Stage IV breast cancer: a population-based study about prognostic factors according to HER2 and HR status.

We aim to describe trends in net survival (NS) and to assess the prognostic factors among women with de novo metastatic breast cancer (MBC) according to human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were provided by the Côte-d'Or breast cancer registry. NS was described using the Pohar Perme estimator and prognostic factors were investigated in a generalised linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2 months, 1- and 5-year NS were 76% and 26% respectively. The survival trend in patients with HER2-positive tumours who did not receive trastuzumab was similar to that in women with triple-negative tumours. A higher relative excess risk of death by cancer was observed for high-grade tumours [RER, relative excess rates = 1.76 (95% CI, confidence intervals: 1.17-2.62) for Scarff Bloom Richardson grade 3 vs. 1 + 2], while a lower risk was observed for luminal tumours [RER = 0.49 (95% CI: 0.27-0.89)] and HER2-positive tumours treated with trastuzumab [RER = 0.28 (95% CI: 0.14-0.59)], both compared with triple-negative tumours. Surgery of the primary tumour was associated with better survival [RER = 0.43 (95% CI: 0.28-0.68)]. With half of the women dead before 29 months, stage IV breast cancer still has a bleak outlook. Progress should continue with new target therapies for both HR and HER2 receptors.

A retrospective study of the prescribing and outcomes of tyrosine kinase inhibitors in chronic myeloid leukaemia over a period of more than 10 years.

WHAT IS KNOWN AND OBJECTIVE: Since their introduction, tyrosine kinase inhibitors (TKIs) have been increasingly used in clinical practice. We describe the prescribing and the clinical and biological consequences of two such inhibitors, imatinib and erlotinib, in patients with chronic myeloid leukaemia (CML) in a practice setting over a period of more than 10 years. METHODS: All patients who received at least one TKI for chronic phase CML between 2001 and 2012 in our university hospital were included in the study. RESULTS AND DISCUSSION: Of the 139 patients, with a median age of 57 years, who were surveyed, imatinib and nilotinib were prescribed as the first TKI in 131 (94%) and 8 (6%) patients, respectively. With a median follow-up of 6 years, 342 treatment modifications were observed: 113 (33%) increased doses, 109 (32%) decreased doses, 89 (26%) TKI changes, 14 (4%) definitive discontinuations, 13 (4%) temporary discontinuations and 4 (1%) additions of IFN-α. The main reasons for the 342 treatment modifications were adverse events (n = 112, 33%), long-term optimal response (n = 58, 17%) and failure (n = 57, 17%). Eighty-five (61%), 31 (22%), 18 (13%) and 5 (4%) patients had no, 1, 2 and 3 TKI changes, respectively. Imatinib was the most prescribed TKI (75%). Adverse events resulting in treatment modifications occurred in 18% of patients for imatinib, 49% for nilotinib and 41% for dasatinib (P < 0·001). Median time to TKI change whatever the reason was >50 months (not achieved) for imatinib, 22 months for nilotinib and 27 months for dasatinib (log-rank test, P < 0·001). WHAT IS NEW AND CONCLUSION: Imatinib was the most prescribed TKI both in the first and in subsequent therapeutic lines for chronic phase CML. Our study showed a very good efficacy-safety profile for imatinib at a median follow-up of 6 years in an unselected French population.

Short course of immune-suppressive doses of prednisolone, evaluated through a prospective double-masked placebo-controlled clinical trial in healthy Beagles, is associated with sustained modifications in renal, hydration, and electrolytic status.

OBJECTIVE: To investigate the effects and duration of orally administered prednisolone on renal function evaluated by glomerular filtration rate (GFR) determination and creatinine (Cr) and symmetric dimethylarginine (SDMA) concentrations as well as on urinalysis, electrolytes, and hydric status in healthy dogs. ANIMALS: 14 healthy Beagles. PROCEDURES: In this prospective double-masked placebo-controlled study, dogs were randomized after baseline evaluation to receive a 7-day course of either prednisolone (1.5 to 2.0 mg/kg, PO, q 12 h) or a placebo. A repeated-measure design was performed, each dog participating in 4 successive sampling sessions. Clinical data, systolic blood pressure, CBC, and biochemical analyses including serum SDMA concentration, GFR determination, urine output quantification, and complete urinalysis were performed for all dogs the day before (D0) and at the end of steroid administration (D7) as well as 2 weeks (D21) and 4 weeks (D35) after the end of treatment. RESULTS: At D7, when compared with baseline, GFR increased significantly in treated dogs, whereas creatinine and SDMA concentrations decreased significantly. GFR and Cr but not SDMA modifications persisted significantly at D21. None of the variables differed significantly from baseline at D35. The OR of presenting an albumin band on urine electrophoresis was 2.4 times as high in treated versus control dogs (OR, 36; 95% CI, 1.8 to 719.4; P = 0.02). CLINICAL RELEVANCE: A short-term course of immune-suppressive prednisolone treatment in healthy dogs leads to a sustained but reversible renal hyperfiltration state. Modification in electrolytic variables can affect the clinical interpretation of blood work in such patients.

Different zeolite systems for colon cancer therapy: monitoring of ion release, cytotoxicity and drug release behavior.

Three types of oral administrated micronized zeolites [ZSM-5, zeolite A and Faujasite NaX (ZSM-5, ZA and ZX, respectively)] were prepared as anticancer 5-fluorouracil (5-Fu) delivery systems for colon cancer treatment. They were prepared by economically widespread and cheap natural resource, kaolin, at low temperatures, using microwave advanced tool. The obtained powders were characterized by XRD, SEM/EDX and BET; meanwhile, their degradation was investigated in two gastric fluids; FaSSGF (pH 1.6) and FeSSGF (pH 5), through concentration measurement of their solution disintegrated elemental constituents of Na+, Al3+ and Si4+ ions. Also, the processes of drug release and mechanism in both solutions were investigated. Moreover, the inhibition action of 5-Fu-free and 5-Fu-conjugated zeolites on colon cancer cells (CaCo-2) was estimated. The results showed that, the prepared zeolites possessed high surface areas of 526, 250, and 578 m2/g for ZSM-5, ZA and ZX, respectively. Although, zeolite structures seemed significantly stable, their frameworks seemed more likely reactive with time. The ions and drug release for zeolites occurred in successively two stages and found to be pH dependent, where the drug and zeolite ions were significantly of higher values in the more acidic media of the gastric solution (pH 1.6) than those of the mild acidic one (pH 5). The obtained activity indicated no cytotoxic affinity for all the prepared zeolite types. Accordingly, the synthesized zeolite frameworks are proposed to be of strong potential drug delivery vehicle for the treatment of gastrointestinal cancer.

Isolation and molecular characterization of Mycoplasma spp. in sheep and goats in Egypt.

BACKGROUND AND AIM: Different species of Mycoplasma are associated with many pathological problems in small ruminants including respiratory manifestation, this problem results in significant losses, especially in African countries. This study aimed to (I) study some epidemiological aspects of Mycoplasma species infections in Egyptian sheep and goats at Giza Governorate, (II) diagnosis of Mycoplasma species affections using bacterial isolation and identification, (III) apply the polymerase chain reaction (PCR) for typing of different Mycoplasma species, and (IV) illustrate the phylogenetic tree for the isolated Mycoplasma species and other species from GenBank using the purified PCR product. MATERIALS AND METHODS: A total of 335 samples were collected from sheep and goats from Giza Governorate in Egypt as 142 nasal swabs from clinically affected animals, 167 pneumonic lungs, 18 samples from tracheal bifurcation, and 8 samples by bronchial wash were cultured on pleuropneumonia-like organisms (PPLOs) media for cultivation of Mycoplasma species. PCR and sequencing and phylogenetic analysis were adopted to identify and classify the isolated Mycoplasma species. RESULTS: A total of 24 Mycoplasma isolates were isolated on PPLO media, identified by biochemical tests, and confirmed and typed by PCR using specific primers. 10 isolates were confirmed as Mycoplasma arginini, four isolates as Mycoplasma ovipneumoniae by PCR, and 10 isolates as undifferentiated Mycoplasma species. A purified isolate of M. arginini and M. ovipneumoniae was sequenced and phylogenetic analysis was illustrated. CONCLUSION: M. arginini and M. ovipneumoniae are prevalent in Egyptian sheep and goats. Further studies on M. arginini are required due to its high frequency of isolation from pneumonic sheep and goats and also from animals suffer from different respiratory manifestations.

Synthesis, Biological Evaluation and Docking Analysis of Some Novel Quinazolin Derivatives as Antitumor Agents.

Different acid chlorides (2a-d) reacted with anthranilic acid to produce 2-substituted-3, 1-benzoxazin-4-one (3a-d) which was used as starting material to synthesize some condensed and non-condensed heterocyclic compounds by reaction with nitrogen nucleophiles e.g., hydrazine hydrate, and formamide. Some of the newly synthesized analogues were chosen to evaluate their cytotoxic activity against human carcinoma cell lines (HePG2- MCF7- A549). The docking and the cytotoxic activity results revealed that nearly all of the compounds containing N-phenyl aniline showed significant inhibition for the three cell lines.

A STLV-III related human retrovirus, HTLV-IV: analysis of cross-reactivity with the human immunodeficiency virus (HIV).

A category of viruses has been identified which is related to human immunodeficiency virus (HIV) but is more closely related to a group of simian retroviruses (STLV-III). These viruses named HTLV-IV, LAV-II, or SBL-6669, are prevalent in West-Africa. In this study, we analysed the cross-reactivity at the protein level between HTLV-IV and HIV (HTLV-IIIB). The results indicate that most people infected with HTLV-IV have antibodies that react to the major gag protein of HIV p 24. There is also a high degree of immunologic cross-reactivity between the pol gene products of HIV and HTLV-IV. Among these the endonuclease/integrase is more conserved than the reverse transcriptase. In contrast, the envelope glycoproteins that are the most frequently detected antigens by antibodies from exposed individuals are serotype specific. These data make the env gene products the most interesting antigens for serotype specific diagnosis of human retroviruses infections.

Early detection of streptococcal group antigens in skin samples by latex particle agglutination.

The streptococcal group antigens (A to G) were researched in skin biopsy specimens by a latex agglutination technique using commercial (Slidex Streptokit bio-Mérieux and Streptex Wellcome) and experimental reagents. Twenty-seven patients with obvious cutaneous infections (12 cases of erysipelas, nine cases of cellulitis, and six cases of necrotizing fasciitis) and 27 age- and sex-matched controls were studied. Our preliminary data demonstrated the possibility of an early diagnosis of streptococcal cutaneous infections involving the deep dermis and/or hypodermis. We used a latex agglutination technique that is quite specific and gives a better sensitivity (0.63) than either conventional bacteriologic cultures on needle aspiration or skin biopsy specimens.

Streptococcal cause of erysipelas and cellulitis in adults. A microbiologic study using a direct immunofluorescence technique.

We prospectively studied 42 adult patients with acute dermis and soft-tissue infections (27 with erysipelas and 15 with acute cellulitis) involving the lower limb in all except one case. Streptococcus organisms (groups A, C, D, and G) were researched in skin biopsy specimens by a direct immunofluorescent (DIF) technique using commercially available antibodies. Our results showed that DIF gives a sensitivity of 0.70 for the in situ detection of streptococci in cases of erysipelas and cellulitis. With the obvious contribution of this DIF technique, streptococcal pathogens could be detected in situ and grouped in 19 of 27 cases of erysipelas (group A, 13; group B, 1; group C, 1; and group G, 4) and in ten of 15 cases of cellulitis (group A, 9; group B, 1). Combined data, including conventional cultures, DIF studies, and serologic findings, established that Streptococcus organisms, especially Streptococcus pyogenes (A), were, in nearly all cases, responsible for both erysipelas (26/27 cases) and acute cellulitis (11/15 cases) involving the lower limb in adults.

Evaluation of the microbial safety of a new 1.5 l enteral feeding diet reservoir system.

BACKGROUND & AIMS: Microbial safety is essential during enteral nutrition (EN) as it can be the origin of gastrointestinal symptoms, but can also lead to systemic infections. The use of large-volume diet reservoirs could limit the risk of contamination and reduce nursing time, due to fewer repeated manipulations. The aim of the study was to evaluate in vivo the microbial safety of a new 1.5l enteral feeding diet reservoir system. METHODS: After validation of the study settings under standard laboratory conditions, 86 EN lines with sealed fittings were connected to 1.5l diet reservoirs under hospital/patient conditions. Microbial identification and quantification at different sampling times and points were performed. RESULTS AND CONCLUSIONS: No microbial contamination was observed in the diet reservoirs and in the nutrition lines above the drip chamber, demonstrating the microbial safety of this system. Retrograde contamination of the distal nutrition line end at completion of EN was observed and may be affected by the cumulative time of use of the tube. The contaminating microbial species were essentially bacteria of normal oral and digestive flora.

Anterior chamber concentrations of vancomycin in the irrigating solution at the end of cataract surgery.

PURPOSE: To verify that therapeutic levels of vancomycin were present in the irrigating solution at the end of cataract surgery. SETTING: Service d'ophtalmologie, Université de Limoges, France. METHODS: An irrigating solution that contained 20 mg/L of vancomycin was used in 15 patients having phacoemulsification. Antibiotic concentrations in the phacoemulsification handpiece and in the aqueous humor were measured at the end of surgery. RESULTS: Passage through the phacoemulsifier did not affect antibiotic concentration. In the aqueous humor, after wound closure, the concentration constantly exceeded the minimal inhibitory concentration of the principal gram-positive bacteria responsible for human endophthalmitis. CONCLUSION: Vancomycin added to the irrigating solution used during cataract surgery was found in effective concentrations in the anterior chamber at the end of surgery.

Human vitreous penetration of imipenem.

The purpose of this study was to determine imipenem concentrations in vitreous humor of non-infected human eyes. Ten patients undergoing vitrectomy were infused with a single dose of either 0.5g (5 patients) or 1g (5 patients) of imipenem. Vitreous humor was withdrawn 2 or 4 hours after the end of the infusion. Results differed in relation to the dose. After 0.5g, vitreous levels were stable (approximately 0.20 mg/l), but after 1g they were significantly higher (approximately 2 mg/l). These levels were above the minimum inhibitory concentration of imipenem for 90% (MIC 90) of the main species responsible for endophthalmitis.

[Maternal-infant transmission of the HTLV-1 virus]. / Transmission mère-enfant du virus HTLV-1.

The virus is transmitted horizontally via the bloodstream or sexual intercourse but vertical transmission is also believed to be a major mode of contamination. Between 20 and 25% of children born to seropositive mothers are believed to be infected and more than 90% of mothers whose children are found to be seropositive are themselves infected. If transplacental route appears to be exceptional or poorly documented, transmission by breast-feeding has been proved by virological, experimental and epidemiological arguments and is a major mode of contamination.

[Ocular bacterial infections : present and prospective methods of diagnosis]. / Infections oculaires bactériennes: méthodes di diagnostic actuelles et prospectives.

Bacteriological samples and tests are essentiel for the diagnosis of superficial ocular infections and endophtalmitis. The direct examination and the traditional culture of the samples can be in the futur associated with new diagnostic approach using antigen detection (immunofluorescence, enzyme immunosorbent assays) and genome research by hybridation or better by amplification for Chlamydia and for the most frequent species responsible of endophtalmitis. An original genomic strategy of bacterial endophtalmitis diagnosis was developped.

[Intraocular penetration of ceftriaxone in man. Comparison with other beta-lactamins]. / Pénétration intra-oculaire de la ceftriaxone chez l'homme. Comparaison à d'autres bétalactamines.

The intraocular penetration of a new antibiotic, ceftriaxon, was studied in 30 patients. Serum samples in 29 patients showed an average level of 42 micrograms/ml. Penetration into the aqueous humour flow studied in 28 patients under general anesthesia at one, two, three, four and six hours after the injection. An average level of 0,53 micrograms/ml was found which is 1,25% of average serum level. In 23 patients the dry level in tears averaged 5,75 micrograms/ml (13% of the serum level). In one case of retinal detachment the level in the subretinal fluid was 1,56 micrograms/ml. The kinetics drug secretion in tears was studied in 3 patients without anesthesia every 2 hours until the 16 th to 22 nd hours. Lower levels than those obtained under general anesthesia were obtained. This study shows that ceftriaxon has an intraocular penetration at levels above the minimal inhibitory concentrations for most commun intraocular infection.

[Intraocular penetration of fosfomycin in man and rabbits]. / Etude de la pénétration intraoculaire de la fosfomycine chez l'homme et chez le lapin.

The intraocular distribution of fosfomycin was studied in 32 patients undergoing cataract surgery and or vitrectomy and in 8 rabbits after experimental infection of one eye by Staphylococcus aureus. In subjects perfused with 4 g of fosfomycin, concentrations ranged from 14 to 18.8 mg/l in aqueous humour (AH) and from 8 to 12.5 mg/l in vitreous fluid (VF) between 1 and 6 hours after the end of the perfusion; these levels were higher than MICs for 80-90 per cent of bacteria found in endophthalmitis. In rabbits the concentration in infected eyes with respect to healthy eyes was found to be from 2.5 to 5 times in AH and from 4.9 to 19.2 times higher in VF. Therefore fosfomycin in association with third generation cephalosporins (ceftriaxone) or with new quinolones can be recommended in the prevention and early treatment of endophthalmitis.

[Bacterial dermo-hypodermatitis in adults. Incidence and role of streptococcal etiology]. / Dermohypodermites bactériennes de l'adulte. Incidence et place de l'étiologie streptococcique.

INTRODUCTION: The frequency of bacterial dermohypodermal infections would appear to be increasing in western countries, particularly severe necrotizing forms. PATIENTS AND METHODS: We attempted to determine: (1) the incidence of the two most well-defined forms of bacterial dermohypodermal infections (erysipelas and necrotizing fasciitis) in a retrospective study of hospitalized cases seen over a period of 13 years in the Limoges University Hospital and (2) the role of streptococci as causative agents in bacterial dermohypodermal infections in the adult by collecting bacteriological data in 174 cases of erysipelas and 31 cases of necrotizing fasciitis. RESULTS: This retrospective analysis confirmed that the annual incidence of erysipelas was constantly increasing over the study period (1978-1991) while the annual incidence of necrotizing fasciitis was much lower and more constant. The two incidence curves were not parallel. Bacteriology, detection of streptococci (groups A, B, C or G) in skin specimen was better with direct immunofluorescence (64 p. 100) than with latex agglutination (47 p. 100) or classic culture techniques (28 p. 100) for erysipelas. Streptococci were determined to be the causative agent in 79 p. 100 (137/174) of the cases of erysipelas using at least one of the 3 bacteriological tests and/or serology. Group A streptococci predominated (67 p. 100 of the cases). For necrotizing fasciitis, streptococci was identified with classical culture technique, latex agglutination and/or serology in 12/131 cases (39 p. 100), again with a group A predominance (7 cases). In the other cases, multiple microbial flora (12 cases) were found including Staphylococcus aureus (3 cases) and Serratia liquefaciens (1 case). CONCLUSION: These results show that streptococci (group A predominantly and group G to a lesser extent) were the major, though not exclusive, causative agents in bacterial dermohypodermal infections in the adult, including necrotizing forms.

[Carriage of Staphylococcus aureus. A severity factor of erysipelas?]. / Portage de Staphylococcus aureus. Facteur de gravité de l'érysipèle?

INTRODUCTION: Occasional superinfection or co-infection with Staphylococcus aureus led us to search for S. aureus carriage prospectively in patients with non-necrotizing bacterial dermophypodermitis, in particular erysipelas. PATIENTS AND METHODS: This prospective study included immunocompetent patients with bacterial dermophypodermitis without signs of toxicity or local manifestations suggesting necrotizing fasciitis. Bacteriology tests included: 1) direct immunofluorescence for streptococcus (groups A, C, G) on skin biopsies taken on day 0, 2) samples from the nasal orifices, the intergluteal fold, and potential skin portals for bacteriology culture, and 3) assay of antistreptolysine O and antistreptodornase B on day 0 and 15. RESULTS: The study group included 42 patients (23 females, 19 males, mean age 64 +/- 3.5 yr). In 39 cases (93%) bacterial dermohypodermitis was located on the lower limb with a potential skin portal in 36 cases (86%). Sample culture, direct immunofluorescence or serology findings demonstrated presence of streptococci in 33 cases (79%). Nasal, intergluteal or potential portal were identified in 19 patients (45%) including 16 with demonstrated presence of streptococci. The rate of cure after oral pristinamycin did not vary significantly between carriers (79%) an non-carriers (91%) of Staphylococcus aureus. Drainage of a localized abscess was successful in 5 of 6 patients after initial failure of antibiotic treatment; 4 of them were carriers of S. aureus. CONCLUSION: This prospective study demonstrated that cutaneous-mucosal carriage of Staphylococcus aureus is frequent in patients with non-necrotizing dermohypodermitis. This carriage is not a factor of over-morbidity as shown in this group of infections largely dominated by erysipelas.

[Methi-resistant Staphylococcus aureus in dermatological practice: origin, risk factors and outcome]. / Staphylococcus aureus métirésistant en dermatologie.

BACKGROUND: Increased frequency of methiresistant Staphylococcus aureus (MRSA) in inpatients is a day to day problem. OBJECTIVE: To determine the origin of MRSA, the causes for contamination, and potential complications in a department of Dermatology. PATIENTS AND METHODS: A retrospective study of patients hospitalized in a dermatology department with cutaneous MRSA during 1997-1998. We considered age, type and duration of dermatitis, geographic origin of patients on admission, previous hospitalizations, time between arrival in the ward and positive MRSA, and complications requiring systemic antibiotics. RESULTS: Out of 4579 of our patients, 53 (0.011 p. 100) had positive MRSA. They were on average 70.86 years-old (26 to 97). The most common underlying dermatitis was leg ulcers (30) and foot sores (4). Dermatitis had lasted for more than 1 month in 48 patients. Most of the patients (40) had their MRSA on admission to our ward. Twenty six patients admitted from home had MRSA; only 9 had never been in an hospital. Six patients had diabetes mellitus. Thirty two patients healed with local treatment for their dermatitis. Thirteen patients have had some complications (erysipela 1, osteoarthritis 3, septicemia 2, febrile syndrome 9). DISCUSSION: Most patients with MRSA had leg ulcers or foot sores, confirming liability of chronic wounds to MRSA colonizing. Thirty one out of 40 patients with MRSA at arrival had been previously hospitalized. Hospitalization increases the risk of MRSA contamination. Treatment of MRSA is essentially that of the underlying dermatitis. However, it is still necessary to monitor the lesion for complications.

[Methicilline-sensitive and methicilline-resistant Staphylococcus aureus related morbidity in chronic wounds: a prospective study]. / Etude prospective comparative de la morbidité des Staphylococcus aureus métisensibles et métirésistants dans les plaies chroniques.

OBJECTIVE: Staphylococcus aureus is the most common bacteria responsible for cutaneous infections. Its capacity to adapt has led to the selection of methicilline-resistant strains (MRSA). These strains create specific problems in their management in dermatology (mode of contamination, treatment, added costs, increased nosocomial risks). The objective of our study was to search for morbidity of MRSA in chronic cutaneous wounds in hospital settings and assess the need of systemic antibiotic therapy. PATIENTS AND METHODS: We have conducted a one-year prospective study. All the patients hospitalized in the department with leg ulcers or foot wounds were included. Following local sampling for bacteriological examination, three groups were constituted: methicilline-sensitive patients with staphylococcus aureus (MSSA), methicilline-resistant staphylococcus aureus patients and patients in whom these bacteria were absent. Only the first two groups were compared after studying the past history, clinical description of the wound at the start of the study, results of the infectious bacteriology and of the clinical and bacteriological evolution of the wounds. RESULTS: The two groups studied were similar in number, past history, clinical aspect and therapeutic management. Only malnutrition was more frequent in patients exhibiting MRSA. There was no difference with the evolution of the wounds. CONCLUSION: Our study did not reveal any difference in the morbidity of staphylococcus aureus in the cutaneous wounds whether methicilline sensitive or resistant. Systematic antibiotherapy is not justified in the absence of signs of infection.