Biomedical subjects
Publications and source records attributed to J Zeller.
Current therapeutic concepts for acute cerebral ischaemia and cerebral haemorrhage are summarized. Patient selection for thrombolysis, the role of stroke MRI and the choice of recanalization techniques are discussed. The treatment of intracerebral haemorrhage with particular emphasis on evacuation of haematoma and acute haemostatic therapy are discussed.
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.
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.
The increasing use of influenza virus neuraminidase (NA) inhibitors (NIs) necessitates the development of reliable methods for assessing the NI susceptibility of clinical isolates. We evaluated three NA inhibition assays against a panel of five clinical isolates each of influenza virus A/H1N1, A/H3N2, and B strains and four viruses with a defined resistance genotype (R292K, H274Y, R152K, and E119V). For fluorometric enzyme assay (FA) 1 (FA-1), 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (MUNANA) at 100 microM was used as the substrate, with pretitration of the virus input. For FA-2, MUNANA at 200 microM was used as the substrate, with a fixed 1:10 dilution of input virus. For the chemiluminescence (CL) assay, the 1,2-dioxetane derivative of sialic acid at 100 microM was used as the substrate, with pretitration of the virus. Four different operators repeated the assays several times in a blinded fashion with both zanamivir and oseltamivir carboxylate (GS4071) to determine intra- and interassay variations. Mean 50% inhibitory concentration (IC(50)) values were lower and generally less variable with the CL assay. FA-1 displayed greater variation than the CL assay or FA-2 and the highest IC(50) values with zanamivir; FA-2 showed the highest values with oseltamivir, particularly for influenza virus B, and was more variable with zanamivir than was the CL assay. All three assays detected 40-fold or greater changes in IC(50) values for the resistant viruses with at least one drug. Mixing experiments, whereby increasing fractions (0, 20, 40, 60, 80, and 100%) of NA from a known NI-resistant virus were mixed with the corresponding NI-sensitive parental NA, indicated that the resolution of IC(50) values was clearer with the CL assay than with FA-2 for two of the resistant variants (R152K and E119V). The FA and CL methods were reliable for the detection of NI resistance, but all assays have certain limitations. Based on reproducibility, ease of automation, time required for the assay, and greater sensitivity, the CL assay was selected for future susceptibility testing of influenza virus isolates circulating globally.
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.
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.
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.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
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.
Explore the source record for details and available documents.
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.
Pain related to HIV disease is frequently debilitating. Of the many pain syndromes that occur in persons with HIV, distal symmetrical polyneuropathy (DSPN) is particularly devastating. Because DSPN often responds, at best, only partially to available pharmacologic interventions, non-pharmacologic interventions need to be investigated. Vibration has been suggested to be effective for reducing pain in other populations with chronic pain. This randomized, sham-controlled, double-masked study tested the short-term efficacy of a 45-min vibration treatment for DSPN foot pain in persons infected with HIV. Vibration therapy was delivered using a portable platform foot vibrator that provided stimulation at a frequency of 60 Hz. For all patients, the control box for the vibrator emitted an audible hum and part of the control box lit up during treatment, but only patients randomized to active treatment received vibration. Pain intensity (0-10) was measured immediately prior to and after treatment. Subjects were also questioned regarding pain relief (0-100%) immediately after the treatment. The mean percentage pain relief was 61.0+/-33.1% (median 70.0; range 0-100) for all patients, 67.3+/-34.0% (median 80.0; range 0-100) for vibration patients, and 55.0+/-32.0% (median 60.0; range 0-100) for sham patients. No statistically significant differences were found between the vibration and sham groups with respect to percentage pain relief (Mann-Whitney test; P=0.19) or the pre- and post-treatment current-pain difference (Mann-Whitney test; P=0.92). These results underscore the necessity for control groups in studies of non-pharmacologic therapies for pain.
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.