[Oncoplastic breast surgery for the management of ductal carcinoma in situ]. / Place de l'oncoplastie dans la prise en charge des carcinomes canalaires in situ.

DCIS (Ductal carcinoma in situ) constitutes 15,2% of breast cancers. Conservative surgery coupled with adjuvant radiotherapy is often recommended. The rate of revision surgery is high, from 30 to 60%. The concern is a high quality resection within clear margins with a satisfactory aesthetic result. The objective of this review is to precise the place of oncoplastic surgery in DCIS care. Among risk factors of recurrence, tumoral invasion of surgical margins is capital. In histology, clear margins usually adopted for DCIS are 2mm, even though there is no international consensus. Recent studies show that a 10mm limit would be better. Aesthetic damage caused by surgery, often increased by radiotherapy, has a negative impact on women quality of life: oncoplastic surgery may minimize it. Techniques of plastic surgery, arranged into level 1 and 2, allow pushing back conservative treatment limits by removing a larger tumor with clear margins. Often used in invasive cancers, few data exist regarding oncoplastic surgery and DCIS. It allows to increase the dimensions of surgical resection by 20% and to decrease positive margins significantly therefore the rate of revision surgeries. Patients are satisfied with it. Specific indications need to be clarified according to age, size and "comedonecrosis" presence. Oncoplastic surgery should be developed in DCIS specific care.

Proteomic analysis of Arabidopsis thaliana (L.) Heynh responses to a generalist sucking pest (Myzus persicae Sulzer).

Herbivorous insects can cause severe cellular changes to plant foliage following infestations, depending on feeding behaviour. Here, a proteomic study was conducted to investigate the influence of green peach aphid (Myzus persicae Sulzer) as a polyphagous pest on the defence response of Arabidopsis thaliana (L.) Heynh after aphid colony establishment on the host plant (3 days). Analysis of about 574 protein spots on 2-DE gels revealed 31 differentially expressed protein spots. Twenty out of these 31 differential proteins were selected for analysis by mass spectrometry. In 12 of the 20 analysed spots, we identified seven and nine proteins using MALDI-TOF-MS and LC-ESI-MS/MS, respectively. Of the analysed spots, 25% contain two proteins. Different metabolic pathways were modulated in Arabidopsis leaves according to aphid feeding: most corresponded to carbohydrate, amino acid and energy metabolism, photosynthesis, defence response and translation. This paper has established a survey of early alterations induced in the proteome of Arabidopsis by M. persicae aphids. It provides valuable insights into the complex responses of plants to biological stress, particularly for herbivorous insects with sucking feeding behaviour.

A fungal biofilm reactor based on metal structured packing improves the quality of a Gla::GFP fusion protein produced by Aspergillus oryzae.

Fungal biofilm is known to promote the excretion of secondary metabolites in accordance with solid-state-related physiological mechanisms. This work is based on the comparative analysis of classical submerged fermentation with a fungal biofilm reactor for the production of a Gla::green fluorescent protein (GFP) fusion protein by Aspergillus oryzae. The biofilm reactor comprises a metal structured packing allowing the attachment of the fungal biomass. Since the production of the target protein is under the control of the promoter glaB, specifically induced in solid-state fermentation, the biofilm mode of culture is expected to enhance the global productivity. Although production of the target protein was enhanced by using the biofilm mode of culture, we also found that fusion protein production is also significant when the submerged mode of culture is used. This result is related to high shear stress leading to biomass autolysis and leakage of intracellular fusion protein into the extracellular medium. Moreover, 2-D gel electrophoresis highlights the preservation of fusion protein integrity produced in biofilm conditions. Two fungal biofilm reactor designs were then investigated further, i.e. with full immersion of the packing or with medium recirculation on the packing, and the scale-up potentialities were evaluated. In this context, it has been shown that full immersion of the metal packing in the liquid medium during cultivation allows for a uniform colonization of the packing by the fungal biomass and leads to a better quality of the fusion protein.

[Placenta accreta: can prenatal diagnosis be performed? Ultrasound and MRI interests. About 27 cases]. / Placenta accreta : peut-on faire le diagnostic en anténatal ? Apport de l'échographie et de l'IRM. À propos de 27 cas.

OBJECTIVES: To list ultrasonography signs identified when a placenta accreta is suspected. Secondary objectives are to analyze the relevance of diagnosis with ultrasonography and magnetic resonance imaging, and to know diagnosis circumstances in order to identify main risk factors. PATIENTS AND METHODS: We present a monocentric retrospective study. All the cases of placentas accreta, observed from 2005 to 2010 at Lille University Hospital (France), have been included. RESULTS: Twenty-seven patients had a placenta accreta during this period. There was an antenatal suspicion for 22 cases and 21 were confirmed after delivery. Six cases were discovered per-partum. Diagnosis was suspected after metrorrhagia for 41% of women. In case of antenatal diagnosis, 100% of the patients had an anterior placenta praevia and an uterine scare. Fifty percent of the placentas accreta diagnosed per-partum were posterior. The most frequently ultrasonography signs are "intra-placental lacuna" (85.7%), "abnormal vascularization" (71.4%), "loss of normal hypoechoic retroplacental myometrial zone" (66.7%), "irregularity of the vesical wall" (66.7%). Sensibility of ultrasonography screening is 78%. Twenty-one magnetic resonance imaging examinations executed secondarily confirmed the diagnosis in 66.7% of the cases. DISCUSSION AND CONCLUSION: Ultrasonography is a relevant exam for the diagnosis of placenta accreta. Posterior placenta should not be forsaken. Anterior placenta praevia in multiparous patients with a uterine scare should be a warning.

Epidemic Lymphogranuloma venereum during epidemics of crack cocaine use and HIV infection in the Bahamas.

BACKGROUND: Since the early 1980s, the Bahamas has experienced sequential epidemics of freebase/crack cocaine use, genital ulcer-inguinal adenopathy disease (GUD), and heterosexual HIV infection. GOAL: To prospectively define the etiology of GUD in patients at the Princess Margaret Hospital during outbreaks of crack cocaine use, GUD, and HIV infection in the Bahamas. STUDY DESIGN: In Nassau, 47 consecutive patients with GUD underwent serologic testing for syphilis and for infections with HIV, herpes simplex virus type 2 (HSV-2), and Chlamydia trachomatis. Genital ulcer specimens were tested by culture and/or polymerase chain reaction (PCR) assay for Haemophilus ducreyi; by PCR and/or antigen assay for HSV; and by PCR for C trachomatis. Lymph node aspirates were tested by PCR for C trachomatis and H ducreyi. RESULTS: Twenty patients (43%) had HIV infection; eight had lymphogranuloma venereum (LGV), confirmed by PCR detection of C trachomatis sequences consistent with the L2 serovar; and nine others had possible LGV, on the basis of serum microimmunofluorescent C trachomatis antibody titers > or =256. Inguinal lymphadenopathy or bubo was present in 15 of 17 patients, who thus met the laboratory criteria for definite or possible LGV, and in 7 of 30 who did not meet such laboratory criteria (P < 0.001). Thirteen patients had confirmed genital herpes, seven had confirmed chancroid, and four had probable or possible primary syphilis. CONCLUSIONS: The epidemics in the Bahamas of crack use, heterosexual HIV infection, and GUD apparently included epidemic transmission of LGV.

Reduction of contamination risks during clinical studies with technegas.

During patient studies with the Technegas equipment in our department, we regularly detected small to considerable contaminations of the operator and in the area surrounding the apparatus. These contaminations were found to be of different origin: residual activity in the tubing from the apparatus to the patient which diffuses after deconnection, residual activity and small particles of the destroyed carbon crucible in the apparatus which are dispersed during opening of the door of the gas preparation chamber, leakage at the patient site during studies in uncooperative patients and a dysfunctioning valve inside the apparatus. To reduce the contamination risks, we made some adaptations to the apparatus. In the first place, the dysfunctioning valve was replaced. In addition, a powerful air exhaust pump with an efficient filter was installed. It was connected with (1) a newly installed transparent box in front of the door of the gas preparation chamber, (2) a dome on a flexible arm which can be positioned above the patient's face during the examination and (3) a nipple on which the mouthpiece can be placed after the study. After these adaptations, a study showed the absence of measurable contamination on the clothing of the personnel handling the apparatus. Occasionally, considerable contamination was still measured on the gloves worn during filling of the carbon boat with generator eluate, but only small contaminations (up to 9.25 kBq) were measured on the mouthmask worn by the operator during administration of the Technegas. This results in a maximum effective dose equivalent from activity deposited in the lungs of 0.008 microSv per study. The total body dose of the operator from external radiation for one Technegas examination was determined to be 2 microSv. The highest dose rate was measured during filling of the crucible (0.2 mSv/h).

Warfarin-fluconazole. II. A metabolically based drug interaction: in vivo studies.

Consistent with expectations based on human in vitro microsomal experiments, administration of fluconazole (400 mg/day) for 6 days to six human volunteers significantly reduced the cytochrome P450 (P450)-dependent metabolic clearance of the warfarin enantiomers. In particular, P4502C9 catalyzed 6- and 7-hydroxylation of (S)-warfarin, the pathway primarily responsible for termination of warfarin's anticoagulant effect, was inhibited by approximately 70%. The change in (S)-warfarin pharmacokinetics caused by fluconazole dramatically increased the magnitude and duration of warfarin's hypoprothrombinemic effect. These observations indicate that co-administration of fluconazole and warfarin will result in a clinically significant metabolically based interaction The major P450-dependent, in vivo pathways of (R)-warfarin clearance were also strongly inhibited by fluconazole. 10-Hydroxylation, a metabolic pathway catalyzed exclusively by P4503A4, was inhibited by 45% whereas 6-, 7-, and 8-hydroxylations were inhibited by 61, 73, and 88%, respectively. The potent inhibition of the phenolic metabolites suggests that enzymes other than P4501A2 (weakly inhibited by fluconazole in vitro) are primarily responsible for the formation of these metabolites in vivo as predicted from in vitro kinetic studies. These data suggest that fluconazole can be expected to interact with any drug whose clearance is dominated by P450s 2C9, 3A4, and other as yet undefined isoforms. Overall, the results strongly support the hypothesis that metabolically based in vivo drug interactions may be predicted from human in vitro microsomal data.

Infection with Chlamydia trachomatis lymphogranuloma venereum serovar L1 in homosexual men with proctitis: molecular analysis of an unusual case cluster.

Among 767 rectal isolates of Chlamydia trachomatis obtained from men over the period 1981-1991, 7 were found to be a rare lymphogranuloma venereum serovar, L1. These isolates were from rectal specimens taken from five male patients in 1982-1983. Six of the seven isolates were available for DNA sequencing studies. All six of these isolates shared the same DNA sequence in the major outer membrane protein (MOMP) gene variable domains and had different MOMP sequences than did the prototype L1, L2, and L3 strains, suggesting a point source outbreak. All five patients infected with serovar L-1 were homosexual men who had symptomatic proctitis characterized by rectal pain, discharge, tenesmus, abnormalities seen on anoscopy, and leukocytes seen on gram stains of rectal specimens. We conclude that an unrecognized point source outbreak of the rare chlamydial L1 serovar occurred among homosexual men in Seattle in 1982-1983, and that the clinical manifestations of L1 infection may be less severe than those of L2 infections.

Brain abscess following marrow transplantation: experience at the Fred Hutchinson Cancer Research Center, 1984-1992.

The etiology of brain abscess in patients undergoing marrow transplantation at the Fred Hutchinson Cancer Research Center in Seattle was assessed in a retrospective review. Fifty-eight patients with histology- or culture-proven brain abscess diagnosed between January 1984 and March 1992 were identified. A fungus was isolated in 92% of cases. Aspergillus species were the most prevalent fungi (58% of cases), and Candida species were second in frequency (33%); sporadic cases were caused by Rhizopus, Absidia, Scopulariopsis, and Pseudallescheria species. Bacteria were involved in fewer than 10% of cases. There was no appreciable variation from year to year in the incidence of brain abscess over this period. Aspergillus brain abscess was associated with concomitant pulmonary disease (87% of cases), whereas candida brain abscess often occurred in association with fungemia (63% of cases) or neutropenia (63%). Mortality was high (97%); the risk of death was unrelated to etiology or therapeutic regimen. Since the etiology of brain abscess in patients undergoing marrow transplantation is primarily fungal, the development of better antifungal therapeutic and/or prophylactic modalities is warranted.

Diagnosis of Chlamydia trachomatis urethritis in men by polymerase chain reaction assay of first-catch urine.

To determine the accuracy of a recently developed polymerase chain reaction (PCR) urine assay to detect Chlamydia trachomatis urethral infection in men, we obtained urethral swabs and first-catch urine from 365 men attending a sexually transmitted diseases clinic. Thirty-three (9%) of the 365 men were infected with C. trachomatis as defined by urethral culture. Thirty-two of the 33 men with culture-positive urethral swabs also had PCR-positive urine assays. Of 332 patients with culture-negative urethral swabs, 325 had PCR-negative urine. Compared with chlamydia culture of urethral specimens, PCR assay of urine samples thus had a sensitivity of 97% and a specificity of 98%. The positive predictive value of the urine PCR assay was 82%, and the negative predictive value was 99%. Analysis of discrepant results indicated that six of seven PCR-positive, urethral culture-negative patients probably had chlamydial urethritis. All six patients had symptoms of urethritis and had either a positive urethral swab PCR or a positive urine PCR with a different amplification target. After resolution of discrepant results, (defining true positives as the 33 culture-positive patients and the 6 PCR-positive, culture-negative patients just described), the sensitivity and specificity of culture were 85% (33 of 39) and 100% (326 of 326), respectively. The revised sensitivity and specificity of PCR were 97% (38 of 39) and 99.7% (325 of 326), respectively. We conclude that this urine PCR assay provides a highly sensitive, noninvasive alternative method for the detection of C. trachomatis urethral infection in high-risk men attending a sexually transmitted diseases clinic. This assay could greatly facilitate the testing of larger numbers of male patients for chlamydial infection and should be studied in other settings.

Diagnosis of Chlamydia trachomatis endocervical infections by a commercial polymerase chain reaction assay.

We evaluated a prototype polymerase chain reaction (PCR)-based assay for Chlamydia trachomatis developed by Roche Molecular Systems to detect endocervical infection in women. Of 587 endocervical samples obtained from women attending the Harborview Medical Center sexually transmitted diseases clinic, 58 (10%) were positive for C. trachomatis by cell culture. Compared with culture, the PCR method had a sensitivity of 88% (51 of 58) and a specificity of 99.2% (525 of 529). The positive and negative predictive values were 92.7% (51 of 55) and 98.7% (525 of 532), respectively. After resolution of discrepant results whereby true positives were considered to be either culture-positive patients (58 patients) or culture-negative patients positive upon PCR analysis using both plasmid- and major outer membrane protein-based primers (4 patients), the resolved sensitivities of the PCR and culture were 89 and 93%, respectively. We subsequently performed a second analysis of 362 women, comparing the proposed commercial PCR assay from Roche Molecular Systems with chlamydia cultures. Thirty (8%) women were infected with C. trachomatis. Compared with culture, the assay had a sensitivity of 60% (18 of 30) and a specificity of 99% (328 of 332). Repeat PCR assay done 2 to 5 days later subsequently yielded positive results for 7 of 11 PCR-negative samples from culture-positive women. We conclude that the Roche Molecular Systems PCR assay provides highly specific results compared with culture in a high-risk population of women. Further study is needed, however, to more clearly define the sensitivity of the PCR assay in detecting endocervical C. trachomatis infection in women and to identify factors that may compromise sensitivity.

Invasive Haemophilus influenzae infections in older children and adults in Seattle.

We recently saw two unusual manifestations of Haemophilus influenzae infection in adults in the Seattle area: fulminant sepsis in an otherwise-healthy man and three episodes of bacteremia in a woman with chronic liver disease. We retrospectively identified 79 bacteremic and 40 non-bacteremic cases of invasive H. influenzae infection developing in patients > or = 9 years of age between 1 January 1980 and 31 December 1990. The most common clinical presentations among patients with bacteremia included pneumonia (52%), septicemia (27%), meningitis (8%), gynecologic infection (5%), and epiglottitis (5%). Underlying illnesses were common in these patients, and overall mortality was 35.5%. Factors associated with mortality included underlying neurological disease, polymicrobial bacteremia, and advanced age. The clinical presentations of the 40 patients without bacteremia included soft-tissue abscesses (45%), lung abscesses (18%), peritonitis (13%), meningitis (8%), gynecologic infection (8%), epididymitis (5%), mastoiditis (3%), and osteomyelitis (3%). Thus H. influenzae disease has a variety of presentations and is associated with significant mortality in older children and adults. Further study is required to determine whether widespread administration of H. influenzae type b conjugate vaccine to infants will alter the development of subsequent disease in later life.

Cytomegalovirus-induced hemorrhagic cystitis following bone marrow transplantation.

Cytomegalovirus (CMV) is a common cause of morbidity and mortality following bone marrow transplantation but has not been demonstrated to cause hemorrhagic cystitis in this setting. We describe a patient who developed gross hematuria and lower abdominal pain 47 days after bone marrow transplantation was performed. Subsequently, CMV was detected in bladder endothelial cells with use of monoclonal antibody staining that was specific for the virus. No other cause for the patient's hemorrhagic cystitis was discovered. The gross hematuria and pain persisted until the patient received intravenous ganciclovir. This case demonstrates that CMV-induced hemorrhagic cystitis can occur following bone marrow transplantation and may respond to antiviral therapy.

Bordetella bronchiseptica pneumonia and bacteremia following bone marrow transplantation.

Bordetella bronchiseptica is a frequent cause of respiratory infections in animals but rarely causes disease in humans. We describe a patient with B. bronchiseptica pneumonia and bacteremia that developed following bone marrow transplantation. B. bronchiseptica infection persisted despite antimicrobial therapy and may have progressed because of the combined effects of the patient's underlying immunosuppression and the antimicrobial antagonism between doxycycline and ciprofloxacin.