Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease.

INTRODUCTION: We propose that MuSC-derived myoblasts in PAD have transcriptomic differences that can highlight underlying causes of ischemia-induced myopathy. METHODS: Differentiation capacity among perfused and ischemic human myoblasts was compared. Following next generation sequencing of mRNA, Ingenuity Pathway Analysis (IPA) was performed for canonical pathway enrichment. Live cell imaging and immunofluorescence were performed to determine myocyte fusion index and protein expression based on insights from IPA, specifically concerning cell cycle regulators including cell-division cycle protein 2 (CDC2) and polo-like kinase 1 (PLK1). RESULTS: Ischemic myoblasts formed attenuated myotubes indicative of reduced fusion. Additionally, myoblasts from ischemic segments showed significant differences in canonical pathways associated with PLK1 (upregulated) and G2/M DNA damage checkpoint regulation (downregulated). PLK1 inhibition with BI2536 did not affect cell viability in any group over 24 h but deterred fusion more significantly in PAD myoblasts. Furthermore, PLK1 inhibition reduced the expression of checkpoint protein CDC2 in perfused but not ischemic cells. CONCLUSION: Differentiating myoblasts derived from ischemic muscle have significant differences in gene expression including those essential to DNA-damage checkpoint regulation and cell cycle progress. DNA-damage checkpoint dysregulation may contribute to myopathy in PAD.

Nano-Leish-IL: A novel iron oxide-based nanocomposite drug platform for effective treatment of cutaneous leishmaniasis.

Kinetoplastids are infamous parasites that include trypanosomes and Leishmania species. Here, we developed an anti-Leishmania nano-drug using ultra-small functional maghemite (γ-Fe2O3) nanoparticles (NPs) that were surface-doped by [CeLn]3/4+ to enable effective binding of the polycationic polyethylenebyimine (PEI) polymer by coordinative chemistry. This resulting nano-drug is cytolytic in-vitro to both Trypanosoma brucei parasites, the causative agent of sleeping sickness, as well as to three Leishmania species. The nano-drug induces the rupture of the single lysosome present in these parasites attributed to the PEI, leading to cytolysis. To evaluate the efficacy of a "cream-based" version of the nano-drug, which was termed "Nano-Leish-IL" for topical treatment of cutaneous leishmaniasis (CL), we developed a rapid screening method utilizing T. brucei parasites involved in social motility and demonstrated that functional NPs arrested the migration of the parasites. This assay presents a surrogate system to rapidly examine the efficacy of "cream-based" drugs in topical preparations against leishmaniasis, and possibly other dermal infectious diseases. The resulting Nano-Leish-IL topical preparation eliminated L. major infection in mice. Thus, this study presents a novel efficient nano-drug targeting the single lysosome of kinetoplastid parasites.

[Periprosthetic fractures of the acetabulum: revision endoprosthetics]. / Periprothetische Frakturen des Acetabulums: Revisionsendoprothetik.

BACKGROUND: Periprosthetic acetabular fractures are an increasing severe complication in revision arthroplasty. A differentiation is made between periprosthetic acetabular fractures (acute/traumatic fractures) and insufficiency fractures (chronic fractures). OBJECTIVE: This article introduces a novel treatment algorithm that provides assistance in therapeutic decision making for implant selection and the anchoring philosophy based on diagnostic decision criteria and the relevant load-bearing osseous structures, taking the defect situation into account. MATERIAL AND METHODS: The article provides an overview of original and review articles. RESULTS: The essential criteria for decisions in treatment planning are based on the stability of the primary cup, the load-bearing ability of the main anatomical structures and the resulting defect situation. For insufficiency fractures the reason for the revision and therefore the exclusion of periprosthetic joint infections (PJI) must additionally be considered. In the case of proven PJI a two-stage or multistage prosthesis exchange must be carried out. Based on the extent of apparent bony defects and pelvic discontinuity, the spectrum of treatment options ranges up to implantation of individual patient custom-made acetabular components. DISCUSSION/CONCLUSION: This overview introduces a new treatment algorithm that provides assistance in decision making for traumatic periprosthetic acetabular fractures and insufficiency fractures. It also provides decision criteria for selection of implants and the surgical approach. Due to the complexity of revision arthroplasty often requiring specialized expertise in trauma and orthopedic surgery and experienced revision surgeons, the operative treatment of periprosthetic acetabular fractures should only be carried out in specialized orthopedic and trauma surgery centers with appropriate experience.

Ipsilateral breast cancer recurrence after Deep Inferior Epigastric Perforator (DIEP) flap reconstruction: Incidence and radiological presentation.

PURPOSE: To assess the incidence and presentation of ipsilateral cancer recurrences (ICR) after deep inferior epigastric perforator (DIEP) flap reconstruction for breast cancer. PATIENTS AND METHODS: Data of 247 consecutive women with DIEP flap reconstruction after breast cancer in our institution between 1997 and 2009 were retrospectively reviewed. RESULTS: Mean follow-up time was 4.1years±3.2 (SD) (median: 3years; range: 1month - 14years). Thirty-one patients (12.5%, 95%CI: =8.7-17.3) presented 34 relapses, in average 4.1years±2.6 after mastectomy: 14 (41%) were ipsilateral, 6 (18%) contralateral and 14 (41%) metastatic. ICRs occurred earlier (3.9 vs. 5.8years; P<0.05) than non-ICRs. Most ICRs (10/14, 71%) involved the periphery of the flap and presented as palpable nodules. The remaining (4/14, 29%) involved the axilla and 3/4 (75%) were palpable. Imaging procedures detected infra-clinical ICRs in 3 of 10 imaged patients (30%). CONCLUSION: ICRs after DIEP flap reconstruction are more frequent than contralateral recurrences suggesting the need for imaging follow-up of the reconstructed breast.

JC human polyomavirus is associated to chromosomal instability in peripheral blood lymphocytes of Hodgkin's lymphoma patients and poor clinical outcome.

BACKGROUND: B cells are potential sites for latency and reactivation of the human neurotropic JC polyomavirus (JCV). We investigated JCV and Epstein-Barr virus (EBV) status in peripheral blood lymphocytes (PBL) from 74 Hodgkin's lymphoma (HL) and 91 B-cell non-Hodgkin's lymphoma (B-NHL) patients. PATIENTS AND METHODS: JCV and EBV DNA were assessed by PCR, and FISH technique was used to localize viral infection and to estimate chromosomal instability (rogue cells, 'chromosomal aberrations') throughout evolution. The influence of viral infection and chromosomal instability on freedom from progression (FFP) was investigated in HL patients. RESULTS: PCR product sequencing of PBL identified JCV in 42 (57%) circulating lymphocytes of HL patients. FISH analysis revealed that the presence of cells with a high JCV genome copy number--associated to the presence of rogue cells and 'higher frequency of chromosomal aberrations'--increased from 15% before treatment to 52% (P < 10(-5)) after. The co-activation of JCV and EBV was independent of known prognostic parameters and associated with a shorter FFP (JCV and EBV co-activation P < 0.001, rogue cells P < 0.002). CONCLUSION: In HL, JCV activation and chromosomal instability have been identified in PBL and associated with a poorer prognosis, especially in EBV+.

Primary diffuse large B-cell non-Hodgkin lymphoma of the paranasal sinuses: a report of 14 cases.

Sinonasal lymphoma (SL) is a rare form of extranodal lymphoma. Of 33 SL cases, 14 consecutive diffuse large B-cell lymphomas were treated with CHOP (adriamycin, cyclophosphamide, vincristine and prednisone) or CHOP-like chemotherapy regimen. Ten achieved complete remission (CR) and three achieved a partial remission. With a median follow-up period of 80 months, seven patients relapsed or progressed [one case including central nervous system (CNS) progression]. Four of the relapses involved the CNS. Eight patients were alive, including seven in CR and six patients had died of their lymphoma. This observation strongly suggests that CNS prophylaxis should be used in SL.

Identification of firearms holders by the [Fe(PDT)3](+2) complex. Quantitative determination of iron transfer to the hand and its dependence on palmar moisture levels.

Quantitative data are reported for the first time on the amounts of iron, which are transferred to the hand upon holding a firearm. Iron levels between 21-315 ng/cm2 were found on volunteers' palms after a single holding of a handgun. Determination of the iron traces was accomplished spectrophotometrically using 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (PDT) as a complexing agent. The transfer of iron from firearms to the palm was found to be, by and large a chemical (dissolution) rather than mechanical dislodgement. The prime factor that determines the amount of iron transferred from the firearm to the hand is the moisture level on the palm. These findings are likely to be of importance in courts of law, as well as in the war against terrorism and serious crime.

[Air bags and eye injuries: chemical burns and major traumatic ocular lesions--a case study]. / Air bags--sécurité vitale et risques oculaires: brûlures alcalines et lésions traumatiques profondes. A propos d'un cas.

The authors report a case of bilateral eye lesions with extended visual sequelae after the inflation of a driver's airbag during a head-on collision. The superficial facial lesions were accompanied by bilateral eye lesions, reaching both the anterior and posterior segments. Bilateral periorbital palpebral hematomas; voluminous bipalpebral edema combined with severe -conjunctival edema, corneal erosions, and edema; bilateral hyphema; pupillary changes with multiple iris sphincter breaks and weak pupillary light reflex only on the right eye; retrocession of the iridocorneal angle; and on fundus examination both retinas had posterior and peripheral hemorrhages and Berlin retinal edema. Five years after the trauma and 4 years after posttraumatic surgery for cataract that had progressively appeared on the left eye, the visual acuity is 25/20 in both eyes notwithstanding a small paracentral scotoma related to a break in the Bruch membrane. A review of the literature shows several types of ophthalmological lesions related to the airbag mechanism, which after combustion of an alkaline powder inflates at a very high speed, resulting in a risk of corneal-conjunctive-palpebral alkaline burns added to an eye contusion, which may be responsible for severe lesions. The American studies distinguish three factors affecting the seriousness of these airbag accidents: (a) wearing glasses, (b) position and size of the driver, and (c) inflation force of the airbag. Wearing a seatbelt is mandatory to minimize the violence of the oculofacial impact. After facial trauma from an airbag, an ophthalmological examination is necessary to assess of the chemical burns of the tissues exposed to the alkaline powder and possible major ocular lesions.

[Mesothelioma--asbestos in Lebanon: a problem to be considered]. / Mésothéliome--asbeste au Liban: un problème à retenir.

To estimate the incidence of pleural mesothelioma and its relationship with the occupational and environmental exposure to asbestos in Chekka region. Between 1991 and 2000, 22 cases of malignant mesothelioma were diagnosed at Hôtel-Dieu de France Hospital. Eighteen cases were epidemiologically investigated. Fifteen among these 18 patients (83%) had a positive exposure history: exposure was occupational in 11 cases and environmental in 4 cases. The tumor was attributable to Eternit Company in 12 cases among the exposed 15 (80%). These 12 cases were secondary to occupational exposures in 8 and to environmental exposure in 4 cases. Mean latency period between exposition and diagnosis was 29 years. Fifteen patients died from the progression of their disease after a median survival of 8 months. The relationship between pleural mesothelioma and Eternit Company with the related occupational and environmental risk in Chekka region is obvious. The assessment of the incidence needs a national cancer registry. Despite the protective measures taken by the government since 1996, an increase in the incidence is suspected in the coming ten years because of the long latency period of the disease.

[Endoscopic evaluation of chronic human immunodeficiency virus-related diarrhea]. / La place de l'endoscopie dans le diagnostic etiologique des diarrhées chroniques des sidéens.

Chronic diarrhea is an important clinical problem in patients infected with HIV. Data assessing the diagnostic yield of upper and lower endoscopy are limited. We reported 10 cases of HIV-infected patient referred to our hospital for chronic diarrhea from March 1995 to June 1999. 60% of the pathogens were identified obviously by stool studies. Cryptosporidium and Mycobacterium avium intracellulare (MAI) were the most common organisms. In this study, endoscopy identified 2 additional cases of MAI and one of 5 cryptosporidia detected in stool. Immunologic test identified a CMV infection in one case. Stool tests and endoscopy identified obviously 80% of the pathogens. Most investigators and us agree that stool studies should be the first diagnostic test. In patients with negative stool studies, lower endoscopy is more cost-effective than upper endoscopy and indicated as an initial exam.