Biomedical subjects
J M Bonnetblanc
Publications and source records attributed to J M Bonnetblanc.
[Tolerance and feasibility of adjuvant treatment of stage II malignant melanoma with high-dose interferon-alpha].
BACKGROUND: The use of high-dose interferon alpha as adjuvant therapy has been shown for the first time to improve recurrence-free and overall survival in stage II malignant melanoma. The aim of our work was to evaluate the toxicity of this therapeutic scheme during a 1-year period in 13 patients with malignant melanoma. PATIENTS AND METHODS: Thirteen patients, mean age 56 years, with stage II melanoma were included. Interferon alpha was administered at the dose of 20 MU per m2 body surface area five days per week for four weeks during the induction phase and at the dose of 10 MU subcutaneously three times a week for 48 weeks in the maintenance phase. Patients underwent clinical assessment daily and had blood tests twice a week during the induction phase. Weekly blood tests and monthly examinations were then performed during the maintenance phase. Clinical and biological toxicity was evaluated in accordance with the WHO scores. Grade 3 toxicity led to a 30 p. 100 dose reduction and treatment was interrupted in case of grade 4 toxicity. RESULTS: A flu-like syndrome (grade 1-2) and digestive disorders, nausea, anorexia related to dysgeusia or dry mouth were observed in most of the patients during the induction phase and persisted in 30% of the patients during the maintenance phase. Six patients developed a state of depression (grade 2-3) which persisted during the maintenance phase, inciting us to prescribe an antidepressor regimen for all our patients. One patient developed major reversible alopecia at dose reduction. Nine patients had grade 1 or grade 2 neutropenia and four had grade 3 neutropenia. Seven patients developed grade 1-2 thrombocytopenia, six had elevated transaminase levels (grade 1-2) and two moderately elevated CPK. CONCLUSION: At the end of the induction phase of interferon alpha therapy in 13 patients with malignant melanoma, 8/13 had received 100 p. 100 of the theoretical dose and 11/13 had received 80 p. 100. At the end of the treatment protocol, 5/10 patients had received 100 p. 100 of the theoretical dose and 8/10 more than 80 p. 100. The proposed protocol appears to be feasible without major risk. Rigorous clinical and biological surveillance is mandatory.
[Penile lichen sclerosus: follow-up study].
INTRODUCTION: The aim of this work was to study the long-term course of patients with penile lichen sclerosus and atrophicus. PATIENTS AND METHODS: We reviewed the files of 16 patients followed at our university center from 1982 to 1997 for pathologically proven penile lichen sclerosus and atrophicus. Age at disease onset, duration of the disease course, presence of a triggering factor, initial localization, signs and symptoms, treatment given and its efficacy were recorded. RESULTS: Mean age at diagnosis was 52 years. Inaugural prepuce localizations were observed in 6 cases, involving the distal part of the penis and the glan in 3 cases. Concomitant involvement of the glan and the balanopreputial groove were seen in 6 cases. The localization was limited to the glan in one case. Six patients underwent posthectomy and one had dorsal plasty of the prepuce. The 9 other patients were treated medically with topical corticosteroids and/or androgens. One patient had died prior to evaluation. Among the 9 patients given medical treatment, lichen sclerosus persisted in 7, one developed a squamous cell carcinoma of the penis and one was cured. Among the 6 cases of surgical treatment, 5 were cured and 1 had persistent lesions. Considering the initial localization, long-term course showed that 7 of the 8 patients with a prepuce localization (alone or in association with glan involvement) were cured while the 7 patients with a lesion of the balanopreputial groove (alone or in association with glan involvement) or a lesion of the glan alone still had lichen sclerosus and atrophicus. The non parametric Fischer test showed that the chances of cure were better for preputial localizations than for balanopreputial localizations (p = 0.001) and that surgical treatment was more effective than medical treatment. DISCUSSION: This study of a small number of patients highlighted two points: prepuce localizations of lichen sclerosus and atrophicus cure better than balanopreputial localizations, and that medical treatment is partially effective in balanopreputial localizations. One patient developed squamous cell carcinoma of the penis. As the level of the cancer risk remains unknown, it would be important to provide the most effective treatment in all cases of penis lichen sclerosus and atrophicus.
[Nicolau's livedoid dermatitis].
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The naevoid basal-cell carcinoma syndrome (Gorlin syndrome) is a chromosomal instability syndrome.
The Gorlin syndrome, or naevoid basal-cell carcinoma syndrome (NBCS) is an autosomal dominant cancer prone disease (at risk of multiple basal cell carcinomas, and other malignant or benign proliferations). We have previously reported data from peripheral blood lymphocytes of patients with this condition, showing a significant level of spontaneous chromatid and chromosome rearrangements and an overall lengthening of the cell cycle. In this paper, we confirm this disease to be a chromosome instability syndrome from studies on fibroblasts of 5 patients. Spontaneous chromosomal rearrangements, an increased frequency of sister chromatid exchanges and a slowing of the cell cycle were found, compared to age-matched control material. There was also an increased sensitivity to aberration production by mechlorethamine in patient fibroblasts. The chromosome instability we found was not restricted to a given cell lineage, but appears to be part of the general condition of this syndrome. The recently discovered gene responsible for Gorlin syndrome, PTC (or PTCH), encodes a transmembrane protein with yet poorly known functions. However, the demonstration of Gorlin syndrome as a chromosome instability syndrome suggests that this protein has a role in DNA maintenance, repair and/or replication.
Bullous pemphigoid induced by bumetanide.
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Pyoderma gangrenosum complicating Cogan's syndrome.
Cogan's syndrome is a rare clinical entity defined by the association of a nonsyphilitic interstitial keratitis and vestibuloauditory dysfunction, typically Menière's disease-like; the condition has been reported in association with a variety of cutaneous diseases. We now report a case of pyoderma gangrenosum complicating Cogan's syndrome in a 57-year-old woman, which then healed dramatically, as more interestingly did the associated uveitis with minocycline therapy.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.
[Drug hypersensitivity syndrome: research of etiology].
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[Drug-induced acrosyndromes].
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[Case for diagnosis. Leg ulcer secondary to drepanocytosis].
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[Giant buccal aphthosis caused by nicorandil].
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Bullous pemphigoid and cicatricial pemphigoid autoantibodies react with ultrastructurally separable epitopes on the BP180 ectodomain: evidence that BP180 spans the lamina lucida.
The BP180 antigen is a hemidesmosomal glycoprotein that is recognized by autoantibodies associated with three autoimmune disorders, bullous pemphigoid (BP), herpes gestationis (HG), and cicatricial pemphigoid (CP). BP and HG sera have been shown to recognize a common extracellular site located near the membrane-spanning domain of this protein, whereas CP sera react predominantly with a distinct site near the C terminus. In the current study, the main immunogenic sites on the BP180 ectodomain were ultrastructurally localized using six BP sera, four CP sera, and two rabbit antisera. The immunolocalization pattern of BP sera was largely restricted to the upper lamina lucida region immediately subjacent to the epidermal hemidesmosome and closely resembled that of a rabbit antiserum directed against the NC16A (membrane-proximal) domain of BP180. CP sera, on the other hand, exhibited a lower lamina lucida/lamina densa labeling pattern that was strikingly similar to that of rabbit antibodies to the BP180 C-terminal region. Finally, antibodies to the BP180 C-terminal region co-localized with an anti-laminin-5 antibody in the anchoring filament zone. These findings strongly suggest that the BP180 extracellular domain exists in an extended conformation, with the C terminus of this protein projecting into the lamina densa. These data support the hypothesis that BP180 contributes to the structure and function of the anchoring filaments. Differences in the ultrastructural mapping of BP and CP autoantibodies appear to correlate with epitope mapping data, which, together, may help to explain the clinical heterogeneity observed in this group of bullous disorders.
Bullous lichen sclerosus with chronic hepatitis C virus infection.
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Postoperative interstitial radiotherapy of keloids by iridium 192: a retrospective study of 46 treated scars.
BACKGROUND: Keloids are clinically vexacious scars characterized by a high recurrence rate after excision alone (50-100%). Many adjuvant techniques have been used with more or less convincing results. OBJECTIVE: The aim of this study is to show the efficiency of keloidectomy and postoperative interstitial radiotherapy by an iridium 192 wire. METHODS: During a 14-year period, 39 patients with keloids (46 keloids) were treated by this regimen. Seven patients had been previously treated by intralesional corticosteroids, surgery alone or postoperative interstitial radiotherapy, without improvement. A dose of 12 Gy (7 keloids) to 15 Gy (22 keloids) was delivered at a point 2.5 mm from the axis of the wire. For 17 keloids the dose schedule was 15 Gy at a point 5 mm to the wire. The median follow-up was 7 months. RESULTS: The overall success rate is close to 63%. A recurrence occurred in 14 cases without relation to the method used, the age or the localization of the lesions. There were no side effects observed. CONCLUSIONS: Postoperative interstitial radiotherapy represents an effective, unconstraining and safe treatment for keloids if the contraindications are respected.
Anti-BP180 autoantibodies as a marker of poor prognosis in bullous pemphigoid: a cohort analysis of 94 elderly patients.
The prognosis of bullous pemphigoid (BP), a disorder which usually affects elderly patients, is not well established and conflicting data have been reported about the mortality rate of the disease. Our objective in this study was to assess the clinical and immunological factors determining survival in a prospective series of 94 patients with BP. A cohort of 94 consecutive patients with BP (mean age +/- SD: 81 +/- 4 years) was studied over an 8-year period (1987-94) in one department and patients followed up for at least 1 year. The diagnosis of BP was made on clinical criteria (using a standardized questionnaire), direct immunofluorescence (IF) findings (i.e. linear deposits of IgG and/or C3 along the basement membrane zone) and confirmed by direct immunoelectron microscopy and/or Western immunoblotting. Our analysis (median duration of follow-up: 5 years) showed that 37% of BP patients were dead within a year of starting treatment. The clinical or immunological factors which may influence the prognosis of BP were studied according to the criterion of death or survival by the end of the first year of treatment. None of the following factors was found to be significantly linked to the prognosis in BP: age, sex, extent of skin lesions at presentation, presence of mucosal lesions, blood eosinophilia, or the presence of circulating basement membrane zone autoantibodies by indirect IF. An impaired general condition and a history of coronary artery disease indicated a bad prognosis. The presence of circulating autoantibodies against BP180 autoantigen but not autoantibodies against BP230, as detected by immunoblotting on epidermal extracts, was found to be significantly more frequent (60% vs. 25%) in BP patients who died within the first year of treatment (P < 0.01). We conclude that the presence of circulating autoantibodies against BP180 represents the first intrinsic prognostic factor that has been demonstrated in BP. This result supports the growing body of evidence for the pathophysiological importance of the anti-BP180 autoantibodies.
[Pemphigoid vegetans. An immunoelectron microscopic study].
INTRODUCTION: Pemphigoid vegetans is a rare disease. It has a clinical resemblance to pemphigus vegetans, but there are histological and immunopathological features of bullous pemphigoid. CASE REPORT: We describe a case in a 57-year-old-man who had developed intertriginous vegetating plaques. Histologic examination of a skin biopsy specimen and direct immunofluorescence microscopy of a biopsy specimen were those of bullous pemphigoid. Immunoblot studies and indirect immunofluorescences of salt-split skin were negative. Direct immunoelectron microscopy was consistent with bullous pemphigoïd. DISCUSSION: Only five cases have been reported. We describe the first case including direct immunomicroscopic findings which suggest that pemphigoid vegetans is a subtype of bullous pemphigoid. The other interest was a remarkable improvement with tetracyclines.
[I RPHUSE, I RMR, I treat].
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