PubMed Health⌕ Search

Biomedical subjects

L Machet

Publications and source records attributed to L Machet.

At least 19 recordsLinked to original sources

Pleiotrophin, a candidate gene for poor tumor vasculature and in vivo neuroblastoma sensitivity to irinotecan.

In vivo neuroblastoma (NB) xenograft model, resistant to the DNA-topoisomerase I inhibitor irinotecan (CPT-11), has been established to study resistance mechanisms acquired in a therapeutic setting. Common mechanisms of resistance were not involved in this resistance. Thus, we compared the gene expression profiles of sensitive, resistant, and reverted tumors using cDNA expression arrays. Expression of selected transcripts was confirmed by quantitative real-time PCR. We found that pleiotrophin (PTN), a heparin-binding growth factor, was the only gene significantly affected: PTN gene expression was downregulated in all resistant tumors (8-14-fold) as compared to sensitive tumors, and was increased (2-4-fold) in all reverted tumors as compared to resistant tumors. PTN thus appeared to be a likely candidate gene associated with resistance to CPT-11 in this in vivo model. To investigate the direct implication of PTN in NB, we transfected two NB cell lines with RNA interferences in order to silence PTN. PTN failed to demonstrate implication in resistance to CPT-11 in vitro but could influence sensitivity to CPT-11 exclusively through an in vivo mechanism. Indeed, vasculature was significantly enhanced in resistant NB xenografts compared to sensitive and reverted xenografts, and we suggest that PTN is acting in our resistant in vivo NB model as an angiostatic factor.

Animals↗

[Necrobiotic xanthogranuloma without monoclonal gammopathy and with a rapidly fatal outcome].

BACKGROUND: Necrobiotic xanthogranuloma is an extremely rare form of histiocytosis that presents clinically as yellowish infiltrated plaques or nodules. Ocular involvement is seen in over 80% of cases. Histopathology reveals numerous xanthomous histiocytes and collagen necrobiosis. Benign monoclonal gammopathy associated with myeloma is found in 80% of patients, but the course is normally long, with 100% survival at 10 years. CASE REPORT: A 76-year-old man presented skin lesions that subsequently became ulcerated. The clinical appearance and histopathological examination resulted in diagnosis of necrobiotic xanthogranuloma. No monoclonal gammopathy or myeloma was seen. The disease was marked by sensitivity to corticosteroids with failure of other therapies (cyclophosphamide, alpha interferon), onset ofcorticosteroid dependency, iatrogenic Cushing's syndrome and diabetes, which were in part responsible for the infectious complications and subsequent death of the patient. DISCUSSION: Necrobiotic xanthogranuloma is difficult to treat, even in the absence of myeloma or monoclonal gammopathy. Corticosteroids are probably the most efficacious treatment, but can give rise to multiple complications, resulting in this particular case in death of the patient.

Aged↗

[High-resolution ultrasonography: utility in diagnosis, treatment, and monitoring dermatologic diseases].

Although less precise than histological examination, high-resolution skin imaging is a noninvasive technique that provides complementary information to the clinical examination: the lesion's US structure as well as its lateral and depth extension. Ultrasonography helps in diagnosis and initial management by measuring melanoma thickness (so as to remove this lesion with safety margins) before destructive treatment (cryosurgery or radiotherapy), by showing tumor limits, or by detecting subclinical recurrence during the follow-up. In this paper, ultrasound images will be correlated with clinical and histological data in various clinical situations such as tumors, edema, cutaneous infiltration, sclerous tissues, hyperlaxity, and cutaneous aging.

Adolescent↗

[Recurrent Castleman's disease of the neck occurring in an infant].

INTRODUCTION: Castleman's disease is a lympho-proliferative disease of unknown cause. This rare disease, usually localized, is benign and develops in the young adult. The predominant localization is mediastinal. OBSERVATION: A 15 month-old infant was referred for a left latero-cervical mass that had developed since the age of 3 months. Other than this, the clinical examination was normal. Sonography, x-ray and tomodensitometry confirmed the unique nature of the lesion and the absence of loco-regional invasion. Histology following surgical exeresis found a nodule with multiple pseudo-follicular structures. These mitosis-rich structures were arranged concentrically around a vessel and were bordered by small lymphocytes forming a crown. This histological aspect corresponded to Castleman's disease in its vascular hyaline form. Local recurrence was reported twice, 2 and 8 years later and was treated each time with surgical exeresis. Histological examination was always similar to the first. DISCUSSION: Castleman's disease has rarely been reported in infants. The cervical location, at whatever age, is far rarer than the mediastinal form. Supplementary examinations are not always of interest and basically provide information on the isolated or multicentric nature. Surgical exeresis was justified because of the diagnostic doubts and the risk of compression. Diagnosis is based on anatomopathology. Relapses have rarely been described in the literature and raise the question of the potential malignant transformation after several relapses.

Castleman Disease↗

[Paraneoplastic pemphigus revealing dendritic cell sarcoma originating from Castleman's disease of the neck].

INTRODUCTION: Paraneoplastic pemphigus is associated with Castleman's disease. We report a case of paraneoplastic pemphigus at the stage of the sarcomatous transformation of Castleman's disease, present for many years but without concomitant paraneoplastic pemphigus. The pemphigus was manifested by the most unusual, exclusive, involvement of the mucosa of the mouth and lung. OBSERVATION: A 32 year-old man suffering from extensive ulceration of the oral mucosa was hospitalized in December 2000 for alteration in his general status of health and acute respiratory failure. The search for intercellular anti-substance antibodies on rat spleen was positive, corresponding to anti-envoplakin IgG and leading to the diagnosis of paraneoplastic pemphigus. The thoracic x-ray and scan revealed a hilum tumor, the histological examination of which confirmed the diagnosis of Castleman's disease concomitant to sarcomatous transformation. Following surgical treatment, the respiratory failure worsened. The patient improved with systemic corticosteroids at the dose of 2 mg/kg/d and chemotherapy was initiated. The patient died suddenly within the context of acute respiratory failure, three months after surgery. DISCUSSION: This is a case of paraneoplastic pemphigus of unusual clinical and biological expression: exclusively mucosal involvement with obliterating bronchiolitis, explained by the isolated presence of antibodies recognizing envoplakin, without anti-desmoglein. The transformation of the Castleman tumor into a sarcoma may have unmasked intra-cellular antigens (plakins), initiating the specific immune reaction.

Adrenal Cortex Hormones↗

[Pellagra and panniculitis induced by chronic bacterial colonisation of the small intestine].

INTRODUCTION: Pellagra is an exceptional disorder in France. The classical description of pellagra associates a photoinduced rash with neurological impairment and intestinal dysfunction. Without adapted treatment, the progression is fatal. CASE REPORT: A 62 year-old women developed a photoinduced rash, composed of circular and erythematous elements with pustular edges. She also had panniculitis, peripheral neuropathy, depressive mood and diarrhea. Her medical past was marked by epilepsy treated with sodium valproate and hydantoin. Biological exams revealed lowered plasma levels of vitamins PP, B1, B6 and zinc, secondary to intestinal impairment induced by bacteria proliferating in the small intestine. The rash resolved with vitamin PP and zinc supplementation. The bacterial colonisation was improved by long-term, sequential antibiotics. DISCUSSION: We report a rare clinical form of pellagroid rash. The rash was induced by chronic malabsorption resulting from excessive bacterial proliferation in the diverticules of the small intestine. The antiepileptic treatment could have facilitated vitamin PP et zinc deficiency. Panniculitis was related to the bacterial proliferation. We discuss in this paper the relationship between some vitamin deficiencies, their clinical manifestations and the direct role of intestinal bacterial proliferation in the cutaneous manifestations.

Anti-Bacterial Agents↗

Is ultrasound lymph node examination superior to clinical examination in melanoma follow-up? A monocentre cohort study of 373 patients.

BACKGROUND: There is still lack of consensus regarding the most effective follow-up for stage I and II melanoma patients although some consensus conferences have provided guidelines stating that clinical examination should be the standard. OBJECTIVES: Our aim was to study the value of adding ultrasound lymph node examination (7.5 MHz) to the routine clinical examination recommended by French guidelines in melanoma follow-up. METHODS: A cohort of melanoma patients was enrolled between 1 July 1995 and 1 July 2000 in a follow-up protocol including clinical examination performed four times a year for thick melanomas (Breslow index > or = 1.5 mm) and twice a year for thin melanomas (Breslow index < 1.5 mm) according to French guidelines, and ultrasound lymph node examination performed every 6 months for thick melanomas and every year for thin melanomas. Follow-up was continued up to 1 July 2003. When clinical or ultrasound examination indicated signs of node recurrence, surgical biopsy of the involved node was performed. When ultrasound examination was only suspicious, another ultrasound examination was performed within the following 3 months. The results of both clinical and ultrasound examinations were compared with histopathology examination when node biopsy was performed. RESULTS: Ultrasound follow-up was performed for 373 patients (213 females and 160 males). Mean age at diagnosis of melanoma was 59 years (range 14-90, SD 15). In total, 1909 ultrasound examinations combined with clinical examination were analysed. Node biopsy was performed in 65 patients and demonstrated melanoma metastases in 54. Sensitivity of clinical examination and ultrasound examination was 71.4%[95% confidence interval (CI) 55.4-84.3] and 92.9 (95% CI 80.5-98.5), respectively, P = 0.02. Specificity of clinical examination and ultrasound examination was 99.6% (95% CI 99.2-99.8) and 97.8% (95% CI 97.0-98.4), respectively. Despite this apparent superiority of ultrasound examination over palpation, only 7.2% of the patients really benefited from ultrasound examination (earlier lymph node metastasis detection or avoidance of unnecessary surgery), while 5.9% had some deleterious effect from ultrasound examination (unnecessary stress caused by repetition of ultrasound examination for benign lymph nodes, useless removal of benign lymph node). CONCLUSIONS: This study confirms the greater sensitivity of ultrasound examination to clinical examination in the diagnosis of node metastases from cutaneous melanoma. However, the place of ultrasound in routine follow-up is at least questionable as only a very small proportion of patients (1.3%) really benefited from adding ultrasound examination to clinical examination.

Adolescent↗

Intralesional therapy with anti-CD20 monoclonal antibody rituximab: local and systemic efficacy in primary cutaneous B-cell lymphoma.

Rituximab (MabThera, Roche) is a chimeric monoclonal antibody directed against the CD20 antigen. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. We report the use of intralesional injections of rituximab into some but not all cutaneous lesions in a patient with multiple primary cutaneous follicular centre B-cell lymphoma. This treatment resulted in tumour regression, even of the lesions that had not been injected. We therefore hypothesize that there is systemic diffusion of rituximab from injected sites despite the low doses injected locally, or the induction of a specific antitumour immune response acting systemically.

Adult↗

[Atopic dermatitis: which are the diagnostic criteria used in medical literature?].

INTRODUCTION: Diagnosis of atopic dermatitis currently relies on diagnostic criteria scales developed by Hanifin and Rafka in 1980 and by the "United Kingdom Working party" in 1994. Some authors have proposed: "AEDS" [sM1] and "Atopiform Dermatitis", which has led to the distinction between different sub-populations and the exclusion of certain diseases from the diagnosis of atopic dermatitis. The aim of our study was to collect the criteria retained in the scientific medical literature during the year 2002 for the definition of atopic dermatitis and to try to understand not only the interest but also the questions that the various definitions lead to. METHOD: A PubMed research was launched with the key word "atopic dermatitis" from January to September of 2002. All the scientific articles either in French or in English were studied. RESULTS: Hanifin and Rafka's criteria were selected in 44 p. 100 of the scientific articles, and the "United Kingdom Working Party" criteria in 12 p. 100. Personal definitions were used in 21 p. 100 of the articles; these were based on the level of total and specific IgE or on personal clinical criteria. For twenty-three p. 100 of the authors, the definition of atopic dermatitis was not specified. DISCUSSION: There was not just one definition of atopic dermatitis. This may affect the interpretation of diagnostic or therapeutic papers concerning the disease, because there has been no proof that these definitions cover the same population of patients.

Dermatitis, Atopic↗

[Hypertrophic cardiomyopathy associated with oral corticosteroid therapy for palpebral hemangioma].

INTRODUCTION: Systemic corticosteroid therapy is the usual treatment for hemangioma with vascular risk. Tolerance to such treatment is usually good. OBSERVATION: A two Month-old girl presented with a hemangioma of the lower right eyelid that had developed since she was 15 days old. Treatment with betamethasone at the dose of 0.3 mg/kg/day was prescribed because of the risk of alteration in sight. The treatment was highly effective. The discovery of a systolic cardiac murmur motivated a cardiac sonography that showed signs of an obstructive hypertrophic myocardiopathy. The progressive reduction of the corticosteroids led to the regression of this disease. DISCUSSION: The onset of a cardiomyopathy during systemic corticosteroid therapy has only been reported exceptionally in the literature. There is little known of the risks. When in doubt, clinical and sonographic monitoring is probably necessary. In the case of the appearance of a cardiac murmur, the sonography is crucial.

Administration, Oral↗

[Agranular CD4+ CD56+ CD123+ hematodermic neoplasm (blastic NK-cell lymphoma) revealed by cutaneous localization: 2 cases].

BACKGROUND: Agranular CD4+ CD56+ hematodermic neoplasm (blastic NK-cell lymphoma) has been recently described. The skin is often the first organ involved. OBSERVATIONS: Two old men of respectively 70 and 77 years consulted for infiltrated cutaneous lesions. Preliminary histological examination of cutaneous biopsy taken in both patients showed a malignant proliferation suggesting a cutaneous lymphoma, and the patients were referred. Histological examination of new biopsies showed a very similar proliferation in the 2 cases of monotonous medium-sized mononuclear cells without expression of the common antigens CD3 and CD20 and the expression of CD4, CD56, and CD123. No rearrangement of the T-cell receptor gene or the immunoglobulin heavy chain gene were evidenced. No extracutaneous involvement was initially detected in the first patient. Thrombocytopenia associated with the abnormal presence of 15 p. 100 of circulating CD4+ CD56+ cells was initially found in the second patient. The first patient was treated with chemotherapy, with complete remission. A cutaneous relapse promptly occurred, followed by bone and cerebral localizations. The patient died one year after the diagnosis of the disease, in spite of intensification of the treatment. Treatment is still ongoing in the second patient. COMMENTS: The histological presentation of these two patients was very similar with an unusual phenotype of tumor cells expressing CD4, CD56, CD123, but not expressing CD3 and CD20. Some cases have been published under the "term of blastic NK lymphoma" which is the actual term for the disease in the WHO classification. However, the tumor cells derive from the dendritic plasmacytoid cells, also called type 2 dendritic cells, and perhaps from a common precursor to lymphocyte T and dendritic plasmacytoid cells. In spite of complete cutaneous response in the 2 cases presented, as in other reports, extra-cutaneous involvement occurs quickly. Overall survival is usually poor since nearly all the patients died in less than 3 years. This justifies attempting aggressive protocols, with bone marrow allograft in the younger patients.

Aged↗

A high prevalence of sensitization still persists in leg ulcer patients: a retrospective series of 106 patients tested between 2001 and 2002 and a meta-analysis of 1975-2003 data.

BACKGROUND: Sensitization to topical treatments used in leg ulcers is common. Questioning and patch testing are used to identify causative drugs or dressings. OBJECTIVES: To study the current frequency of sensitization in our centre, to analyse previously published studies, and to compare sensitization in recent years with studies published before 1990. METHODS: A retrospective study was undertaken of all patients admitted with leg ulcers in 2001 and 2002. Of the files of 235 patients with leg ulcers reviewed, we identified 106 patients (group A) who had been patch tested in our institution between 2001 and 2002 with the European standard series and an additional series. The frequency of sensitization was compared with an earlier unpublished retrospective study in our centre of 36 leg ulcer patients tested in 1988 (group B), with a group of unselected contact dermatitis patients tested between 1 January 1997 and 31 December 2000 in our centre (group C), and with results published in the literature. We performed a computerized database search of MEDLINE and compared results obtained in recent years with those obtained before 1990 to obtain evidence of changing trends. RESULTS: Seventy-five per cent of the 106 patients had at least one positive reaction, and 57% had two or more positive reactions. Balsam of Peru was positive in 40% of cases, followed by lanolin (21%), fragrance mix (18%), trichlocarban (13%), colophony (11%), Cetavlon (cetrimide cream) (9%) and neomycin (9%). Thirty-five of the 36 group B patients had at least one positive reaction. Lanolin was the most frequent (31%), followed by balsam of Peru (22%), Cetavlon (19%), colophony (14%), terebenthene (14%), quinoline mix (11%) and benzocaine (8%). Two hundred and eighty-six of 526 patients of group C were positive in at least one test (54.4%). Three allergens gave a sensitization rate >10%: balsam of Peru (12.5%), fragrance mix (15.2%) and nickel sulphate (21.1%). Review of the literature and calculation of sensitization rates in a pool of 3043 patients extracted from 24 series, plus our own, showed persistence of high sensitization rates and a significant (8.5%) increase in sensitization between the two periods compared. There was a decrease in sensitivity to lanolin, constant sensitization to aminoglycosides, a slight increase in sensitivity to thiuram mix and glucocorticoids, and a marked increase in sensitivity to balsam of Peru in France. Newer topical treatments and dressings showed very low rates of sensitivity with the exception of hydrogels. CONCLUSIONS: Despite warnings, sensitization to topical treatments for leg ulcers is still frequent and, moreover, continues to increase, some variations reflecting local nursing practices and variations in topical treatment available. Although a decrease in sensitization rate with lanolin has been observed throughout the world, no decrease in sensitization rate has been demonstrated with aminoglycosides, and sensitization to glucocorticoids, thiuram mix and new products (hydrogels) is now increasingly being reported.

Administration, Cutaneous↗

Relevance of vertical growth pattern in thin level II cutaneous superficial spreading melanomas.

Thin (<or=0.76 mm) level II cutaneous superficial spreading melanomas (SSMs) are known to be of excellent prognosis and very few recur, metastasize, or are lethal. Although many prognostic features at this stage have been studied, none appears to be statistically significant. The concept of tumor growth phase is correlated with Clark's level except for level II. SSM level II show either an invasive vertical growth phase or an invasive radial growth phase. The aim of our study (retrospective, multicenter, and case-control type) was to investigate the prognostic impact of vertical growth phase in thin level II cutaneous SSM. We identified 12 patients of poor outcome with complete initial excision. Each case was matched with three controls for gender, age, location, tumor thickness, and follow-up period since diagnosis. Independent pathologists studied all cases and controls. Univariate analyses were performed with a conditional logistic regression method. A kappa test was used to assess reproducibility between pathologists. Our study is the first and largest that shows that vertical growth phase is the only statistically significant prognostic factor for thin level II cutaneous SSM. We propose that growth phase evaluation (a minimum of eight serial sections being mandatory not to underdiagnose vertical growth phase) should be added to the recommendations for melanoma histologic report, at least for level II SSM.

Adult↗

[Contribution of lymphoscintigraphy in the exploration of lymphedema in children].

OBJECTIVES: The objectives of this work were a) to assess the feasibility of lymphoscintigraphy in very young children, and b) to assess its usefulness in understanding the underlying pathophysiology. PATIENTS AND METHODS: Forty-one children (age range 3 months-16 years) with primary lymphedema of the lower and/or upper limbs underwent lymphosinctigraphy using 99mTC-labeled colloid (Nanocis or Nanocol) injected subcutaneous at the foot and/or hand level. Recording time, which depended on the child's age, included at least static images during the thirty minutes following injection and four hours later. RESULTS: Abnormal activity of the lymph collectors, nodes, and interstitial space were analyzed according to age (> or < 2 years). Abnormal findings were classed as simple hypoplasia (n=18) or other type of lymph disease: diffuse lymphatic dysplasia (n=6), mixed vascular dysmorphism (n=5), amniotic bride disease (n=1), and hypoplasia revealed by occurrence of a minor factor (n=11). These observations demonstrate the role of lymphoscintigraphy in the diagnosis and prognostic evaluation of lymphedema in children. CONCLUSION: Lymphoscintigraphy is a useful technique for very young children with lymphedema providing further information contributing to overall exploration.

Adolescent↗

Phonophoresis: efficiency, mechanisms and skin tolerance.

Phonophoresis or sonophoresis is the use of ultrasound to increase percutaneous absorption of a drug. The technique has been widely used in sports medicine since the sixties. Controlled studies in humans in vivo have demonstrated absence or mild effects of the technique with the parameters currently used (frequency 1-3 MHz, intensity 1-2 W/cm(2), duration 5-10 mins, continuous or pulse mode). However, it was demonstrated in 1995 that administration of macromolecules with conserved biological activity was feasible in animals in vivo using low frequency ultrasound. This led to new research into this method of transdermal administration. The aim of this review is to present the main findings published with low frequency and high frequency ultrasound over the last ten years, and to discuss the respective roles of thermal, cavitational and non-cavitational effects on the reduction of the skin barrier. Particular attention is paid to the biological effects on living skin which might be of importance for tolerance and practical use in humans.

Administration, Cutaneous↗