A novel approach in breast reconstruction: The extended lateral thoracic flip-over flap combined with loops and lipofilling (ELT FOLL).

INTRODUCTION: The use of the thoracodorsal musculocutaneous flap has been limited to donor site complications, whereas the thoracodorsal fasciocutaneous flap spares the muscle and limits morbidities. Our objective is to describe a new technique of breast reconstruction using an extended lateral thoracic (ELT) flip-over flap combined with loops and lipofilling (ELT FOLL) to achieve better breast remodeling. METHODS: Between 2013 and 2018, 64 patients underwent breast reconstruction using an ELT FOLL. The flap is designed in an elliptical transverse pattern and extends 2 cm lateral to the back midline up to the breast axis at the level of the inframammary fold. The surgical technique consists of an infiltration and tunnelization of the breast recipient site and surrounding area, deepithelialization of the skin paddle, and additional preparation of the flaps and loops. Liposuction is performed using the power-assisted liposuction and lipofilling technique, and lipofilling is achieved throughout the thoracic cutaneous surface of the reconstructed site, particularly into the lower quadrant of the breast. RESULTS: Among the reconstructions, 73.4% was delayed and 92.2% was unilateral. A fourth of the patients were smokers, and 39.1% received radiotherapy. The total complication rate was 8.7%, the patient's shoulder function was not affected at long term, with the DASH score rising from 6.53 preoperatively to 11.32 at 6 weeks and 7.52 at 6 months. The average operative time was 57 min, and drains were removed at day one after surgery. CONCLUSION: The ELT FOLL should be considered a simple, safe, and reliable alternative for breast reconstruction.

[Oral lesions in psoriasis]. / Manifestations buccales du psoriasis.

BACKGROUND: The literature contains little information about the incidence or prevalence of oral signs in psoriasis. The pustular forms are the most commonly incriminated, with geographic tongue being the most frequently cited oral sign. The aim of our study was to determine the various types of oral signs seen in a large population of psoriasis patients. PATIENTS AND METHODS: Four hundred psoriasis patients were recruited consecutively and a detailed oral examination performed by two clinicians. Similar examinations were performed over the same period in 1000 nonpsoriasis subjects comprising a control group in order to assess the incidence of the same oral signs in the general population. RESULTS: Comparing the two groups, fissured tongue was seen in 33.2% of psoriasis patients versus 9.9% of control subjects (P<0.0001). There was thus a highly significant (P<0.0001) correlation between geographic tongue and psoriasis (7.7% of psoriasis patients versus 1% of controls). In addition, a strong correlation was seen between the presence of pustular psoriasis and fissured tongue (83.3% of patients with pustular psoriasis versus only 30% of patients with other forms of psoriasis). DISCUSSION: Our study shows a strong correlation between psoriasis and fissured and geographic tongue, although these features are not pathognomonic for the disease. As regards geographic tongue, our results are consistent with the data in the literature. However, the prevalence of fissured tongue was considerably higher among our patients than in series published to date. These two types of sign involving the tongue, and which can occur in all forms of psoriasis, appear to be particularly strongly associated with pustular psoriasis. Patients are generally unaware of this sign and rarely complain of it.

PS-341 or a combination of arsenic trioxide and interferon-alpha inhibit growth and induce caspase-dependent apoptosis in KSHV/HHV-8-infected primary effusion lymphoma cells.

Kaposi's sarcoma (KS)-associated herpes virus (KSHV) is the causative agent of primary effusion lymphoma and of KS. Primary effusion lymphoma (PEL) is an aggressive proliferation of B cells. Conventional chemotherapy has limited benefits in PEL patients, and the prognosis is very poor. We previously reported that treatment of human T-cell leukemia virus type 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma cells either with arsenic trioxide (As) combined to interferon-alpha (IFN-alpha) or with the bortezomib (PS-341) proteasome inhibitor induces cell cycle arrest and apoptosis, partly due to the reversal of the constitutive nuclear factor-kappaB (NF-kappaB) activation. PEL cells also display an activated NF-kappaB pathway that is necessary for their survival. This prompted us to investigate the effects of PS-341, or of the As/IFN-alpha combination on PEL cells. A dramatic inhibition of cell proliferation and induction of apoptosis was observed in PS-341 and in As/IFN-alpha treated cells. This was associated with the dissipation of the mitochondrial membrane potential, cytosolic release of cytochrome c, caspase activation and was reversed by the z-VAD caspase inhibitor. PS-341 and As/IFN-alpha treatment abrogated NF-kappaB translocation to the nucleus and decreased the levels of the anti-apoptotic protein Bcl-X(L). Altogether, these results provide a rational basis for a future therapeutic use of PS-341 or combined As and IFN-alpha in PEL patients.

Protection against cephalosporin-induced lipid peroxidation and nephrotoxicity by (+)-cyanidanol-3 and vitamin E.

The ability of the clinically used cephalosporins: cephalothin, cefotaxime and cefotiam to induce lipid peroxidation (LPO) and renal damage was compared to that of nephrotoxic cephaloridine under in vivo conditions. Glutathione was measured in rat liver or in renal cortex as non-protein sulfhydryls. LPO was measured in plasma, renal cortex and liver by the generation of malondialdehyde or as the increase in renal cortical concentration of conjugated dienes. Impairment of renal function was measured as the decrease in renal cortical accumulation of the organic anion p-aminohippurate (PAH). Administration of cephalosporins to rats as a single dose (2000 mg/kg, ip) induced a significant glutathione-depletion in the renal cortex with cephaloridine, and in the liver with cephaloridine, cephalothin and cefotiam. Treatment of rats with cephaloridine, cephalothin and cefotiam (200, 500, or 1000 mg kg-1 day-1, ip) for 5 days resulted in a dose-dependent increase of LPO in the renal cortex. While cephaloridine induced the highest concentration of conjugated diene, cefotaxime had no effect. Measurements of PAH accumulation in renal cortical slices from cephalosporin-treated rats showed a dose-dependent decrease in the renal cortical accumulation of PAH. Pretreatment with the antioxidants vitamin E or cyanidanol (400 mg kg-1 day-1, ip) 1 h before treatment with cephaloridine, cephalothin or cefotiam (1000 mg kg-1 day-1, ip) for 3 days inhibited cephalosporin-induced LPO and significantly reduced the impairment of renal cortical accumulation of PAH. The potential of different cephalosporins for inducing LPO and reducing PAH accumulation was ranked as follows: cephaloridine > cephalothin > cefotiam > cefotaxime.

Effect of chronic exposure to cold on isoprenaline-induced cAMP accumulation and relaxation in the rat aorta.

Rats chronically exposed to cold (5 degrees C for 5 weeks) develop hypertension. Isoprenaline-induced vascular smooth muscle relaxation is increased in these animals. Our main objective was to compare isoprenaline-induced relaxation of aortae isolated from control and cold-acclimated rats and attempt to relate the differences to changes in receptor parameters (affinity and reserve) and signaling mechanisms. Isoprenaline (10(-9)-10(-5) M)-induced relaxation was enhanced significantly (p < 0.05) in aorta segments from cold-acclimated rats. There was a significant (p < 0.05) increase in the potency of isoprenaline but with no change in affinity. Isoprenaline produced 50% of the maximum response while occupying about 50% and about 15% of the receptors in isolated rat aorta segments from control and cold-treated rats, respectively. Forskolin and db-cAMP also concentration-dependently relaxed aorta segments from control and cold-acclimated rats. There was no difference in potency or maximum response to forskolin (which directly activates adenylyl cyclase) and db-cAMP. cAMP concentrations in the presence of isoprenaline were significantly (p < 0.05) higher in aorta segments from rats chronically exposed to cold when compared with aorta segments from control rats. These findings suggested that altered mechanisms upstream of activation of adenylyl cyclase are involved in the increased beta-adrenoceptor-induced relaxation.

Detection of a Mr 24,000 estrogen-regulated protein in human breast cancer by monoclonal antibodies.

Monoclonal antibodies have been prepared that can specifically detect an estrogen-regulated protein with a molecular weight of 24,000 in the MCF-7 human breast tumor cell line and in human breast tumor biopsies. These antibodies are of the immunoglobulin G1 subclass, exhibit a high affinity for the Mr 24,000 protein, and recognize an antigenic site that is stable to sodium dodecyl sulfate gel electrophoresis and electrophoretic transfer techniques. These monoclonal antibodies have been used to confirm estrogen regulation of the Mr 24,000 protein in MCF-7 cells and to detect Mr 24,000 protein in certain human breast tumors.

Right ventricular form and function after percutaneous atrial septal defect device closure.

OBJECTIVES: We sought to assess the right heart's response to percutaneous device closure of moderate sized atrial septal defects (ASDs) in adults over a one-year follow-up period. BACKGROUND: Percutaneous ASD device closure is a safe and effective means of reducing or eliminating interatrial shunting. The response of the adult's right heart to device closure is incompletely understood. METHODS: Forty consecutive patients had 40 device implantations (32 with the CardioSeal implant and 8 with the Amplatzer device). The patients were assessed with echocardiography, chest radiography and electrocardiography before the procedure and at 1, 6 and 12 months. RESULTS: The mean ASD size was 13+/-4 mm, and the device size ranged from 33 to 40 mm for CardioSeal and 12 to 36 mm for Amplatzer. At one month, heart size (49% vs. 46%), four-chamber right ventricular (RV) size (45 vs. 41 mm), paradoxical septal motion (60% vs. 5%), QRS duration (125 vs. 119 ms), PR interval (181 vs. 155 ms) and echocardiographically determined pulmonary artery systolic pressure decreased significantly and was maintained at 12-month follow-up. At six months, right atrial length decreased from 50 to 47 mm. At one year, 29% of patients had persistent RV enlargement. CONCLUSIONS: Right heart morphology undergoes rapid improvement within one month of defect closure, with associated mechanoelectrical benefit. A small number of patients had persistent RV enlargement or pulmonary hypertension, or both, at one year. Our data support the application of transcatheter methods in achieving excellent hemodynamic and anatomic outcomes.

Purification of an estrogen-regulated breast cancer protein by monoclonal antibody affinity chromatography.

An estrogen-regulated cytoplasmic protein has been purified from MCF-7 human breast cancer cells with anion exchange and monoclonal antibody affinity chromatographies. The purified protein has a monomeric mol wt of 28,000 and isoelectric species with pI's between 5.9 and 6.0. Amino acid analysis indicates the protein is acidic, is probably hydrophilic, and contains unusually low amounts of methionine and half cystine. This rapid, two-step procedure produces purified protein in high yield and demonstrates the power of monoclonal antibodies in protein purification.

Nucleotide sequence of a cluster of genes involved in the transformation of Haemophilus influenzae Rd.

A genetic locus implicated in the development of competence in Haemophilus influenzae Rd has been previously mapped to a 12.8-kb PstI region of the chromosome [Tomb et al., J. Bacteriol. 171 (1989) 3796-3802]. To define the boundaries of this locus and to identify the gene(s) involved in transformation, additional mini-Tn10kan mutagenesis was performed and the region containing all mutagenic insertions was sequenced. Three new transformation-deficient (Tfo-) mutants were found, bringing the number of distinct mutations mapped to this region up to eight. The transformation frequency of strains carrying the new insertions was 25- to 10(5)-fold less than wild type. The ends of the mini-Tn10kan element were used as starting points to sequence a 9.1-kb region. The position of the eight mutagenic insertions was determined and ten putative open reading frames (ORFs) were found. One of the mini-Tn10kan elements had inserted in an intergenic region while the rest had inserted in six of the ORFs. Based on the phenotypes of the mutant strains and the position of the insertions, we concluded that at least three of the genes should be involved in transformation. In addition, fourteen 9-11-bp uptake signal sequences (USS) were found, four of which were part of stem-loop structures and could function as attenuators of terminators of transcription.

Effects of Inula viscosa leaf extracts on abortion and implantation in rats.

The anti-implantation and mid-term abortifacient effects exhibited by administration of Inula viscosa leaf extracts, were studied in rats. The aqueous extract administered i.p. on day 1-6 of gestation, totally diminished fetal implantation and caused a significant (P<0.05) reduction in the number of corpora lutea and blood progesterone levels. Meanwhile, administration on day 13-15 of gestation exhibited mid-term abortion. Furthermore, petroleum ether and dichloromethane, but not methanol, extracts exhibited pronounced abortifacient effects. The results of this study are in agreement with the traditional reputation of this plant as abortifacient. Further, the plant possesses anti-implantational and luteolytic effects.

[Verrucous carcinoma of the tongue occurring on lesions of lichen planus]. / Carcinome verruqueux de la langue survenu sur des lésions de lichen plan.

BACKGROUND: Verrucous carcinoma of the oral cavity is a rare entity that was formerly controversial. Etiopathogenesis remains unclear, notably as for its possible association with lichen planus. We report a case of verrucous carcinoma occurring in lesions of lichen planus of the tongue. CASE REPORT: A 78-year old, non smoking patient, with past history of cutaneous lichen planus presented for lesions of oral lichen planus affecting both the tongue and the palate. A treatment by topical tretinoin improved him in a spectacular way and brought about a remission which lasted 5 years. A recurrence occurred when the treatment was stopped; new whitish, warty cauliflower-like lesions appeared on the tongue. A biopsy confirmed the clinical suspicion of verrucous carcinoma. A laser resection was performed. Three months later, another recurrence was observed. A chemotherapy associating isotretinoin and methotrexate eliminated all lesions. The patient's condition is considered stable, under treatment, one year later. DISCUSSION: Verrucous carcinoma is a rare slow-growing oral tumor that is chiefly exophytic and does not metastasize, but it can invade and destroy oral tissues. Its clinical presentation contrasts with benign histologic features: papillomatosis, acanthosis, dysplasia in variable degrees. The occurrence on lesions of lichen planus, although "classic", is very rarely found in the literature. The treatment is not well codified. An additional chemotherapy seems necessary to prevent recurrences.

Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature.

Primary effusion lymphoma (PEL) is a rare aggressive subset of non-Hodgkin B-cell lymphoma. It is caused by Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8). It occurs mainly, but not exclusively, in HIV-positive patients. PEL predominantly develops in serous cavities and occasionally in extracavitary regions. PEL carries a very poor prognosis with a median survival time of <6 months. Indeed, currently used treatment modalities such as CHOP chemotherapy are far from achieving complete and sustainable remission. Therefore, there is no clear standard of care established in the treatment of PEL patients, stressing the need for novel-targeted approaches. Here, we have attempted a comprehensive assessment of the treatment of PEL, discussed avant-garde therapies and updated the state of preclinical research with promising clinical applications in the field. These include inhibitors of viral replication, modulators of cell signaling and inflammation, nuclear factor kappa B (NF-κB) and histone deacetylase inhibitors, and recently the combination of arsenic trioxide and interferon-alpha. Some of these targeted therapies have not yet reached clinical studies, although others were used in a few individual case reports with low numbers of patients. We also describe the first case of a 77-year-old, HIV-negative, HHV8-positive patient diagnosed with PEL limited to the pleural and peritoneal cavities. He received lenalidomide 25 mg/day for 21 days every 28 days. Treatment was well tolerated with no side effects. He rapidly improved after 1 month of treatment and progressively achieved complete remission persistent after 18 months of therapy. We believe that this review will bridge an important gap between classical chemotherapy and modern approaches of targeted therapy. Finally, our findings warrant further evaluation of lenalidomide in future prospective clinical studies.

The inflammatory response in acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy).

Among several peroxisomal neurodegenerative disorders, the pseudoneonatal adrenoleukodystrophy (P-NALD) is characterized by the acyl-coenzyme A oxidase 1 (ACOX1) deficiency, which leads to the accumulation of very-long-chain fatty acids (VLCFA) and inflammatory demyelination. However, the components of this inflammatory process in P-NALD remain elusive. In this study, we used transcriptomic profiling and PCR array analyses to explore inflammatory gene expression in patient fibroblasts. Our results show the activation of IL-1 inflammatory pathway accompanied by the increased secretion of two IL-1 target genes, IL-6 and IL-8 cytokines. Human fibroblasts exposed to very-long-chain fatty acids exhibited increased mRNA expression of IL-1α and IL-1ß cytokines. Furthermore, expression of IL-6 and IL-8 cytokines in patient fibroblasts was down-regulated by MAPK, p38MAPK, and Jun N-terminal kinase inhibitors. Thus, the absence of acyl-coenzyme A oxidase 1 activity in P-NALD fibroblasts triggers an inflammatory process, in which the IL-1 pathway seems to be central. The use of specific kinase inhibitors may permit the modulation of the enhanced inflammatory status.

KSHV-transformed primary effusion lymphoma cells induce a VEGF-dependent angiogenesis and establish functional gap junctions with endothelial cells.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL) and of Kaposi's sarcoma. PEL is an aggressive proliferation of B cells with poor prognosis. We evaluated both in vitro and in vivo the potential role of angiogenic factors secreted by PEL cells, that is, their interaction with endothelial cells and their implication in the invasive behavior of tumoral cells. In vitro, PEL-induced angiogenesis is dependent on vascular endothelial growth factor (VEGF) and VEGF receptors. However, although PEL cells produce VEGF and basic fibroblast growth factor (b-FGF) transcripts, they only secrete VEGF in vitro. In vivo, very high levels of both VEGF and b-FGF were found in the ascitic fluid of NOD/SCID mice injected with PEL cells. We then show evidence of cell adhesion and gap junction-mediated heterocellular communication between PEL cells and endothelial cells. Finally, we show that PEL cells extravasate through the endothelial barrier and that the specific tyrosine kinase inhibitor of VEGF receptors, PTK-787/ZK-222584, the anti-VEGF antibody, bevacizumab or the gap junction inhibitor 18-alpha-glycyrrhetinic acid, partially attenuate PEL cell extravasation. Angiogenesis, cell adhesion and communication likely contribute to the development of PEL and represent potential therapeutic targets.

Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome.

Constitutive activation of the NF-kappaB pathway by the Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes. We have previously shown that Tax ubiquitylation on C-terminal lysines is critical for binding of Tax to IkappaB kinase (IKK) and its subsequent activation. Here, we report that ubiquitylated Tax is not associated with active cytosolic IKK subunits, but binds endogenous IKK-alpha, -beta, -gamma, targeting them to the centrosome. K63-ubiquitylated Tax colocalizes at the centrosome with IKK-gamma, while K48-ubiquitylated Tax is stabilized upon proteasome inhibition. Altogether, these results support a model in which K63-ubiquitylated Tax activates IKK in a centrosome-associated signalosome, leading to the production of Tax-free active cytoplasmic IKK. These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome.

Unlocking diamond's potential as an electronic material.

In this paper, we review the suitability of diamond as a semiconductor material for high-performance electronic applications. The current status of the manufacture of synthetic diamond is reviewed and assessed. In particular, we consider the quality of intrinsic material now available and the challenges in making doped structures suitable for practical devices. Two practical applications are considered in detail. First, the development of high-voltage switches capable of switching voltages in excess of 10 kV. Second, the development of diamond MESFETs for high-frequency and high-power applications. Here device data are reported showing a current density of more than 30 mA mm(-1) along with small-signal RF measurements demonstrating gigahertz operation. We conclude by considering the remaining challenges which will need to be overcome if commercially attractive diamond electronic devices are to be manufactured.