Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses.

Clusterin (Clu), an extracellular chaperone, exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains. In this study, we report that Clu also binds specifically to late apoptotic cells but not to live, early apoptotic, or necrotic cells. Histones, which accumulate on blebs during the apoptotic process, represent privileged Clu-binding motifs at the surface of late apoptotic cells. As a consequence, Clu potentiates, both in vitro and in vivo, the phagocytosis of late apoptotic cells by macrophages. Moreover, the increased phagocytosis of late apoptotic cells induced by Clu favors the presentation and cross-presentation of apoptotic cell-associated antigens. Finally, we observed that, in a model of apoptotic cell-induced autoimmunity, and relative to control mice, Clu(-/-) mice develop symptoms of autoimmunity, including the generation of anti-dsDNA antibodies, deposition of immunoglobulins and complement components within kidneys, and splenomegaly. These results identify Clu as a new molecule partner involved in apoptotic cell efferocytosis and suggest a protective role for Clu in inflammation and autoimmune diseases.

Surgical repair of labial defect.

The main cause of labial defect is carcinological, in 90% of cases involving the lower lip. Reconstruction for labial defect is a therapeutic challenge imposing two main requirements: to achieve good esthetic quality, and to conserve labial function. Steps of defect analysis is proposed. Very numerous techniques have been described that are not exhaustively explained in this surgical review. Thus, the authors suggest reliable, reproducible solutions that should enable the surgeon to deal with most of the labial defect situations encountered in practice, based on consensual indications. Node involvement and alternatives to surgery, such as X-ray therapy, also fall outside the field of the present article.

[Comparison and relevance of rheumatoid factors, antikeratin antibodies and anti-cyclic citrullinated peptides antibodies in rheumatoid arthritis]. / Comparaison et intérêt des dosages des facteurs rhumatoïdes, des anticorps anti-filaggrine (anti-kératine) et des anticorps anti-peptides cycliques citrullinés dans la polyarthrite rhumatoïde.

OBJECTIVES: to evaluate specificity and sensibility of the rheumatoid factors (RF), the anti-cyclic citrullinated peptide antibodies (CCP) and the anti-keratin antibodies (AKA) according to the rheumatoid arthritis (RA) diagnosis; pathology other than RA with at least one of these marker positive; the significance of the flocculent fluorescence of the antibodies AKA by indirect immunofluorescence (IIF). METHOD: two hundred forty height patients were studied: 121 RA, 89 inflammatory rheumatisms, 23 non inflammatory rheumatisms, and 15 non rheumatic affections. The RF was investigated by nephelometry, the anti-CCP by immunofluorometry and the AKA by IIF on rat oesophagus. RESULTS: specificity and sensibility were respectively in a retrospective manner: 68% and 83% for the RF, 95% and 76% for the anti- CCP, 83% and 40% for the AKA during RA with evolution of less than one year. The rates of agreements were: RF versus CCP: 81%, RF versus AKA: 57%, CCP versus AKA: 73%. Twelve patients with pathologies different from RA have positive anti-CCP or AKA. Thirty three of the patients with anti-CCP level superior to 130 U/mL have flocculent AKA versus only 5% when the anti-CCP are lower than 130 U/mL. CONCLUSION: the RF and the anti-CCP are complementary in RA. Autoimmune and neoplasic pathologies are sometimes responsible for the positivity of the anti-CCP and the AKA. The flocculent aspect of AKA in IIF may be associated with raised concentrations of anti-CCP.

Antineutrophil cytoplasmic autoantibodies: how should the biologist manage them?

Antineutrophil cytoplasmic antibodies (ANCA) are directed against enzymes found in the granules of the polymorphonuclear (PMN) leukocytes. They are detected by indirect immunofluorescence microscopy assays on human ethanol fixed neutrophils. Three different fluorescence patterns can be distinguished: a cytoplasmic pattern (cANCA), a perinuclear pattern (pANCA), and an atypical pattern (aANCA). The use of other fixatives, e.g., formalin and methanol, allows differentiation between the pANCA and the antinuclear antibodies. ANCA specificity is determined by solid phase assays (ELISA, immunodot, and multiplex assay). ANCA with high titres and defined specificities (antiproteinase 3 [PR 3] or antimyeloperoxidase [MPO]) are proven to be good serological markers of active primary systemic vasculitis: c/PR 3-ANCA for Wegener's granulomatosis and p/MPO-ANCA for microscopic polyangiitis. The former have higher sensitivity and specificity for Wegener's granulomatosis than the latter for microscopic polyangiitis. ANCA with low titres and unknown specificity have been detected in a wide range of inflammatory and infectious diseases leading to a critical reappraisal of the diagnostic significance of ANCA testing. Physicians must keep in mind the possible occurrence of infectious diseases like subacute endocarditis that could be dramatically worsened by irrelevant immunosuppressive therapy. ANCA findings in certain manifestations, such as the pulmonary-renal syndrome in which massive pulmonary hemorrhage can quickly be life-threatening, warrant ANCA testing as an emergency test for patient care.

Reference frames in reading: evidence from visually and memory-guided saccades.

In order to examine the frames of reference used for the planning of inter- and intra-word saccades, subjects were required to execute a two-saccade sequence toward one or two words. The first saccade was visually guided while the second saccade was visually or memory-guided. Results demonstrate that readers hold an internal representation of the target word in at least two different reference frames that are specific to the action to be performed: to aim for a new target word or to read it over with a second fixation. When a word is selected as a target for the next saccade, the spatial location of the second word is stored in memory. Then, the second saccade is updated with respect to the current eye position in the first word in order to aim a functional target location in the second word that is the word's center. When the second saccade is directed within the fixated word, the saccadic system uses the intrinsic features of the word to code a fixed-motor vector relative to the word's length. Our present results demonstrate that readers hold an internal representation of the saccade target in different reference frames specific to the action performed on the word.

The planning of refixation saccades in reading.

The planning of the refixation saccade, i.e. the second saccade on 9- and 11-letter-strings, was assessed in two reading experiments that examined the influence of a length change at different times during the first fixation on a letter string. The results showed that the saccadic system was able to modify the first motor program if the new length information was available 150-190 ms before the execution of the refixation saccade. Moreover, the amplitude of the refixation saccade was found to be planned as a constant movement relative to the length of the item, regardless of the position of the initial fixation on the item. Finally, the refixation saccade seems to be preprogrammed before the primary saccade, depending on the length integrated at that time. Overall, these results suggest that the refixation saccade is programmed on the basis of the intrinsic properties of the item, such as its length.

Short therapy with amoxicillin-clavulanate and corticosteroids in acute sinusitis: results of a multicentre study in adults.

Evolution of bacterial resistance shortens antibiotic treatment in ENT infections. The efficacy and tolerance of amoxicillin-clavulanate (ACA), with and without associated short steroid therapy, was evaluated in acute sinusitis of adults at a dosage of 1.5 g/d for 5 d vs. 10 d. This multicentre, randomized, double-blind, placebo-controlled study included 433 patients, 417 of whom were suitable for intent-to-treat (ITT) analysis. The therapeutic success rate in the ITT population, assessed according to strict clinical and radiological criteria, was respectively, 80% and 85% in the 5-d and 10-d treatment groups. Due to the statistical risks that were evidenced, the 2 durations of treatment could not be considered equivalent. The analysis of medical history shows that some risk factors (recurrence of sinusitis, previous surgical sinus drainage) seem to promote therapeutic failure and that 5-d treatment is inappropriate in these patients. The persistence of therapeutic success on day 30 was not influenced by the initial duration of treatment. The efficacy and good tolerance of ACA in acute sinusitis in adults were confirmed. Further studies will be needed to define the indications of short treatments better, which seem to be indicated in the absence of specific risk factors.

Orthographic codes are used in integrating information from the parafovea by the saccadic computation system.

Two experiments that examined the characteristics of information extracted from a parafoveal letter string by the saccadic system are reported. In Experiment 1, we observed the effect of the orthographic legality of the initial letter sequence on landing positions. The deviation of landing positions towards an orthographically illegal letter sequence was shown to occur in saccades when subjects were instructed to read a nonsense letter string. Moreover, it was shown that the initial placement of the eyes is influenced by the frequency of occurrence of the letter sequence and not by the frequency of the letters that formed this sequence. Experiment 2 followed up on the implication that readers use orthographic information only from the initial letters of the parafoveal string. We concluded that the saccadic computation system integrates orthographic information from the two initial letters.

Latency dependence of word-initial letter integration by the saccadic system.

Two experiments are reported in which saccadic eye movements were examined when the eyes moved to words in which the properties of the word-initial letters differed. It was found that the effect of saccade latency on landing position depended on the properties of the word-initial letters. Under short saccade latencies, landing positions deviated toward the word beginning in the presence of orthographically irregular/informative beginning (OI/IB) letters. This result is interpreted as an influence of the orthographic encoding process that has detected an unusual letter grouping. With longer saccade latencies, an increase of the saccade size was observed for OI/IB words, whereas orthographically regular/uninformative beginning words did not show the effect. It is suggested that this may be a consequence of the dynamics of parafoveal word information processing.

Final results of a randomized trial comparing chemotherapy plus radiotherapy with chemotherapy plus surgery plus radiotherapy in locally advanced resectable hypopharyngeal carcinomas.

After neoadjuvant chemotherapy, a routine conservative approach followed by salvage surgery was evaluated in terms of local control and survival in cases of advanced potentially resectable hypopharyngeal carcinoma. Between 1985 and 1989, 92 patients with T3 or T4-NO,N3 operable squamous cell hypopharyngeal carcinomas received three courses of neoadjuvant chemotherapy every 2 weeks involving a combination of cisplatin, 100 mg/m2, on day 1 and fluorouracil, 1 g/m2, on days 2 to 5, followed by total laryngopharyngectomy plus postoperative radiotherapy in 47 patients (arm A) or radiotherapy alone in 45 patients (arm B). Randomization was always performed prior to chemotherapy. The response rates of tumor and node to chemotherapy were, respectively, 67% in arm A versus 79% in arm B (P > 0.05) and 54% in arm A versus 73% in arm B (P > 0.05). Grade III or IV toxicity was similar, affecting 15% of patients and 7% of cycles in arm A versus 16% of patients and 6% of cycles in arm B. After a mean follow-up of 92 months, survival was statistically better (P = 0.04) in arm A (5-year overall survival, 37%; median survival, 40 months) than in arm B (19% and 20 months) because of a better local control rate (63% versus 39%; P < 0.01). Better results were obtained for mutilant surgery in terms of local control and overall survival, regardless of response to neoadjuvant chemotherapy.

The 'center of gravity' of words: evidence for an effect of the word-initial letters.

When the eye saccades to eccentric word targets, it tends to land in a position which can be described as the center of gravity of the configuration. By manipulating the relative intensity of the word-initial and -ending letters, it was shown that the 'global effect' of luminance distribution within words is strongly attenuated when the word-initial letters are informative and orthographically irregular. Results show that the orthographic structure of the word-initial letters exerts an influence on the saccadic computation that may cancel the luminance distribution effect.

[Restoration of the mandible after trans-mandibular approach of invasive tumors of the oropharynx (43 cases)]. / La réparation de la mandibule après abord transmandibulaire des tumeurs étendues de l'oropharynx (43 cas).

Preservation of the mandible is often possible in surgery of invasive malignant tumors of the oropharynx. From 1983 to 1993, we operated 158 T3 of the oropharynx: 73% with mandibulectomy and 27% with osteotomy (43 cases). Now, the osteotomy of the mandible is performed in more than 90% of the patients. The osteosynthesis needs two titanium plates; the pharyngoplasty is made with a pectoralis major myocutaneous flap. Followup: 36 cases of 43 gave satisfactory results. The osteotomy complication rate was 5 (12%): 5 osteitis (2 after radiotherapy).

[Two-stage excision of extensive cutaneous carcinoma of the face. A retrospective study of 80 patients]. / Exerese en deux temps des carcinomes cutanes etendus de la face. Etude retrospective de 80 malades.

INTRODUCTION: Delayed reconstruction (two-step surgery) comprised of tumor resection and repair three or four days later, after paraffin tissue fixation and histopathological examination, is one of the techniques used for complete excision of spreading cutaneous carcinomas. PATIENTS AND METHODS: In order to evaluate the efficacy and long term prognosis of delayed reconstruction surgery, we carried out a retrospective study of 80 patients treated by this method and (Kaplan- Meier) for correlation with the local recurrence rate: sex, age, anatomic site, histologic type and existence of previous therapy. Long term results have been estimated. Among the 80 patients studied, 76 patients have been followed. The sex-ratio was 0.48. Fifty-two percent of the population was more than seventy years old. Fifty-five percent of the tumors were situated on the nose. In 32,5 p. 100 of the cases, a prior therapy (surgery, electrodessication or radiation therapy) has been carried out. Histological analysis showed 87 p. 100 basal cell carcinomas (of which 26 p. 100 of morpheaform basal cell carcinomas) and 13 p. 100 squamous cell carcinomas. RESULTS: After the first operative step, there was total excision in 69 p. 100 of thecases. In the remaining cases, a second excision was performed with a margin of normal tissue. Recurrences were observed (some precocious recurrences and some late recurrences) in 18.4 p. 100 of the cases. No risk factor correlated significantly with the recurrence rate. However, analysis of the survival graph suggests that the squamous cell carcinomas recurred more often than the basal cell carcinomas. CONCLUSIONS: Although extemporaneous examinations (Mohs' technique) remains the gold standard technique in the management of spreading cutaneous carcinomas of the face, the delayed reconstruction (two-step surgery) is a credible alternative when compared to the recurrence rates reported in the literature with the other techniques (electrodessication, radiation therapy or cryosurgery).

Controlled prospective study of oral ciprofloxacin versus amoxycillin/clavulanic acid in chronic suppurative otitis media in adults.

The efficacy and tolerability of ciprofloxacin (500 mg twice daily) was compared with that of amoxycillin/clavulanic acid (500 mg three times daily) in 76 patients with acute exacerbations of chronic non-cholesteatomatous suppurative otitis media enrolled in this open randomized multicentre trial. A total of 40 ciprofloxacin-treated patients and 35 amoxycillin/clavulanic acid-treated patients were evaluable for clinical efficacy following the 9-day treatment period. Pseudomonas aeruginosa was the main pathogen isolated prior to treatment. At the end of treatment, otorrhoea had disappeared in 57.5% of the ciprofloxacin group and 37.1% of the amoxycillin/clavulanic acid group (p = 0.04). Bacterial eradication rate was also significantly greater with ciprofloxacin (69.7%) than with amoxycillin/clavulanic acid (27.3%). Both treatments were well tolerated. Ciprofloxacin appears to be an effective treatment of chronic otitis media, and superior to amoxycillin/clavulanic acid.

A double-blind comparison of ciprofloxacin and amoxycillin/clavulanic acid in the treatment of chronic sinusitis.

A total of 251 adults with chronic sinusitis were enrolled into this prospective multicentre, double-blind, double-placebo comparison of ciprofloxacin (500 mg twice daily) with amoxycillin/clavulanic acid (500 mg three times daily). The diagnosis of chronic sinusitis (persistence of clinical symptoms for at least 3 months) was confirmed by computerized tomography scan and/or sinusoscopy prior to therapy. Patients at inclusion had purulent or muco-purulent rhinorrhoea. Staphylococcus aureus (n = 45), Haemophilus influenzae (n = 35), Streptococcus pneumoniae (n = 32) and enterobacteriaceae (n = 31) were isolated from pre-treatment aspirates of the middle meatus. Treatment lasted 9 days, at the end of which nasal discharge disappeared in 71/118 (60.2%) patients of the ciprofloxacin group and 69/123 (56.1%) of those in the amoxycillin/clavulanic acid group. The clinical cure and bacteriological eradication rates were 58.6% versus 51.2% and 88.9% versus 90.5% for ciprofloxacin and amoxycillin/clavulanic acid, respectively. These differences were not significant, however, amongst patients who had a positive initial culture and who were evaluated 40 days after treatment. Ciprofloxacin recipients had a significantly higher cure rate than those treated with amoxycillin/clavulanic acid (83.3% vs. 67.6%, p = 0.043). Clinical tolerance was significantly better with ciprofloxacin (p = 0.012), essentially due to a large number of gastro-intestinal related side-effects in the amoxycillin/clavulanic acid group (n = 35). Ciprofloxacin proved to be at least as effective as amoxycillin/clavulanic acid. The superior safety profile, a twice daily dosage regimen, suggests that ciprofloxacin may be a useful therapeutic alternative for the treatment of chronic sinusitis.

[Perilymph fistula: diagnosis by detection of perilymph in the middle ear by beta-2 transferrin immunofixation]. / Fistules périlymphatiques: diagnostic par la détection de la périlymphe dans l'oreille moyenne par immunofixation de la beta 2 transferrine.

beta 2-transferrin is a specific protein found in the cerebrospinal fluid and in the perilymph. Detecting beta 2-transferrin in the middle ear is of great interest when a fistula of the perilymph is suspected. This protein can be detected on microsamples with an immunofixation technique. We searched for beta 2-transferrin in pure perilymph, cerebrospinal fluid and serum in 8 patients operated by translabyrinthine approach for acoustic tumor removal. Search for beta 2-transferrin was performed in liquid from the inner ear in 3 labyrinthectomies. Samples were taken on collagen sponges or with micro syringes. beta 2-transferrin was detected in the perilymph of patients operated for neurinoma and in 2 of the 3 labyrinthectomies. This protein was found in only one of the patients for which the diagnosis of perilymphatic fistula had been retained. Detection of beta 2-transferrin in the middle ear can be proposed as a specific diagnostic test for perilymphatic fistula when the clinical situation does not suggest a fistula involving cerebrospinal fluid.