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P Wolkenstein

Publications and source records attributed to P Wolkenstein.

At least 19 recordsLinked to original sources
PubMed2006

PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study.

The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis < or =40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common.

Basal Cell Nevus Syndrome↗
PubMed2005

Evaluation of skin viscoelasticity in type 1 neurofibromatosis patients.

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disease characterized by cutaneous benign tumors called neurofibromas. Surgery takes an important place in managing these skin disorders. However, skin distensibility and softness of NF1 patients quickly offset the surgical benefit. The aim of this study was to determine the rheological behavior of neurofibromas and compare it with healthy skin in an attempt to comprehend what leads to this phenomenon. Thirty patients were admitted to this study. A group of 24 healthy control subjects was also included. The skin elasticity was assessed by a noninvasive in vivo suction device (Cutometer) including 5 consecutive suctions. The assessments were performed on neurofibroma skin, the supposedly healthy skin around neurofibromas and the healthy skin of control subjects. The extensibility at the first and the fifth traction in NF1 patients (neurofibromas and the supposedly healthy skin around it) was significantly different compared to the healthy skin of control subjects. The viscoelastic parameters obtained from the neurofibromas were significantly different in comparison to those obtained from the supposedly healthy skin of NF1 patients and the healthy skin of control subjects. The rheological profiles of the neurofibromas and the apparent healthy skin of NF1 patients demonstrated a hyperextensibility behavior, but in neurofibromas, the skin was unable to return to its initial position at the end of the stretch.

Adolescent↗
PubMed2005

Association between benign and malignant peripheral nerve sheath tumors in NF1.

OBJECTIVE: People with neurofibromatosis type 1 (NF1) have a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). MPNSTs are often metastatic and are a frequent cause of death among people with NF1. Clinical evidence suggests that most MPNSTs in people with NF1 develop from preexisting plexiform neurofibromas. However, it is not known whether an individual's risk of developing an MPNST is associated with the burden of benign neurofibromas. The authors conducted a study to determine whether people with NF1 who have benign neurofibromas of various kinds are at greater risk of developing MPNSTs than patients with NF1 who lack these benign tumors. METHODS: Clinical information on 476 NF1 probands in the Henri Mondor Database was analyzed by logistic regression to examine associations between MPNSTs and internal plexiform, superficial plexiform, subcutaneous, and cutaneous neurofibromas. RESULTS: Individuals with subcutaneous neurofibromas were approximately three times more likely to have internal plexiform neurofibromas or MPNSTs than individuals without subcutaneous neurofibromas. Individuals with internal plexiform neurofibromas were 20 times more likely to have MPNSTs than individuals without internal plexiform neurofibromas. When this analysis was done with both subcutaneous and internal plexiform neurofibromas as explanatory variables, only the association of MPNSTs with internal plexiform neurofibromas remained significant. CONCLUSIONS: The observation that malignant peripheral nerve sheath tumors are strongly associated with internal plexiform neurofibromas suggests that patients with neurofibromatosis type 1 with these benign tumors warrant increased surveillance for malignancy.

Adolescent↗
PubMed2005

[Neurofibromatosis type 1 or Von Recklinghausen's disease].

OBJECTIVES: Neurofibromatosis 1(NF1) is one of the most common genetic diseases. NF1 is an autosomal dominant genetic disorder and half of affected individuals have NF1 as the result of a new gene NF1 mutation. The offspring of an affected individual have a 50% risk of inheriting the altered NF1 gene. The disease manifestations are extremely variable, even within a family. NF1 is characterized by multiple cafe au lait spots, axillary and inguinal freckling, multiple discrete dermal neurofibromas, and iris Lisch nodules. Learning disabilities are frequent. Less common but potentially more serious manifestations include plexiform neurofibromas, optic and other central nervous system gliomas, malignant peripheral nerve sheath tumors, vasculopathy, and osseous lesions. CURRENT KNOWLEDGES AND KEY POINTS: Since the original National Institutes of Health consensus Development Conference in 1987, there have been significant progress toward a more complete understanding of the molecular-bases for neurofibromatosis 1 and the routine follow-up for the care of the NF1 patients. The authors review the present data on the clinical and molecular aspects of the neurofibromatosis 1. FUTURE PROSPECTS AND PROJECTS: NF1 requires life-long management adapted to age and multidisciplinary structures are particularly well adapted to the diversity of the manifestations of this pathology. The French NF-France Network has been created in 2001 to federate the French multidisciplinary structures for neurofibromatosis and harmonize the follow-up of NF1 patients in France.

Genes, Neurofibromatosis 1↗
PubMed2005

[Neurofibromatoses and tuberous sclerosis].

Neurofibromatoses and tuberous sclerosis have specific genetic epidemiology, diagnostic criteria and management. These diseases are autosomal dominant disorders linked to mutations on tumour suppressor genes. Their management is mainly clinically oriented and aimed at managing potential complications.

Humans↗
PubMed2005

Symptoms associated with malignancy of peripheral nerve sheath tumours: a retrospective study of 69 patients with neurofibromatosis 1.

BACKGROUND: Neurofibromatosis 1 (NF1) is a common genetic disorder with variable clinical manifestations and an unpredictable course. Plexiform neurofibromas are common complications of NF1. Their malignant transformation is the main cause of mortality in adult patients with NF1. OBJECTIVES: To identify clinical factors associated with malignant transformation of plexiform neurofibromas. METHODS: Using the database of our neurofibromatosis clinic we included in a retrospective study all patients with NF1 having at least one peripheral nerve sheath tumour for which they underwent surgery or surgical biopsy. Predictive values for malignant transformation of three clinical symptoms, i.e. pain, enlargement of mass and neurological symptoms, were evaluated in association with histological parameters. RESULTS: Of 69 patients studied, 48 had at least one plexiform neurofibroma and 21 had a malignant peripheral nerve sheath tumour. Only enlargement of the tumour had high negative and positive predictive values for malignant transformation: 0.92 and 0.95, respectively. In multivariate analysis, tumour enlargement was independently associated with malignant transformation (odds ratio 167.8, 95% confidence interval 14.0-2012.1). CONCLUSIONS: From a practical point of view, pain, neurological deficit and enlargement of a pre-existing peripheral nerve sheath tumour in NF1 must lead to deep surgical biopsy to rule out malignant transformation.

Adolescent↗
PubMed2004

[Disulone].

For 60 years, dapsone has been used as a both antibacterial and anti-inflammatory agent. Dapsone (4,4'-diaminodiphenylsulfone, DDS) continues to be used successfully to treat a wide range of dermatologic disorders, notably those characterized by abnormal neutrophil and eosinophil polynuclear accumulation. A considerable number of other inflammatory as well as bullous dermatoses, of which dermatitis herpetiformis is the best known, have been shown to respond in varying degrees to dapsone, although the indication for the molecule has not been demonstrated in of them all. This article reviews current knowledge on the pharmacokinetics, mechanism of action and side effects of dapsone in dermatology. Despite the lack of controlled studies, the aim of this study is to specify and classify the pathological states in which disulone could be indicated.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Elevated risk for MPNST in NF1 microdeletion patients.

An NF1 microdeletion is the single most commonly reported mutation in individuals with neurofibromatosis type 1 (NF1). Individuals with an NF1 microdeletion have, as a group, more neurofibromas at a younger age than the group of all individuals with NF1. We report that NF1 microdeletion individuals additionally have a substantially higher lifetime risk for the development of malignant peripheral nerve sheath tumors than individuals with NF1 who do not have an NF1 microdeletion. This should be taken into account in the medical follow-up of individuals with an NF1 microdeletion.

Adolescent↗
PubMed2003

[Successful treatment of haemodialysis-related porphyria cutanea tarda with deferoxamine].

BACKGROUND: End-stage renal failure and long-term hemodialysis treatment promote porphyria cutanea tarda. Iron overload is often associated with this disease and is thought to play a role in its pathogenesis. We report a case of hemodialysis related-porphyria cutanea tarda improved by deferoxamine. CASE REPORT: A 45-year-old man, with end-stage renal failure and who had received hemodialysis treatment since 1993, presented a several months-history of blisters of the face and the dorsum of the hands. Laboratory analysis showed: hemoglobin 10 g/dl; a moderate hepatic cytolysis; ferritin 195 ng/l. HIV, HBV, HCV serologies were negative. Porphyries analyses showed a porphyria cutanea tarda pattern. The cutaneous histology was non specific; direct immunofluorescence was negative. The patient received deferoxamine (40 mg/kg intravenously every week for 6 weeks) which led to dramatic improvement of the symptoms. DISCUSSION: Several treatments are proposed in the management of dialysis-related porphyria cutanea tarda. This case confirms that deferoxamine can induce rapid and prolonged remission.

Deferoxamine↗
PubMed2003

[The French version of Skindex (Skindex-France). Adaptation and assessment of psychometric properties].

INTRODUCTION: The Skindex is an American tool designed to measure the impact of skin diseases on quality of life. The aim of our study was to adapt and validate this questionnaire in French in a population of patients with neurofibromatosis 1. MATERIAL AND METHODS: Translation and cultural adaptation: Translations were performed independently by two bilingual persons, then discussed. A preliminary version was obtained and confronted with 5 persons with low level of education and 6 patients with neurofibromatosis 1, before assessment in 24 neurofibromatosis 1 patients. The final version was named Skindex-France. Validation study: a test-retest study (1 month interval) was performed on 129 subjects with neurofibromatosis 1 to assess reliability and validity. RESULTS: Acceptability was good with a low rate of missing data (less than 5 p. 100). Ceiling and floor effects were less than 20 p. 100. The scores are sufficiently reliable (Cronbach alpha coefficient: emotions: 0.95, symptoms: 0.86, functioning: 0.94, and test-retest Spearman r: emotions: 0.92, symptoms: 0.84, functioning: 0.90). CONCLUSION: Skindex-France can be used to measure with precision the impact of skin diseases.

Adolescent↗
PubMed2003

[Cutaneous adverse drug reaction with pulmonary involvement].

INTRODUCTION: Cutaneous adverse drug reactions can be life-threatening: toxic necrolis and hypersensitivity syndrome or DRESS ("Drug Rash with Eosinophilia and Systemic Symptoms"). STATE OF THE ART: Pulmonary involvement is considered as a severity factor. During toxic epidermal necrolysis, pulmonary involvement is present in about 25% of cases; it corresponds to the detachment and the necrosis of bronchial epithelium. Specific bronchial involvement is of poor prognosis. During DRESS, pulmonary involvement is rare corresponding to an interstitial pneumonia with eosinophils. PERSPECTIVES: Progress in the knowledge of pathophysiology will help to target therapeutics. CONCLUSIONS: Early recognition of pulmonary complications must lead to adapt treatment and to improve prognosis.

Diagnosis, Differential↗
PubMed2002

Gliomas presenting after age 10 in individuals with neurofibromatosis type 1 (NF1).

Children with neurofibromatosis 1 (NF1) often develop low-grade gliomas, but brain tumors are infrequently encountered in adults with NF1. The authors present evidence from two clinical series, one including patients known to have NF1 and another focusing on adults with new onset brain tumors, that suggests an association between NF1 and symptomatic gliomas in older individuals. They also summarize the clinical data on 17 adolescents or adults with NF1 and symptomatic gliomas. The findings suggest that individuals with NF1 are at increased risk of developing gliomas throughout their lives.

Adolescent↗
PubMed2002

[Neurofibromatosis 1: recommendations for management].

Twenty experts, members of a French medical network devoted to neurofibromatosis 1 have elaborated recommendations for the management of the disease. Bibliography was obtained through a Medline of articles from 1966 to 1999 for the terms neurofibromatosis, NF1, neurofibroma and from textbooks. A consensual document was written taking into account extracted data. An annual careful clinical examination is recommended except in cases with complications. Screening investigations are not recommended due to the rarity of complications, generally symptomatic and easily detected during the clinical follow-up. The only controversial exception might be magnetic resonance imaging for early detection of optic pathway gliomas in young children. A co-ordinated follow-up in specialised multidisciplinary centres, providing patients with a rational management, is recommended.

Adolescent↗
PubMed2002

Clinical and genetic studies of Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant cancer syndrome characterised by benign skin tumours, renal tumours, and spontaneous pneumothorax. The gene has been mapped to chromosome 17p11.2 and recently identified, expressing a novel protein called folliculin. We report the clinical and genetic studies of four sporadic BHD cases and four families with a total of 23 affected subjects. Haplotype analysis of these families using BHD linked markers showed they did not share the same affected alleles, excluding common ancestry. Mutation analysis of the BHD gene identified two germline mutations on exon 11 (c.1733insC and c.1733delC) in three of four families as well as two of four sporadic cases. A novel somatic mutation, c.1732delTCinsAC, was detected in a BHD related chromophobe renal carcinoma. Our results confirmed the (C)8 tract in exon 11 as a mutational hot spot in BHD and should always be considered for future genetic testing. Our observation also indicated that the second hit (of Knudson's two hit theory) in some BHD related tumours is in the form of somatic mutation rather than LOH. In a large French family in which eight affected subjects carry the c.1733delC mutation, a phenocopy who has multiple episodes of spontaneous pneumothorax was identified. A total of five mutation carriers (aged between 37 to 66) did not have any evidence of BHD features, suggesting either reduced penetrance or late age of onset of the disease. In addition, six out of eight affected subjects who have positive germline mutation have confirmed neoplastic colonic polyps, indicating that colorectal neoplasia is an associated feature of BHD in some families. Our studies have observed several interesting genetic features in BHD: (1) the poly (C) tract in exon 11 as a mutational hot spot; (2) the existence of phenocopy; (3) reduced penetrance or late age of onset of disease; (4) association with colorectal neoplasia in some families; and (5) somatic mutation instead of LOH as the second hit in BHD tumours.

Adult↗
PubMed2002

[Blue-red macules and pseudoatrophic macules in neurofibromatosis 1].

INTRODUCTION: Blue-red macules are exception during neurofibromatosis 1. Between October 1988 and March 2000 in our cohort of patients, we systematically looked for these lesions. PATIENTS AND METHODS: Presence and number of blue-red macules were evaluated. Biopsies and photographs were proposed to patients. RESULTS: Forty-four patients out of 583 (39 y; range: 20-66 y) (7.5 p. 100; CI 95 p. 100: 5.5-9.8 p. 100) had blue-red macules mainly on the trunk. Histologically, blue-red macules corresponded to neurofibromatous tissue infiltrating capillary blood vessels and venules. CONCLUSION: Blue-red macules are a peculiar type of neurofibroma and can therefore be considered as a criterion for the diagnosis of neurofibromatosis 1.

Adult↗
PubMed2002

[Profuse scabies: kinetic curves of parasitologic cure with an association of benzyl benzoate and sulfiram].

BACKGROUND: In vitro exposure to benzyl benzoate (25 p. 100) kills Sarcoptes scabiei within three hours. The aim of our study was to determine in vivo elimination of Sarcopte scabiei with a benzyl benzoate-sulfiram association. METHODS: Medical charts of patients hospitalized for disseminated scabies from 1993 to 1999 were reviewed retrospectively. The diagnosis of scabies was confirmed by microscopic determination. Parasitological examinations were conducted every day or every two days until negative results. Patients were treated by successive applications of benzyl benzoate until parasitological cure. RESULTS: Twenty patients were included in the study. The median delay of parasitological cure was seven days. After 15 days, 95 p. 100 of patients were cured. Two cutaneous side-effects were reported. DISCUSSION: Despite immediate in vitro efficacy, benzyl benzoate action is delayed in vivo. The time of parasitological negativation after one application of benzyl benzoate is unknown. Therefore, it is not currently possible to determine whether our therapeutic regimen was excessive or not.

Aged↗