Focus on patients receiving long-term antimicrobial treatments for lyme borreliosis: No lyme but mostly mental disorders.

OBJECTIVES: Overdiagnosis of lyme borreliosis leads to unnecessary and increasingly common antimicrobial treatments. We aimed to evaluate patients receiving long-term antimicrobial treatment for lyme borreliosis. METHODS: We included patients referred to a Parisian teaching hospital between January 1st, 2014 and June 30th, 2019, with a presumed diagnosis of lyme borreliosis for which they were treated with antimicrobials for at least 6 months. RESULTS: Fifteen patients were included (11 women and mean age 44 years). The mean antimicrobial treatment duration was 476 days (180-942). The mean number of antimicrobials was 6.8 per patient (1-18). None of the 15 patients had lyme borreliosis. Nine patients were diagnosed with a mental disorder. CONCLUSION: Overdiagnosis and overtreatment of lyme borreliosis put patients at risk of undiagnosed illnesses and multiple adverse effects of unjustified treatments. The clinical management of such patients requires a comprehensive approach including expertise in mental disorders.

Knowledge, actual and potential use of HIV self-sampling testing kits among MSM recruited in eight European countries.

AIM: To describe the knowledge as well as current and potential use of self-sampling kits among men who have sex with men (MSM) and to analyse their preferred biological sample and result communication method. METHODS: We analyse data of MSM of HIV negative or unknown serostatus from an online survey conducted in eight countries (Belgium, Denmark, Germany, Greece, Portugal, Romania, Slovenia and Spain) between April and December 2016. It was advertised mainly in gay dating websites. We conduct a descriptive analysis of the main characteristics of the participants, and present data on indicators of knowledge, use and potential use of HIV self-sampling as well as their preferences regarding blood or saliva sample and face or non-face-to-face result communication by country of residence. RESULTS: A total of 8.226 participants of HIV negative or unknown serostatus were included in the analysis. Overall, 25.5% of participants knew about self-sampling (range: 18.8-47.2%) and 1.1% had used it in the past (range: 0.3-8.9%). Potential use was high, with 66.6% of all participants reporting that they would have already used it if available in the past (range: 62.1-82.1%). Most (78.6%) reported that they would prefer using a blood-based kit, and receiving the result of the test through a non-face-to-face-method (70.8%), even in the case of receiving a reactive result. CONCLUSION: The high potential use reported by MSM recruited in eight different European countries suggests that self-sampling kits are a highly acceptable testing methodology that could contribute to the promotion of HIV testing in this population.

Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP study.

AIM: Improvement of EFS of children older than 3 years with high risk medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment.

High-grade glioma in children under 5 years of age: a chemotherapy only approach with the BBSFOP protocol.

The aim of this study was to evaluate a chemotherapy strategy that avoids radiotherapy in first-line treatment of young children with high-grade glioma. A total of 21 children under 5 years of age received the BBSFOP protocol, comprising seven cycles of three drug pairs (carboplatin/procarbazine, cisplatin/etoposide and vincristine/cyclophosphamide) administered over a 16 month period. Radiotherapy was performed in case of recurrence/progression. Median age at diagnosis was 23 months. Histology was classified as World Health Organisation (WHO) grade III in 13 and grade IV in 8. Of the 13 children with a residual tumour, chemotherapy induced 2 partial responses (PR), 1 minor response (MR) and 1 stable disease (SD) with no recurrent disease. Five-year progression-free survival was 35% and 5-year overall survival was 59%, with a median follow-up of 5.2 years. At the last update, 12 children were alive (10 without radiotherapy). In conclusion, this study shows that an adjuvant chemotherapy first approach is safe and allows radiotherapy to be avoided in selected children.

Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study.

OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.

[Dental anomalies following anticancer chemotherapy]. / Anomalies dentaires après chimiothérapie anticancéreuse.

Chemotherapy administered during childhood may induce dental abnormalities, such as acquired amelogenesis imperfecta, microdontia, hypodontia and altered root morphology. The magnitude of the defect varies according to the cytotoxic agents, the duration of their use and the stage of tooth development at the time of chemotherapy. Patients who received high-dose chemotherapy before the age of 5 are particularly concerned. The dental supervision of these children is based upon three orthopantomograms: the first one has to be performed before starting chemotherapy and will be used as a reference; the second is done soon after the drug therapy in order to evaluate the first consequences; the third is performed after the eruption of all permanent teeth (age 12-13 in average) in order to determine the dental abnormalities. In case of hypodontia, orthodontic treatment must be considered, but it is necessary to take into account the fact that it may increase the risk of root resorption. Preventive dental care is important for these children. It involves meticulous oral hygiene and frequent dental visits to assess and maintain dental health.

One dose ceftriaxone vs. ten days of amoxicillin/clavulanate therapy for acute otitis media: clinical efficacy and change in nasopharyngeal flora.

OBJECTIVE: To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment. METHODS: In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14. RESULTS: Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group. CONCLUSIONS: In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment.

Eradication by ceftriaxone of Streptococcus pneumoniae isolates with increased resistance to penicillin in cases of acute otitis media.

This multicenter, noncomparative, nonrandomized study evaluated the clinical efficacy and safety of ceftriaxone for treating acute otitis media in children following clinical failure of oral antibiotic therapy. Middle-ear fluid samples were collected on day 0 and on day 3, 4, or 5 (day 3 to 5) and were used to test whether ceftriaxone therapy can eradicate Streptococcus pneumoniae isolates with increased resistance to penicillin (MIC >/= 1 mg/liter). At the first visit, on day 0, middle-ear fluid was sampled for bacteriological testing by tympanocentesis or otorrhea pus suction. Patients were administered 50 mg of ceftriaxone/kg of body weight/day, injected intramuscularly once daily, for 3 days. A second sample was collected by tympanocentesis if a pneumococcus isolate for which the MIC of penicillin was >/=1 mg/liter was detected in the day-0 sample and if the middle-ear effusion persisted on day 3 to 5. This second sample was tested for bacterial eradication. One hundred eighty-six children aged 5 months to 5 years, 10 months, with acute otitis media clinical failure were enrolled and treated in this trial. On day 10 to 12, 145 (83.8%) of the 173 patients evaluable for clinical efficacy were clinically cured. Of the 59 patients infected by pneumococci, 36 had isolates for which the MICs of penicillin were >/=1 mg/liter. Of those patients, on day 10 to 12, 32 (88.9%) were clinically cured. Middle-ear fluid samples collected by day 3 to 5 following the onset of treatment with ceftriaxone were sterile for 24 of the 27 (88.9%) patients who were infected as of day 0 by pneumococci for which the MICs of penicillin were >/=1 mg/liter and who were evaluable for bacteriological eradication. On day 10 to 12, 81.4% of S. pneumoniae-infected children and 87.5% of Haemophilus influenzae-infected children were clinically cured. No discontinuation of treatment due to adverse events, particularly due to local reactions at the injection site, were reported. Only 11 adverse events which had doubtful, probable, or possible links with the study treatment were recorded. Both the bacteriologically assessed eradication of pneumococci for which the MICs of penicillin were >/=1 mg/liter and the clinical cure rates demonstrate that ceftriaxone is of value in the management of acute otitis media unresponsive to previous oral antibiotic therapy.

Pathogens isolated during treatment failures in otitis.

OBJECTIVES: A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure. METHODS: The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid. RESULTS: One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14. CONCLUSIONS: Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.

[High dose ifosfamide at 15 g/m2/cycle: a feasibility study in 10 patients]. / L'ifosfamide à hautes doses 15 g/m2/cure. Etude de faisabilité chez 10 patients.

Ifosfamide is one of the most efficient antimitotic in soft tissue sarcoma. To try to find a possible dose-effect, 10 patients with advanced pretraited relapsed soft tissue sarcoma received 15 g/m2/cycle ifosfamide in continuous infusion during 5 days. A pharmacokinetic study was done for 2 patients. All patients received growth factors, ondansetron and 8 clonazepam. Renal toxicity was evaluated after the first and the second cycle. Twenty two cycles were delivered to patients who have been already treated with ifosfamid (10 patients with 15 g/m2 to 54 g/m2, median 27 g/m2) or cis platinum (2 patients). No major renal or neurologic toxicity was observed; only subclinical modifications of urinary enzymes excretion were found. Two patients had visual hallucinations at the end of a cycle and just in the 2 following days; another presented a neuropathy of inferior limbs. Hematological toxicity was very limited. Pharmacokinetic study did not show induction mechanism at this dosage and with this type of administration. So ifosfamide 3 g/m2 during 5 days is feasible. The few level of complications observed is perhaps linked to the daily dose of 3 g/m2 instead of 4 g/m2 or more used in the other studies.

[Atypical decubitus fibroplasia: a recent entity. Apropos of a case of an adolescent girl]. / La fibroplasie atypique de décubitus: une entité récente. A propos d'un cas chez une adolescente.

Atypical decubital fibroplasia (FAD) occurs especially in elderly and physically debilited or immobilized patients. We report one observation which is peculiar due to the patient's young age and its circumstances. The painless mass is situated in hyperpressure areas (shoulder, posterior or lateral chest wall, sacrum). The lesion is situated in the deep subcutis and has ill defined limits; it is characterized by zones of fibrinoid necrosis and fibrosis and a prominent myxoid stroma. The differential diagnoses includes mesenchymatous malignant tumors and non neoplastic fibroblastic proliferations such as proliferative fasciitis and decubitus ulcer. The prominent underlying factor and the initial event contributing to its pathogenesis seems to be ischemia. Although some recurrent cases have been reported, FAD is a benign lesion whose treatment is surgical removal.

Electrical stimulation and swimming performance.

The purpose of the study was to examine the influence of a 3-wk period of electrostimulation training on the strength of the latissimus dorsi m. and the swimming performances of 14 competitive swimmers divided into 7 electrostimulated (EG) and 7 control swimmers (CG). The peak torques registered during the flexion-extension of the arm was determined with the help of an isokinetic dynamometer at different velocities (from -60 degrees.s(-1) to 360 degrees.s(-1)). Performances were measured over a 25-m pull buoy and a 50-m freestyle swim. For EG, a significant increase of the peak torques was measured in isometric, eccentric, and concentric conditions (P < 0.5). The swimming times declined significantly (P < 0.01) by 0.19 +/- 0.14 s, for the 25-m pull-buoy, and by 0.38 +/- 0.24 s, for the 50-m freestyle. For CG, no significant difference was found for any of the tests. For the whole group, the variations of the peak torques, measured in eccentric condition (-60 degrees.s(-1)) were related to the variations of the performances (r = 0.77; P < 0.01). These results showed that an electrostimulation program of the latissimus dorsi increased the strength and swimming performances of a group of competitive swimmers.

Reinfection of liver graft by hepatitis C virus after liver transplantation.

We have investigated hepatitis C virus (HCV) viremia before and after orthotopic liver transplantation (OLT). 38 patients were examined; 16 were anti-HCV positive and 22 anti-HCV negative pre-OLT in a RIBA-2 test (Ortho Diagnostic Systems Inc., Westwood, MA). HCV-RNA was detected using a modified nested polymerase chain reaction in 14/38 and 10/38 patients before and after OLT, respectively. 7 of these 14 subjects who were HCV-RNA positive before OLT were also positive for serum hepatitis B surface antigen. After OLT, six patients became HCV-RNA positive, likely as a result of transfusions, while four developed a probable recurrence of HCV infection. Infection of the liver graft by the same strain of HCV was indeed demonstrated by sequence analysis of a hypervariable domain (in the envelope region) in two cases. This establishes the possibility of HCV recurrence and shows the usefulness of polymerase chain reaction as the only assay currently capable of identifying HCV infection after OLT.

[Relapse prevention in liver transplant patients treated for liver involvement due to hepatitis B virus]. / Prophylaxie des récidives chez les transplantés hépatiques pour atteinte hépatique due au virus de l'hépatite B.

Controversy surrounds the indication of liver transplantation in patients with hepatitis B virus infection. The major problem is the very high risk of infection of the graft. Some investigators have suggested that the presence of HBsAg is a contraindication to liver transplantation. Between February 1975 and December 1990, 178 HBs positive patients were transplanted at Paul Brousse Hospital in Professor H. Bismuth's Department, 137 for post hepatitis cirrhosis and 41 for fulminant hepatitis. Since April 1984 we have decided long term immunoprophylactic therapy for all patients with HBs infection. But only from August 1987 our supply of purified anti HBs immunoglobulin has been adequate to treat all our patients according to the following protocol: 10.000 IU during the peroperative phase, 10.000 IU immediately after intervention, 10.000 IU every day for the first 6 days, 10.000 IU when the anti HBs levels were under 150 IU/l. One hundred thirty-nine patients were treated by this method. 110 cleared HBs antigen from their sera and their liver were biologically and histologically free of B virus infection. 29 patients showed reappearance of HBs antigen in their sera and nearly all of them developed objective, histologically confirmed, graft lesions. These lesions are those of classical infection: acute hepatitis, active chronic hepatitis and cirrhosis. So 79% of patients were successfully treated with a follow up of 45 months to 6 months. We also studied the prognostic factors under treatment. The study shows: in the case of fulminant hepatitis, 93% success versus 77% in post hepatitis cirrhosis; in the case of Delta superinfection, 94% success versus 66% with pure B infection; in the absence of HBVDNA in the patient's sera before transplantation, 92% success versus 20% in the presence of HBVDNA. For a better understanding of the overall results, the two following parameters have to be considered: some patients relapsed after stopping their treatment, some other patients, despite repositivation of HBs antigen in their sera showed a paradoxal good evolution. These considerations enable us to obtain HBVDNA positive patients: 10% success, HBVDNA negative patients: Fulminant hepatitis: 100% success B Delta post hepatitis cirrhosis: 100% success B post hepatitis cirrhosis: 92% success.

Autoregulation of MeWo metastatic melanoma cell growth: characterization of intracellular (FGF, MGSA) and secreted (PDGF) growth factors.

MeWo melanoma cells (clone LC1) secrete a potent mitogenic activity susceptible to reinitiate DNA replication in quiescent rodent fibroblasts (CCL39, NRK-49F, NIH-3T3) but not in BHK-21 kidney cells. This activity appears to be closely related to platelet-derived growth factor (PDGF) based on 1) its cationic nature, heat and acid resistance, but sensitivity to reducing agents; 2) its apparent molecular weight (33 kDaltons) as estimated by Biogel filtration, once dissociated from binding proteins by mild acidic treatment; 3) its weak affinity for heparin; and 4) its ability to compete with 125I-PDGF for binding to human and rodent fibroblasts, and to be recognized by anti-PDGF antibodies. Although MeWo cells coexpress the PDGF-A and PDGF-B (c-sis) chain gene transcripts, the secreted product shows reactivity on CCL39 fibroblasts more compatible with the PDGF-BB than with the PDGF-AB isoform. MeWo cell lysates contain activities that bind moderately and strongly to heparin-Sepharose, being eluted with 1.0 and 2.0 M NaCl, respectively. The latter may correspond to basic fibroblast growth factor (basic FGF), consistent with the expression of basic FGF gene mRNAs. The former has not been fully characterized and is probably not the product of the acidic FGF gene. In addition, MeWo cells react positively with the FB2 AH7 antibody, thus indicating that they elaborate material similar to melanoma growth-stimulating activity (MGSA). MeWo cells proliferate in serum-free medium in a cell-density-dependent fashion, both in liquid and semisolid cultures. Their division is modestly enhanced by basic FGF and by human and porcine PDGF but not by the factors that they release. However, the absence of demonstrable 125I-PDGF binding sites on MeWo cells, in conjunction with their lack of sensitivity to suramin growth inhibition, suggests that the secreted PDGF does not act as an autocrine factor. Instead, the autonomous proliferation of MeWo melanoma cells may result from the concerted action of basic FGF and MGSA, which are mostly cell-associated.

Progressive relaxation of Go-arrest controls and altered responsiveness to insulin, EGF and thrombin in CCL39 lung fibroblasts over-expressing myc and ras oncogenes.

Factor-dependent hamster lung fibroblasts (CCL39) were transfected with plasmid vectors expressing normal Ha-ras, T24 Ha-ras, V-Ki-ras or myc oncogenes placed under the transcriptional control of potent viral or inducible (metallothionein-I) promoters. The rate at which clonal isolates proliferated in monolayer cultures in serum-free medium or in response to progression (insulin, EGF) and competence growth factors (alpha-thrombin) was found to vary according to the level of oncogene expression. Low levels of T24 ras gene did not abrogate Go-arrest controls but rendered CCL39 cells responsive to both insulin and EGF. Moderate levels (3- to 10-fold) of T24 and Ki-ras genes induced autonomous growth in serum-free medium and attenuated the cell responsiveness to all three factors. Growth of highest ras expressors was enhanced by low (less than 100 microM) concentrations of suramin, and was partially or not inhibited at higher concentrations. In contrast, EGF but not insulin, was able to recruit quiescent cells expressing moderate (less than or equal to 5-fold) myc levels. Higher levels conferred growth autonomy as well as hypersensitivity to insulin, EGF and thrombin. Suramin abolished the self-replication of such myc cells, thus suggesting an autocrine mechanism of proliferation. Hence, both myc and ras genes provided CCL39 cells with distinct growth competence functions which enabled these cells to respond overall more efficiently to functionally distinct classes of mitogens, or to sustain a completely autonomous replication, depending on the abundance of their respective products. Negative autoregulatory mechanisms may additionally be set into motion in this system when activated ras oncogenes are excessively expressed.

Pseudomonas aeruginosa sepsis presenting as peripheral subcutaneous nodules. Report of 2 cases.

Two patients developed disseminated subcutaneous nodules with febrile illness. In both cases, Pseudomonas aeruginosa was isolated from the lesions; blood cultures yielded the same organism in one case, and were negative in the other. The portal of entry was thought to be a jugular hemodalysis catheter in the first case and a necrotic zoster complicating lymphoma in the second case. Both patients' condition improved with antibiotic therapy and the Pseudomonas nodules resolved without surgical drainage.