Is hepatitis C virus NS3 protease quasispecies heterogeneity predictive of progression from cirrhosis to hepatocellular carcinoma?

We investigated whether an HCV NS3 protease quasispecies heterogeneity was associated with progression from viral cirrhosis to hepatocellular carcinoma (HCC). The NS3 protease quasispecies structure of 10 HCV-1b cirrhotic patients (controls) was compared with that of 10 paired HCV-1b cirrhotic patients who displayed progression to HCC (cases). NS3 protease genetic complexity and diversity did not differ significantly between cases and controls. Amino acid substitutions were detected at 20 (11%) and 25 (14%) sites in at least two variants of the NS3 protease in cases and controls, respectively. Significant differences in the percentage of substituted clones were observed for 10 NS3 sites. Mutations Y56F, I71V, T72I, Q86P, P89S, S101G/D, R117H, S122G/T/N, V132I and V170I were more frequently observed in the NS3 protease sequences of controls than in those of cases. Residue V107 was substituted in NS3 cases but not in controls. However, these differences did not allow the definition of a specific NS3 profile related to HCC occurrence. The NS3 secondary structure B1-1 previously identified as potentially predictive of HCC was identified with a higher frequency in cases quasispecies (84.2%) than in controls (55.9%; P < 0.05). Our results suggest that there may be a relationship to fibrosis progression when diversity parameters are considered together with secondary structure profiles. Further investigations are required to determine the cellular interactions of HCV NS3 protease in the context of carcinogenesis.

Multiple senile lentigos of the face, a skin ageing pattern resulting from a life excess of intermittent sun exposure in dark-skinned caucasians: a case-control study.

BACKGROUND: Different patterns of skin ageing can be described depending on the predominant lesions, i.e. wrinkles, laxity, atrophy, senile lentigos (SLs), etc. They may correspond to different epidemiological contexts. OBJECTIVES: To identify and assess the epidemiological factors for a skin ageing pattern characterized by a high density of SLs on the face, or 'lentigo ageing pattern' (LAP). METHODS: An age- and sex-matched case-control study was conducted in individuals aged between 60 and 80 years, comparing cases (n = 118) with a very high number of SLs on the face for their age, and controls (n = 118) with no or very few SLs for their age. The cases and controls were recruited in two hospitals. RESULTS: In univariate and multivariate analysis, LAP was associated with skin types III and IV, with frequent sunburns, and with the part of the lifetime cumulative sun exposure which was received during vacations. Conversely, there was no link with the occupational and everyday exposures and the total cumulative exposure. LAP was associated with multiple solar lentigos of the upper back. No relationship was found with postmenopausal hormonal therapy, number of naevi, or freckles. CONCLUSIONS: Different epidemiological factors may account for the different skin ageing patterns. LAP seems to develop preferentially in dark-skinned caucasians who have repeatedly received intermittent and intense sun irradiations throughout their life, and have often developed solar lentigos on the upper back earlier in life, whereas the 'prominent wrinkling' pattern is known to affect light-skinned people and smokers with a life excess of continuous exposure.

[Treatment of Hailey-Hailey disease with carbon dioxide laser vaporization]. / Traitement de la maladie de Hailey-Hailey par laser ablatif CO2.

INTRODUCTION: Only ablative methods lead to long term remission of areas affected by Hailey-Hailey disease: excision/skin graft, cryosurgery, dermabrasion... The method using the CO2 laser is a recent addition in the management of this dermatitis. We report our experience with this technique in 4 patients. PATIENTS AND METHODS: Carbon dioxide laser vaporization was proposed to 4 patients exhibiting Hailey-Hailey disease resistant to classical treatments. A test under local anesthesia was performed beforehand in all the patients. A 60 year-old man had an immediate reaction and refused to continue treatment. In the other 3 cases, the result of the test at 6 months was considered satisfactory. These patients were treated under general anesthesia in a single area of 50 to 70 cm2, and a half-body for comparison. The CO2 laser was used in pulse mode, with successive irradiations, until a homogenous, whitish-yellow aspect with first retraction was obtained. RESULTS: Although the healing delays were long (a mean of 1 month) and required major analgesics over the first few days, the cosmetic results were satisfactory and no abnormal scarring was observed. After a median follow-up of 27 months, no relapse of the disease other than punctiform elements was noted. All the patients wanted treatment of the other remaining affected areas be continued. In 2 patients, CO2 laser vaporization permitted treatment of areas not easily accessible to other ablative methods (around the mouth, the anus and the vulva) with anatomy and normal function spared. DISCUSSION: These results are globally good. Although the time to healing was long, the cosmetic and functional results were always satisfactory, without abnormal scarring. Moreover, in 2 of the patients, CO2 laser was able to treat areas inaccessible to other methods. The reason for the efficacy of ablative methods is debated. Re-epidermization with keratinocytes of appendices and not expressing the molecular defect, and the constitution of dermal cicatricial tissue, are two currently proposed hypotheses.

Severe lower limbs lymphedema following breast carcinoma treatment revealing radiation-induced constrictive pericarditis--a case report.

In patients treated for breast carcinoma, unilateral lymphedema of the upper limb is usual. However, to the authors' knowledge, lower limb lymphedema has never been reported as a complication of breast carcinoma therapy. They report here the first case of a radiation-induced constrictive pericarditis revealed by severe lower limbs lymphedema. A 60-year-old woman was treated for left breast carcinoma with quadrantectomy, axillary lymphadenectomy, and combined radio chemotherapy (60 grays). Three and a half years later she suffered from a diffuse and increasing lower limbs lymphedema, which became huge and disabling. Radiation-induced constrictive pericarditis was evidenced by right cardiac cavities catheterization. A dramatic improvement was rapidly obtained after pericardectomy. Histopathologic analysis of the pericardium did not reveal neoplastic cells. Radiation-induced constrictive pericarditis is usually responsible for lower limbs edema, but lymphedema is exceptional. This case highlights the need to search for a constrictive pericarditis also in the case of lower limbs lymphedema, particularly in a patient treated with mediastinal radiotherapy or combined radio chemotherapy.