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P Wolkenstein

Publications and source records attributed to P Wolkenstein.

At least 37 records · Page 2Linked to original sources
PubMed2001

Serotonin transporter gene polymorphism and psychiatric disorders in NF1 patients.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disease characterized by a broad clinical expression. Comorbid affective disorders, anxiety disorders, and suicide are frequently observed during NF1. The promoter marker (5-HTTLPR) of the serotonin transporter gene (5-HTT) has been shown to be associated with major affective disorders, anxiety-related trait, and more recently with suicidal behavior. This gene is adjacent to the NF1 gene, raising the question of the implication of the 5-HTT gene in the psychiatric comorbidity during NF1. Eighty-eight patients with NF1 and 184 screened controls were typed for the 5-HTTLPR. No deviation from the Hardy-Weinberg equilibrium in patients was observed. In addition, allele and genotype frequencies were similar in the two groups. Our data do not support the implication of the 5-HTT gene in the psychiatric comorbidities of NF1.

Alleles↗
PubMed2001

Quality-of-life impairment in neurofibromatosis type 1: a cross-sectional study of 128 cases.

BACKGROUND: Neurofibromatosis type 1 affects quality of life (QoL) through association with severe complications, impact on cosmetic features, and uncertainty of the effects of the disorder. OBJECTIVE: To evaluate the impact of the severity and visibility of neurofibromatosis type 1 on QoL. DESIGN: Monocenter, cross-sectional study. SETTING: One French academic dermatological and neurofibromatoses clinic. PATIENTS: A total of 128 adult patients with neurofibromatosis type 1. MAIN OUTCOME MEASURES: Evaluation of severity and visibility using, respectively, the Riccardi and Ablon scales. Evaluation of skin disease-specific and general QoL using, respectively, Skindex-France and SF-36 (Short Form 36 health survey) profiles controlled for sex, age, severity, and visibility. RESULTS: In a multiple regression model controlling for sex, age, and visibility, visibility remained independently associated with the alteration of 3 aspects of the skin disease-specific QoL (Skindex-France): emotions, physical symptoms, and functioning (P =.03, P =.009, and P =.002, respectively). Patients with more severe neurofibromatosis reported more effects on the following domains of their general health QoL (SF-36): physical function, bodily pain, general health perception, and vitality (P =.006, P =.03, P =.01, and P =.04, respectively). CONCLUSIONS: Neurofibromatosis type 1 has a significant impact on QoL through alteration of health and appearance. The consequences of visibility and severity from the viewpoint of patients can be evaluated using Skindex and the SF-36, respectively.

Activities of Daily Living↗
PubMed2001

Hemarthrosis: an unusual complication of type 1 neurofibromatosis.

Type 1 neurofibromatosis is one of the most common autosomal-dominant disorders and often includes orthopedic manifestations. We report the case of a 48-year-old woman with hemarthrosis caused by a popliteal cyst infiltrated by a diffuse neurofibroma associated with angiodysplasia. Surgical resection of this tumor was followed by postoperative hemorrhagic complications.

Female↗
PubMed2001

[Sarcoidosis: thalidomide treatment in ten patients].

BACKGROUND: Acute cutaneous sarcoidosis is generally spontaneously regressive but persistent chronic cutaneous lesions are esthetically prejudicial. There have been several case reports on thalidomide efficacy but long-term outcome is unknown. We report results in 10 cases of cutaneous sarcoidosis treated with thalidomide. PATIENTS AND METHODS: Data from ten patients with sarcoidosis treated with thalidomide between January 1998 and March 1999 were collected from delivery authorizations and analyzed. All ten patients had chronic cutaneous sarcoidosis resistant to conventional therapy. Six patients had an associated visceral localization and disease duration of 2 to 18 years (median 6 years). We considered that regression was complete when erythema and infiltration had totally disappeared, that regression was incomplete when cutaneous signs remained, and that treatment had failed when no effect was observed or when the disease worsened. RESULTS: Disease regression was noted in 7 patients for a daily dose of 1.84 mg/kg for 2.8 months. Skin lesions totally regressed in 3 patients, an incompletely in 4. Treatment failed in 3 patients. Patients were treated for 10 months (2 to 21 months). The daily dose of thalidomide was gradually reduced in 5 of 7 patients for whom treatment was effective. Three of these 5 patients relapsed and thalidomide was again given and was effective again at the same dose and after the same delay. We observed improved kidney function in one patient, improvement in nasal infiltration in one other and complete regression in 3 patients who achieved long lasting reduction in angiotensin convertase level. When treatment failed, the daily dose was 1.15 mg/kg and the treatment had to be stopped for 2 patients. Side effects were minor, excepting 2 cases of neuropathy. DISCUSSION: This open study of 10 patients treated with thalidomide showed the efficacy of a 1.84 mg/kg daily dose in 7 out of 10, but complete regression of the lesions was obtained in only 3 patients. Thalidomiide appears to suspend the disease, with relapse when the drug is discontinued and efficacy at re-introduction. This would argue against a placebo effect. The mode of action could involve immunomodulating and antiinflammatory mechanisms.

Chronic Disease↗
PubMed2001

[Large hairy pigmented spots in neurofibromatosis type 1: an atypical form of neurofibromas].

INTRODUCTION: Large hairy pigmented spots have been observed in patients with neurofibromatosis type 1. In this study we tried to determine the nature and the frequency of these hairy pigmented spots in neurofibromatosis type 1. PATIENTS AND METHODS: In patients with neurofibromatosis type 1, hairy pigmented spots with a diameter more than 3 cm were systematically notified. Realisation of the biopsy of the spot was proposed to the patient. RESULTS: Among 614 patients with neurofibromatosis type 1, seven (1.1 p. 100) had a large hairy pigmented spot. Biopsy was realized in six cases. In five cases, diagnosis was superficial and plexiform neurofibroma, the 6(th) case was a Becker's nevus. CONCLUSION: Large hairy pigmented spot is a rare aspect of superficial and plexiform neurofibroma during neurofibromatosis type 1. A biopsy may be useful if it is necessary for the disorder diagnosis.

Adolescent↗
PubMed2001

Malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1: a clinicopathologic and molecular study of 17 patients.

OBJECTIVE: To identify potential prognostic factors and criteria for early detection of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1 (NF1). DESIGN: Retrospective study of malignant peripheral nerve sheath tumors in a cohort of 395 patients with NF1 followed up between October 1, 1988, and January 1, 1999; review of the clinical and histological characteristics of treatment and course; and analysis of p53 mutations and overexpression in tumors. SETTING: Teaching hospital referral neurofibromatosis center for adults. PATIENTS: Seventeen patients with NF1 (9 males and 8 females). Mean +/- SD patient age at diagnosis was 32 +/- 14 years. MAIN OUTCOME MEASURES: (1) Clinical symptoms, (2) comparison of p53 mutations and overexpression in benign vs malignant tumors; and (3) median survival. RESULTS: Twelve patients had high-grade tumors. All tumors except 1 developed on preexisting nodular or plexiform neurofibromas. Pain and enlarging mass were the first and predominant signs. None of the benign tumors displayed significant p53 staining or p53 mutations. Six of 12 malignant tumors significantly overexpressed p53, and 4 of 6 harbored p53 missense mutations. Median survival was 18 months overall, 53 months in peripheral locations, and 21 months in axial locations. CONCLUSIONS: Malignant peripheral nerve sheath tumors are highly aggressive in NF1. They mostly arise from plexiform or nodular neurofibromas. Investigations and deep biopsy of painful and enlarging nodular or plexiform neurofibromas should be considered in patients with NF1. Late appearance of p53 mutations and overexpression precludes their use as predictive markers of malignant transformation.

Adolescent↗
PubMed2000

Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1.

Although it is well recognized that a peripheral vasculopathy may occur in patients with neurofibromatosis 1 (NF1), it is unclear whether cardiovascular abnormalities are more common. We reviewed the frequency of cardiovascular abnormalities, in particular, cardiovascular malformations (CVMs), among 2322 patients with definite NF1 in the National Neurofibromatosis Foundation International Database from 1991-98. Cardiovascular malformations were reported in 54/2322 (2.3%) of the NF1 patients, only 4 of whom had Watson syndrome or NF1-Noonan syndrome. There was a predominance of Class II "flow" defects [Clark, 1995: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. p 60-70] (43/54, 80%) among the NF1 patients with CVMs. Pulmonic stenosis, that was present in 25 NF1 patients, and aortic coarctation, that occurred in 5, constitute much larger proportions of all CVMs than expected. Of interest was the paucity of Class I conotruncal defects (2 patients with tetralogy of Fallot), and the absence of atrioventricular canal, anomalous pulmonary venous return, complex single ventricle and laterality defects. Besides the 54 patients with CVMs, there were 27 patients with other cardiac abnormalities (16 with murmur, 5 with mitral valve prolapse, 1 with intracardiac tumor, and 5 with electrocardiogram abnormalities). No patient in this study had hypertrophic cardiomyopathy. There were 16 patients who had a peripheral vascular abnormality without an intracardiac CVM, plus an additional 4 patients among those with a CVM who also had a peripheral vascular abnormality.

Aortic Coarctation↗
PubMed2000

Delays in diagnosis and melanoma prognosis (II): the role of doctors.

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.

Attitude of Health Personnel↗
PubMed2000

Delays in diagnosis and melanoma prognosis (I): the role of patients.

A prospective survey was conducted to assess the role of patients in the melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a comprehensive questionnaire including a psychological instrument. Main outcome measures were the delay before medical intervention and the tumor thickness. Of 590 melanomas, 70.8% were detected by patients and this proportion was higher in females. Relatives were involved in the detection of half of the cases. Median delays before the patient realized he had a suspicious lesion, before this lesion was seen by a doctor, and before the melanoma was removed were 4 months, 2 months, and 1 week, respectively. Delays up to several years were observed in some cases. The rate of self-detection tended to be lower, the delays before seeking medical advice to be longer, and the tumor thickness to be higher in old people, in males, in lower-educated individuals, in those living out of towns, and in people with a low awareness about melanocytic tumors than in other cases. Conversely, individuals with a high number of atypical nevi, those who were aware to be at risk, and those who regularly visited a dermatologist tended to detect their melanoma more rapidly. No specific psychological traits were associated with a late reaction, although negligence and anxiety tended to prolong the delays. Knowledge about melanoma was poor in many patients, especially in males, and wrong beliefs were widespread. This study provides the targets of future education programs.

Adolescent↗
PubMed2000

NF1 gene analysis focused on CpG-rich exons in a cohort of 93 patients with neurofibromatosis type 1.

We studied the NF1 gene in 93 unrelated patients with neurofibromatosis type1, focusing the analysis on four exons that contain the highest number of possible mutations occurring at CpG sites. We used denaturing gradient gel electrophoresis to analyse exons 16, 28, 29 and 49, which contain 45 (25%) of the 183 possible mutations that could occur at the 120 CpG dinucleotides of the coding sequence. Six different mutations were identified, five of which are novel: two truncating mutations, W1810X and 5448insG, located in exon29; two splice defects leading to exon29 skipping, 5206-2A>G and 5546G>A; and one missense mutation, L844F, located in exon16. The already described R1748X mutation located in exon29 was found in two unrelated patients. The 5546G>A and R1748X mutations are located at CpG sites, whereas the W1810X involves a CpNpG site. Four novel polymorphisms, which may be helpful for family studies, were also identified. Overall, all but one mutations were found in exon29, a result which suggests that all the CpG sites of the NF1 coding sequence do not have the same mutability, and that exon29, the most CpG-rich exon, contains mutational hotspots associated with NF1.

Adolescent↗
PubMed2000

Toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) is a rare but life-threatening adverse drug reaction. Implicated drugs are sulfonamides, anticonvulsants, allopurinol, and pyrazolone derivatives. Recently, advances in pathogenesis have been made in two directions. It is now known that (1) most patients with TEN have an abnormal metabolism to the culprit drug; and (2) the mechanism leading to epidermal necrolysis seems to be a cell-mediated cytotoxic reaction. The treatment remains symptomatic.

Humans↗
PubMed2000

Cost evaluation of the medical management of neurofibromatosis 1: a prospective study on 201 patients.

Neurofibromatosis 1 (NF1) is associated with many internal complications as well as skin manifestations, and patients may require a variety of medical and surgical interventions. We aimed to assess the medical needs of NF1 patients, and to evaluate the financial cost of the resources used for them in relation to the severity of the disease. We conducted a prospective analysis on a cohort of 201 patients in our referral centre for adults. Severity of the disease was assessed. Therapeutic management was considered as multidisciplinary if it required more than three different specialists. Plastic and dermatological surgery procedures performed were recorded. Hospital costs were computed over a 3-year period and included all hospitalization days, clinic visits and procedures performed in all departments where the patients were admitted. One hundred and thirty-seven patients had at least one out-patient procedure or one hospitalization during the follow-up period. The mean cost per patient per year was pound810 (median 240; range 0-13, 860). Multidisciplinary procedures were more frequent in moderately and severely affected NF1 patients than in milder cases (P < 0. 0001); hence, the costs for moderate and severe cases were higher than for less severe groups (P = 0.005). Plastic and/or dermatological surgery was performed with the same frequency in the different severity groups (71%). Regardless of the presence of serious intractable complications, the patients' priority is for treatment of the disfigurement due to the disease. The management of these patients can be considered relatively inexpensive from the viewpoint of the healthcare system.

Adolescent↗