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L Thomas

Publications and source records attributed to L Thomas.

At least 19 recordsLinked to original sources
PubMed2006

The C-terminus of alpha2-antiplasmin interacts with endothelial cells.

The serpin, alpha(2)-antiplasmin (alpha(2)AP), has an extended C-terminus relative to other inhibitors. This 51-residue region contains an RGD sequence; such sequences constitute a key recognition sequence for cell adhesion, mediated through integrins. In the present study, this sequence was expressed in Escherichia coli and its binding to endothelial cells and whether binding depends on the RGD sequence was investigated. Binding to the surface of human umbilical vein endothelial cells (HUVEC-C) was observed by flow cytometry and immunohistochemistry. Binding studies on immobilised cells showed specific and RGD-dependent binding of the peptides to HUVEC-C. The binding of the wild-type peptide to the HUVEC-C was significantly higher than that of a mutant peptide, in which RGD was replaced by SAA (P < 0.05, n = 4). Similarly, ethylenediaminetetraacetic acid decreased the binding of the wild-type peptide (P < 0.05, n = 4). The binding was competed out by full-length alpha(2)AP, fibronectin and anti-alpha(5)beta(1). This is the first evidence of binding of the C-terminus of alpha(2)AP to endothelial cells via its RGD sequence, with most but not all of the binding being integrin-mediated. We speculate that this interaction with alpha(2)AP may potentially play a role in the control of cellular fibrinolysis by regulating local plasmin activity on cell surfaces.

Binding, Competitive↗
PubMed2006

The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer--results from a 4-month pre-radical prostatectomy study.

BACKGROUND: As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5alpha-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS: Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS: Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of >or=90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS: Dutasteride treatment results in similar but less marked changes compared with androgen ablation.

5-alpha Reductase Inhibitors↗
PubMed2006

muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits.

The tetrodotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that muO-conotoxin MrVIB from Conus marmoreus displays substantial selectivity for Na(v)1.8 and inhibits pain behavior in models of persistent pain. In rat sensory neurons, submicromolar concentrations of MrVIB blocked tetrodotoxin-resistant current characteristic of Na(v)1.8 but not Na(v)1.9 or tetrodotoxin-sensitive VGSC currents. MrVIB blocked human Na(v)1.8 expressed in Xenopus oocytes with selectivity at least 10-fold greater than other VGSCs. In neuropathic and chronic inflammatory pain models, allodynia and hyperalgesia were both reduced by intrathecal infusion of MrVIB (0.03-3 nmol), whereas motor side effects occurred only at 30-fold higher doses. In contrast, the nonselective VGSC blocker lignocaine displayed no selectivity for allodynia and hyperalgesia versus motor side effects. The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists.

Animals↗
PubMed2006

[Conservative and functional management for soft tissue sarcomas of the extremities: role of radiotherapy].

Recent publications have permitted to quantify the benefit of radiotherapy in the conservative treatment of soft tissue sarcoma of the limbs. The aim of this review is to focus on aspects of radiotherapy witch influence local control and functional outcome for early and late normal tissue damage. The evaluation of late effects is performed according to Soma-Lent (Subjective-Objective-Management-Analytic-Late Effects of Normal Tissues) classification. About complications, neurological complications are probably under estimated and are related to total dose of radiation therapy.

Arm↗
PubMed2006

[The French preliminary experience of the use of a seed-projector for exclusive iodine 125 prostate brachytherapy: feasibility and acute toxicity].

PURPOSE: To analyse a new technique for prostate brachytherapy with permanent Iodine implants characterized by the use of a seed projector after a 3D dosimetric peroperative treatment planning (FIRST technique). PATIENTS AND METHOD: 395 patients have been treated in France with this technique in six radiotherapy centres between November 2002 and December 2005 for a localized prostate cancer. RESULTS: Thirteen patients (3.3%) developped a urinary retention, and respectively 7.8 and 26.5% an acute RTOG grade 3 and 2 toxicity. The 6-weeks IPSS score was equal or lower to 15 in 73% with a 11 median IPSS value. A failure of the loading with the seed-projector, leading to a manual loading of the seeds, occurred in 9 patients (2.3%) in two centres, directly related to the loading procedure with the seed-projector in 5 cases. The median duration of the procedure was reduced by 30 minutes for the patients treated in 2005. CONCLUSIONS: This multicenter study establishes the feasibility of the routine use of a seed projector for permanent iodine 125 prostate implants with an initial tolerance similar to the best results published for other implants techniques.

Brachytherapy↗
PubMed2006

Abnormalities of left atrial function after cardioversion: an atrial strain rate study.

BACKGROUND AND OBJECTIVES: The role of atrial myocardial dysfunction after cardioversion is unclear. In a comparison of patients after successful cardioversion from chronic atrial fibrillation (CAF) and normal controls, we sought to determine whether Doppler-derived atrial strain rate (A-sr) could be used to measure global left atrial function and whether A-sr was reduced in patients with CAF. METHODS: A-sr was measured from the basal septal, lateral, inferior and anterior atrial walls from the apical four-chamber and two-chamber views in 37 patients with CAF who had been cardioverted to sinus rhythm and followed up for 6 months, and in a cohort of 37 healthy people. Conventional measures of atrial function included peak transmitral A-wave velocity, A-wave velocity time integral, atrial fraction and the left atrial ejection fraction. Doppler tissue imaging was used to estimate atrial contraction velocity (A' velocity). In addition to amplitude parameters, the time to peak A-sr was measured from aortic valve closure. RESULTS: Immediately after cardioversion, A-sr in the CAF cohort (baseline) was significantly lower than in controls (mean (SD) -0.53 (0.31) v -1.6 (0.75) s(-1); p<0.001); the A-sr correlated with A' velocity (r = 0.63; p<0.001) in patients. Atrial function improved over time, with maximal change observed in the initial 4 weeks after cardioversion. The time to peak A-sr was increased in the CAF group compared with controls (0.55 (0.15) v 0.46 (0.12) s), but this failed to normalise over time. CONCLUSION: A-sr is a descriptor of atrial function, which is reduced after cardioversion from CAF and subsequently recovers.

Aged↗
PubMed2006

Prospective evaluation of quality of surgery in soft tissue sarcoma.

BACKGROUND: Prospective application of the French Sarcoma Group (FSG) method of surgery reporting in soft tissue sarcoma (STS) in a single centre. METHODS: Patients with primary STS of the extremities or trunk wall consecutively operated at the same institution from January 1996 to December 2002 were evaluated for local recurrence (LR). There were 205 patients, with AJCC/UICC stages III and IV in 51% of cases. Resection types according to FSG were R0 in 147, R1 in 53 and R2 in five cases. Radiotherapy was delivered in 163 patients and chemotherapy in 103. Multivariate analysis was performed. Overall five-year survival was 75%. Median follow-up for surviving patients was 53 months. RESULTS: Actuarial five-year LR incidence was 13% in 200 patients with gross resection (R0+R1), it was 7% in R0 and 30% in R1 patients (p<0.0001). At univariate analysis, significant prognosticators for LR were age, histotype, tumour invasion, grade and resection type R. At multivariate analysis, resection R1 (relative risk (RR) 4.3, p=0.001) and grade 3 (RR 3.9, p=0.013) independently predicted LR. Combining these two variables produced three prognostic groups for LR: group 0 (no factor, n=70), group 1 (one factor, n=94) and group 2 (two factors, n=36) with five-year LR of 4%, 12% and 39%, respectively (p=6.4x10(-7)). CONCLUSION: This first prospective evaluation of surgery reporting in STS evidences a fourfold, highly discriminating difference in LR between resections R0 and R1.

Adolescent↗
PubMed2006

Influence of current on field-driven domain wall motion in permalloy nanowires from time resolved measurements of anisotropic magnetoresistance.

The motion of magnetic domain walls in permalloy nanowires is investigated by real-time resistance measurements. The domain wall velocity is measured as a function of the magnetic field in the presence of a current flowing through the nanowire. We show that the current can significantly increase or decrease the domain wall velocity, depending on its direction. These results are understood within a one-dimensional model of the domain wall dynamics which includes the spin transfer torque.

Journal Article↗
PubMed2006

Thrombotic stroke following snake bites by the "Fer-de-Lance"Bothrops lanceolatus in Martinique despite antivenom treatment: a report of three recent cases.

BACKGROUND: The severity of envenoming from Bothrops lanceolatus is determined by the development of cerebral, myocardial or pulmonary infarctions, and occasionnaly by serious local envenoming. Introduction of specific antivenom has resulted in a dramatic improvement in the prognosis of this envenoming. Against this background, we report 3 recent cases of patients bitten by B. lanceolatus who developed cerebral infarctions despite early administration of antivenom. METHODS: In 1991 a protocol was designed to apply the same evaluation and treatment to all envenomed patients. The clinical results have been continuously monitored. RESULTS: Between April 1993 and July 2003, 128 envenomed patients (age 6-83 (mean 45) years) were treated. No coagulopathy, thrombotic complication or death occurred in patients who were given early antivenom therapy--up to 6h following the bite--and 126 patients recovered. Between August 2003 and October 2004, 10 additional patients (18-66 (mean 46) years) were given antivenom at the time of admission at hospital. Of these, 3 developed cerebral infarctions within 24h. Effectiveness of antivenom was tested on mouse, and found to be lower than specified by the manufacturer. DISCUSSION: Our data shows that recently the antivenom may have lost some of its efficacy. Possible mechanisms include variability in venom composition or loss of activity of the antibodies produced more than 15 years ago. The question is whether we should attempt to produce improved antivenom. This could include activity against the venom of Bothrops caribbaeus from the neighbouring island of St Lucia, which shares a monophyletic group with B. lanceolatus and whose venom produces a similar thrombotic syndrome. CONCLUSION: Prevention of systemic vessels thrombosis remains the main therapeutic challenge of B. lanceolatus envenoming in Martinique.

Adolescent↗
PubMed2006

A marker for Stevens-Johnson syndrome ...: ethnicity matters.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse drug reactions, which can be caused by a certain number of specific drugs among which is carbamazepine, an antiepileptic agent. A very strong association of carbamazepine-induced SJS with HLA-B*1502 has recently been described in the Han Chinese population. Here in, we report preliminary results from a European study (RegiSCAR) of 12 carbamazepine-induced SJS/TEN cases (nine French and three German). Among these only four had a HLA-B*1502 allele. Remarkably, these four patients had an Asian ancestry, whereas the others did not as far as we have ascertained. This shows that although the HLA region may contain important genes for SJS, the HLA-B*1502 allele is not a universal marker for this disease and that ethnicity matters.

Adult↗
PubMed2006

[Hepatocellular carcinoma revealed by prurigo].

BACKGROUND: Paraneoplastic cutaneous manifestations associated with hepatocellular carcinoma may allow early diagnosis and curative treatment. Chronic prurigo alone may reveal hepatocellular carcinoma hepatocellular carcinoma in the absence of any other abnormal laboratory results potentially indicative of hepatic disease. CASE REPORT: A 79-year-old woman was referred to our unit for prurigo beginning 3 months earlier, occurring night and day and causing insomnia. The initial results were completely normal. In the absence of improvement under treatment with dermal corticosteroids, additional investigations were performed, in particular, abdominal ultrasound. The latter showed a liver nodule of 1.5 cm in diameter. CT scan confirmed the presence of this nodule and revealed morphological changes consistent with hepatocellular carcinoma in segment VIII. Alpha-fetoprotein was elevated. Following surgical treatment of this hepatocellular carcinoma, skin lesions regressed without any further treatment. One year later, no relapse of skin lesions was observed and the patient was in complete remission regarding hepatocellular carcinoma. DISCUSSION: Prurigo may constitute a paraneoplastic sign of hepatocarcinoma, the prognosis of which depends upon the stage at which it is discovered. For small tumors (< 3 cm), surgery may be curative. Of the few cases reported in the literature, our patient is the first to undergo curative surgery thanks to early diagnosis.

Aged↗
PubMed2006

[Pathology of the eyelid in elderly patients].

OBJECTIVE: Didactic review of the various features of eyelid pathology in elderly patients. METHODS: Illustrated review centered on diagnosis of the usual aspects and pitfalls of eyelid pathology divided into semiological chapters (tumors, blisters, erythema, etc.). RESULTS: Pathology of the eyelids in elderly patients is extremely polymorphic. It is mainly centered on skin cancers (basal cell carcinoma, squamous cell carcinoma, adnexal carcinomas, and melanoma). Most severe aspects of the inflammatory diseases of the eyelid are bullous diseases (cicatricial pemphigoid, pemphigus, Stevens-Johnson syndrome, etc.). A number of rare diseases deserve mention since their presence could lead to the diagnosis of internal or systemic diseases (dermatomyositis, necrobiotic xanthogranuloma, Erdheim-Chester, etc.). In such conditions, early diagnosis is often based on the observation of isolated periocular symptoms. CONCLUSIONS: Even though topographic dermatology is a somewhat reductive vision of skin diseases, pathology of the eyelids deserves special mention because of its polymorphism as well as its diagnostic and/or therapeutic significance.

Aged↗
PubMed2006

Fine-needle aspiration biopsy with ultrasound guidance in patients with malignant melanoma and palpable lymph nodes.

BACKGROUND: Recurrence after treatment of stage I-II melanoma involves regional lymph nodes in about 50% of patients. A reliable method is needed to evaluate lymph node status (metastatic or not) in the case of palpable lymph nodes. OBJECTIVES: To evaluate the efficiency of fine-needle aspiration biopsy (FNAB) in examining clinically detected suspicious lymph node in patients followed up after surgical removal of stage I-II melanoma. PATIENTS AND METHODS: One hundred and twenty FNABs were performed in 67 patients with a suspicious node in an open study conducted in a French melanoma regional referral centre, Hôpital de l'Hôtel-Dieu. Cytodiagnosis was classified as positive, negative, inadequate or inconclusive. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were calculated after final histopathological evaluation. RESULTS: Fifty-eight of 120 FNABs were positive (48%), 50 of 120 (42%) were negative, four of 120 (3%) were inconclusive and eight of 120 (7%) were inadequate. Among the 108 FNABs in which a definitive diagnosis could be given, sensitivity was 98.2% [95% confidence interval (CI) 90.7-99.9] and specificity was 96.1% (95% CI 86.8-98.9). CONCLUSIONS: FNAB under ultrasound guidance is an efficient tool to discriminate better between cases in which surgical treatment of the lymph node basin should be performed and patients who should return for follow-up. Surgical treatment appears to be required in cases of positive FNAB or in inconclusive cases.

Adult↗
PubMed2006

Acral lentiginous melanoma: a clinicoprognostic study of 126 cases.

BACKGROUND: Although the histopathological subtype of melanoma has not been clearly proven to carry independent prognostic significance, acral lentiginous melanoma (ALM) seems to confer a poorer prognosis mainly because disease is often more advanced at the time of diagnosis. OBJECTIVES: To investigate the distinctive epidemiological and clinical characteristics of ALM, a peculiar histological entity, and to identify prognostic factors. METHODS: We performed a register-based review of cases from a single large referral centre, the University Hospital Department of Dermatology, Lyons, France. We reviewed patient demographics, the initial presentation of the lesion, and clinical outcome. ALM-specific and disease-free survival were estimated using the KaplanMeier method and compared using the log-rank test. A Cox model was used to identify prognostic factors. RESULTS: One hundred and twenty-six patients were identified as having histopathology-proven ALM in our melanoma patient register from 1996 to 2004. There were 46 (37%) subungual ALM and 80 (63%) ALM on soles, palms and nonvolar sites. The mean age at diagnosis was 63 years. There were 44 (35%) men and 82 (65%) women, sex ratio M/F 1 : 1.86. The mean Breslow thickness was 2.51 mm (range: in situ to 20 mm). There was no evidence of overexposure to ultraviolet radiation, nor was there found a predisposing genetic trait. Only 16 (13%) patients recalled a history of trauma. Thirty-four ALM (28%) were unpigmented. The median ALM-specific and disease-free survival were 13.5 and 10.1 years, respectively. The 5-year survival rate was 76%. Multivariate analysis identified tumour thickness, male gender and amelanosis as independent clinical prognostic factors for both ALM-specific and disease-free survival. CONCLUSIONS: Our study provides specific information on the clinical characteristics and outcome of this uncommon histological subtype of melanoma. However, the pathogenesis remains unknown. Breslow thickness, male gender and amelanosis were significantly associated with a poorer prognosis.

Adult↗
PubMed2006

Schnitzler syndrome associated with systemic marginal zone B-cell lymphoma.

Schnitzler syndrome is a rare condition defined by chronic urticaria and monoclonal IgM gammopathy. Malignant evolution to Waldenström disease (WD) has been reported in several cases. We report a 49-year-old man who developed a marginal zone B-cell lymphoma (MZL) 3 years after the beginning of Schnitzler syndrome. This is the first report of MZL in association with Schnitzler syndrome. IgM gammopathy is a clue for the diagnosis of Schnitzler syndrome. This condition needs to be closely monitored; it can precede the onset of an authentic lymphoproliferative disorder including WD and rarely MZL.

Cell Transformation, Neoplastic↗