblot analysis that GroEL is released extracellularly after heat shock and can be surface associated. Cell fractionation experiments suggest that GroEL is predominantly cytoplasmic and membrane bound. GroEL-specific antibodies as well as the purified protein partially inhibited C. difficile cell attachment and expression of the protein was induced by cell contact, suggesting a role for GroEL in cell adherence.

Amino Acid Sequence↗

Sputum itraconazole concentrations in cystic fibrosis patients.

Itraconazole diffusion in sputum was studied in 11 cystic fibrosis patients with allergic bronchopulmonary aspergillosis. There was a high interindividual variability in sputum itraconazole concentration and sputum/serum drug concentration ratio. Three children had sputum drug concentrations before oral administration that were lower than the itraconazole MIC at which 90% of Aspergillus fumigatus strains were inhibited, although their serum drug concentrations were within the therapeutic range.

Adolescent↗

Characterization of a cell surface protein of Clostridium difficile with adhesive properties.

Our laboratory has previously shown that Clostridium difficile adherence to cultured cells is enhanced after heat shock at 60 degrees C and that it is mediated by a proteinaceous surface component. The present study was undertaken to identify the surface molecules of this bacterium that could play a role in its adherence to the intestine. The cwp66 gene, encoding a cell surface-associated protein of C. difficile 79-685, was isolated by immunoscreening of a C. difficile gene library with polyclonal antibodies against C. difficile heated at 60 degrees C. The Cwp66 protein (66 kDa) contains two domains, each carrying three imperfect repeats and one presenting homologies to the autolysin CwlB of Bacillus subtilis. A survey of 36 strains of C. difficile representing 11 serogroups showed that the 3' portion of the cwp66 gene is variable; this was confirmed by sequencing of cwp66 from another strain, C-253. Two recombinant protein fragments corresponding to the two domains of Cwp66 were expressed in fusion with glutathione S-transferase in Escherichia coli and purified by affinity chromatography using gluthatione-Sepharose 4B. Antibodies raised against the two domains recognized Cwp66 in bacterial surface extracts. By immunoelectron microscopy, the C-terminal domain was found to be cell surface exposed. When used as inhibitors in cell binding studies, the antibodies and protein fragments partially inhibited adherence of C. difficile to cultured cells, confirming that Cwp66 is an adhesin, the first to be identified in clostridia.

Adhesins, Bacterial↗

Microsatellite typing as a new tool for identification of Saccharomyces cerevisiae strains.

Since Saccharomyces cerevisiae appears to be an emerging pathogen, there is a need for a valuable molecular marker able to distinguish among strains. In this work, we investigated the potential value of microsatellite length polymorphism with a panel of 91 isolates, including 41 clinical isolates, 14 laboratory strains, and 28 strains with industrial relevance. Testing seven polymorphic regions (five trinucleotide repeats and two dinucleotide repeats) in a subgroup of 58 unrelated strains identified a total of 69 alleles (6 to 13 per locus) giving 52 different patterns with a discriminatory power of 99.03%. We found a cluster of clinical isolates sharing their genotype with a bakery strain, suggesting a digestive colonization following ingestion of this strain with diet. With the exception of this cluster of isolates and isolates collected from the same patient or from patients treated with Saccharomyces boulardii, all clinical isolates gave different and unique patterns. The genotypes are stable, and the method is reproducible. The possibility to make the method portable is of great interest for further studies using this technique. This work shows the possibility to readily identify S. boulardii (a strain increasingly isolated from invasive infections) using a unique and specific microsatellite allele.

Bronchoalveolar Lavage Fluid↗

[Chemotherapy with cisplatinum, carboplatin and 5FU-folinic acid, followed by concomitant chemo-radiotherapy in unresectable esophageal carcinomas].

UNLABELLED: The best chemotherapeutic regimen for advanced carcinoma of the esophagus remains to be determined. We have evaluated a combination of carboplatin, cisplatin and 5FU modulated by folinic acid. Patients. Twenty-seven patients (median age 57 yrs) with an unresectable carcinoma of the esophagus were included in this trial: 9 patients with a local relapse after surgery, 6 patients with a locally advanced (T4) tumor, and 12 patients with metastasis. Treatment schedule. Initial chemotherapy : carboplatine IV d1, AUC4; 5FU: bolus injection of 400 mg/m2 d1, followed by a continuous infusion of 600 mg/m2/24 h, d1 and d2; folinic acid (200 mg/m2) IV, before the 5FU bolus, d1 and d2; cisplatine 80 mg/m2, d3; on d15 and d16, 5FU and folinic acid were repeated with the same schedule. The second cycle began on d28. Concomitant chemo-radiotherapy with 5FU (1,000 mg/m2 d1 to d3), cisplatine (50 mg/m2 d1 and d2) and external irradiation (20 Gy in 10 fractions from d1 to d12) was then performed, for three cycles (until a total dose of 60 Gy). Results. TOXICITY: neutropenia grade 3-4 (32%), thrombopenia grade 3-4 (18%). More important, a lymphopenia (< 500/mm3) was noted in 12 patients (43%). Accordingly, 4 serious infectious complications were observed, with three toxic deaths. Objective response rate: 44% after initial chemotherapy; 75% after chemoradiotherapy, with 8 complete responses (38%). Median survival was 7.4 months, with a one- and two-year survival of 33% and 17,8%, respectively. Conclusion. This association of cisplatin, carboplatin, and 5FU did not offer a better response rate than the classical 5FU-cisplatinum association. But serious infectious complications occurred during the trial. We do not recommended further evaluation of this biplatinum therapy with 5FU in advanced esophageal carcinomas.

Adult↗

Caspase-dependent apoptosis in THP-1 cells exposed to oxidized low-density lipoproteins.

Oxidized low-density lipoproteins (oxLDL) play a critical role in atherogenesis. We investigated the apoptotic process in human monocytic THP-1 cell line, exposed to oxLDL generated by treatment of native LDL either with hypochlorous acid (HOCl), mainly affecting the protein moiety, or with copper sulfate (CuSO(4)), mainly affecting the lipid moiety. After incubation with both types of oxLDL, we observed: (i) microscopy signs of apoptosis in THP-1 cells, (ii) a significant increase of apoptotic cells proportional to LDL protein concentration, either by annexin V or by cell cycle phase analysis with propodium iodide flow cytometry, (iii) a reduction of THP-1 cell apoptosis in presence of the caspase inhibitor Z-VAD.fmk, (iv) the resistance of THP-1 cells apoptosis after PMA-elicited differentiation. In conclusion, HOCl-oxLDL are as potent as Cu-oxLDL to induce high rates of apoptosis in monocytes through a caspase-dependent pathway. Moreover, the resistance of differentiated THP-1 cells to oxLDL-induced apoptosis is compatible with the hypothesis that mature macrophages have prolonged survival and thereby enhance the atherogenic process.

Amino Acid Chloromethyl Ketones↗

Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin's disease: results of the groupe d'études des lymphomes de l'Adulte H89 trial.

The treatment of advanced Hodgkin's disease (HD) with chemotherapy (CTx) alone or combined modality treatments has been controversial. In 1989, we designed a randomized study to compare 2 cycles of CTx to (sub)total nodal irradiation (RTx) as consolidation treatments for patients with stage IIIB/IV HD in complete remission (CR) or good partial response after 6 cycles of CTx. A total of 559 patients were randomized to receive 6 cycles of MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/Adriamycin [doxorubicin], bleomycin, vinblastine) hybrid (n = 266) or ABVPP (n = 267). After induction treatment, 418 patients could be evaluated for the consolidation phase. With a median follow-up of 48 months, the 5-year disease-free survival estimates were 80% for 8 cycles of MOPP/ABV, 82% for 6 cycles of MOPP/ABV plus RTx, 68% for 8 cycles of ABVPP, and 75% for 6 cycles of ABVPP plus RTx (P =.01). The 5-year disease-free survival estimates did not differ between CTx and RTx, 74% and 79%, respectively (P =.07). After MOPP/ABV, the 5-year overall survival estimates did not differ between CTx and RTx, 85% and 88%, respectively (P =.2). After ABVPP, the 5-year survival estimates were 94% for CTx and 78% for RTx (P =.002). These results showed that RTx was not superior to CTx consolidation after doxorubicin-induced CR for patients with advanced HD. Because of the uncertainty of obtaining a prolonged second remission for patients relapsing after CTx and RTx and the possible long-term effects of RTx, we prefer 8 cycles of CTx as standard treatment when a CR has been achieved after 6 cycles.

Adolescent↗

Possible role of catheters in Saccharomyces boulardii fungemia.

Four cases of Saccharomyces boulardii fungemia, a very rare side effect of Saccharomyces boulardii therapy, are reported. The clinical impact of Saccharomyces boulardii infection appeared to be moderate. However, even though organ involvement was never demonstrated, septic shock with no other etiology was observed in one of our patients. All patients had an indwelling vascular catheter. Contamination of the air, environmental surfaces, and hands following the opening of a packet suggests that catheter contamination may have been a source of infection. To prevent catheter contamination it is recommended that packets or capsules of Saccharomyces boulardii be opened with gloves, outside the patient's room.

Adult↗

High-dose-rate brachytherapy for early breast cancer: an ambulatory technique.

PURPOSE: To evaluate tolerance and efficiency of a boost dose delivered by high-dose-rate brachytherapy (HDRB) in conservative treatment of breast cancer. To evaluate the feasibility of brachytherapy on an out-patient basis. METHODS: One hundred and six patients with T1-T2, N0-N1 breast cancers (108 breasts) have been treated with lumpectomy, external irradiation (45 Gy in 5 weeks), and a boost dose on the tumor bed with HDR iridium brachytherapy. Two fractions of 5 Gy were delivered 6 or 24 hours apart. Implantation was done during the lumpectomy (group A: 24 cases) or 3 to 4 weeks after the end of external irradiation (group B: 84 cases). For group B, the application was performed on local anesthesia, and did not require hospitalization. Characteristics of the population were as follows: T1: 77 (71.3%); T2: 31 (28.7%); median tumor size: 1.5 cm; histology: intraductal carcinomas (DCIS): 14 (13%); infiltrative ductal carcinomas (IDC): 84 (77.8%); others: 10 (9.2%). For IDC, surgical margins were found positive in 15 cases, and an extensive intraductal component was present in 22 cases. RESULTS: All ambulatory HDR implants were performed as planned. No immediate toxicity was noticed, except 5 local hematomas. With a median follow-up of 45 months, 5 local relapses were observed (5-year local relapse rate: 5.1%). Only histological grade III was significantly correlated with local relapse. The 5-year disease-free survival and overall survival were respectively 93.8% and 93.3%. Cosmetic result was evaluated in 87 cases, and was good or excellent in 48 cases (63.2%), acceptable in 27 cases, and poor in 5 cases. CONCLUSION: HDRB allows the boost dose to be performed on an out-patient basis. It seems to offer the same local control as other boost techniques for localized breast cancer with acceptable cosmetic results.

Adult↗