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Biomedical subjects

F Waridel

Publications and source records attributed to F Waridel.

9 recordsLinked to original sources

[Indications for tonsillectomy in 2005].

Tonsillectomy is one of the most frequent ENT operations but yet a very disputed one. The majority of children and adults are treated for recurrent angina, which is validated by several clinical trials. For an adult a peritonsillar abscess is best treated by immediate tonsillectomy. Incision and drainage is a validated method as well, as long as there is no indication to a delayed tonsillectomy. The tonsillectomy alone is not a validated treatment for adult upper airway obstruction. On the other hand it is a recommended procedure for children upper airway obstruction. Partial tonsillectomy (tonsillotomy) is also a validated procedure for this indication. Finally the peritonsillar abscess in a child should first be treated by one or two days of intravenous antibiotics.

Abscess↗

Fate and functions of human adult lymphoid cells in immunodeficient mice.

Laboratory models enabling to study in vivo human leukocyte functions have been developed. Most of the models consist of human immunocytes transferred to mice homozygous for the scid mutation. Mice with additional immunodeficient-prone genetic background or with immunodeficiency-induced conditioning have also been used. Human grafts mainly consisted of human immune cells in suspension injected intraperitoneally, or in pieces of human organs containing immunocytes implanted subcutaneously. Cells in suspension could be easily manipulated in vitro before transfer to the animal, but disseminated within the mouse body. In opposition, human cells mostly remained within implantation areas of animals given human organ pieces. This favorizes cell interactions and helps for cell recovery after their in vivo passage. Moreover, the diversity of antibodies in animals transplanted with human lymphoid organ pieces appeared broader than that of mice transferred with lymphocytes in suspension. Spontaneous recall antibody and autoantibody productions have been generally observed in animals transferred with cells from donors with such antibodies. In vivo boosting of recall antibody by antigen has been most successful, but such a manipulation inconstantly boosted autoantibodies. Primary human T and B cell responses were difficult to obtain in xenochimeric animals, and success has been generally obtained by optimizing human immune response parameters, such as antigen presentation.

Animals↗

[Value of fine needle aspiration biopsy in diagnosis of cervical masses].

Fine needle aspiration is a widely used diagnostic tool. Its use for the evaluation of head and neck masses remains somewhat controversial. This retrospective study analyses all patients presenting with neck masses investigated by fine needle aspiration in our institution from January 1997 to December 1998. 372 fine needle aspirations were performed. Cytological diagnosis was possible in 91%. Sensitivity was found to be 100%, specificity 99% and accuracy 99.7%. When including indeterminants in the false-negatives, overall sensitivity is 73%, overall specificity 100% and overall accuracy 90%. There were no complications, and in particular no suprainfection and no tumoural spread at the puncture site. We conclude that fine needle aspiration is a sensitive and specific modality which is very helpful in the diagnostic work-up of a neck mass.

Biopsy, Needle↗

Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract.

Field cancerisation of the aerodigestive tract is caused by chronic exposure to alcohol and tobacco, but the nature of the genetic alterations preceding overt malignancy is unknown. To identify potential field changes we have used a functional assay which tests the transcriptional competence of human p53 expressed in yeast. To increase the sensitivity and reliability of the technique for samples containing under 20% mutant p53, the 5' and 3'-ends of the p53 cDNA were examined separately. With this split form of the assay the tissue p53 mRNA acts as its own control for RNA quality. Mutations were detected in 87% (46/53) of tumours, reflecting the high sensitivity of the technique. Multiple biopsies of histologically normal tissue from the upper aero-digestive tract were tested and clonal p53 mutations were identified in 76% (38/50) of biopsies from patients presenting with multiple tumours compared with 32% (38/117) of biopsies from patients presenting with single tumours (P<0.000001). All patients (16/16) presenting with multiple tumours had at least one positive biopsy, compared with only 53% (19/36) of patients presenting with single tumours (P <0.001). This defines expansion of multiple clones of mutant p53-containing cells as an important biological mechanism of field cancerisation, and provides a means to identify patients likely to benefit from intensive screening for the development of new head and neck tumours.

Adult↗

Evaluation of the bone resistance of the sphenoid and ethmoid sinuses.

Functional endoscopic sinus surgery can be associated with iatrogenic complications. Some anatomical structures have been identified this clinically as specific danger sites. The aim of this study was to confirm and to compare these clinical data with measurements of the bone resistance of the sphenoid and ethmoid walls and to point out regions that have increased bony fragility. Critical dynamometric evaluation of the resistance to breakage of these bony structures was made on 21 anatomic specimens. This study allowed the authors to localization of surgical complications, to demonstrate that other regions renowned for their fragility can be relatively robust, and to point out that robust sites can be dangerously fragile as a result of individual morphological variations. Results from this study provide a supplement to the guidelines for novice surgeons to use in identifying dangerous areas.

Endoscopy↗

Reappraisal of p53 mutations in human malignant astrocytic neoplasms by p53 functional assay: comparison with conventional structural analyses.

We previously reported clonal expansion of p53 mutations in malignant astrocytic tumors detected with a yeast p53 functional assay that measures mutant p53 alleles quantitatively and loss of p53 transcriptional competence qualitatively (Tada et al., Int J Cancer 67:447-450, 1996). This method selectively detects inactivating mutations and is relatively insensitive to contamination of tumor samples with normal tissue. To determine whether the mutation frequency and spectrum detected in this way differ from those seen with conventional techniques, 54 malignant astrocytomas were tested with the yeast assay, and the abnormalities detected were characterized by DNA sequencing. Inactivating p53 mutations were found in 67% of anaplastic astrocytomas and 41% of glioblastomas. Overall, mutations were found in 48% of tumors, compared with only 29% in previous studies (P < 0.005), a difference that probably reflects the greater sensitivity of the yeast assay than of conventional techniques. The frequency of mutations in anaplastic astrocytomas (in our study plus published studies) was significantly higher than in glioblastomas (39% vs 29%; P < 0.05). This suggests that acquisition of p53 mutations is not rate limiting for progression to glioblastoma and that many glioblastomas develop by p53-independent pathways. Sequencing of mutant p53 cDNAs rescued from yeast showed that the mutation spectrum for functionally inactive mutants was nearly identical to the spectra from previous studies on structural mutants, indicating that transcriptional activity is the critical biological target of p53 mutation in malignant astrocytomas.

Adult↗

The human tumour suppressor gene p53 is alternatively spliced in normal cells.

Alternative splicing affecting the p53 carboxy-terminus has previously been described in mouse but not in normal human cells. We report here the detection in normal human lymphocytes of an alternatively spliced form of human p53 mRNA containing an additional 133 bp exon derived from intron 9. This splice variant encodes a truncated protein of 341 amino-acids including 10 new amino-acids derived from the novel exon. The truncated protein, which lacks part of the p53 tetramerization domain, fails to bind DNA in vitro and has a transcriptional defect in vivo in both yeast and mammalian cells. Quantitative RT-PCR experiments suggest that the alternatively spliced form is only present in significant amounts in quiescent cells. Considering the numerous functions ascribed to the carboxy-terminus of the p53 protein, this splice variant may have important implications for the biological role of p53 in normal cells.

Alternative Splicing↗