Use of a latest-generation vascular plug for peripheral vascular embolization with use of a diagnostic catheter: preliminary clinical experience

The latest-generation Amplatzer vascular plug (AVP), the AVP 4, is designed for embolization of smaller vessels without a sheath or guiding catheter. This study evaluated the AVP 4 in peripheral vascular embolization.

Therapeutic ultrasound for osteoarthritis of the knee or hip

Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Therapeutic ultrasound is one of several physical therapy modalities suggested for the management of pain and loss of function due to osteoarthritis (OA).

Effect of platform switching on peri-implant bone levels: a randomized clinical trial

The concept of platform switching has been introduced to implant dentistry based on observations of reduced peri-implant bone loss. However, randomized clinical trials are still lacking. This study aimed to test the hypothesis that platform switching has a positive impact on crestal bone-level changes.

Effectiveness of a 308-nm excimer laser in treatment of vitiligo: a review

Vitiligo is a relatively common acquired disorder, characterized by progressive loss of melanocytes from the epidermis and the epidermal appendages. The disease is associated with considerable morbidity because of a major impact on the quality of life. The treatment for vitiligo is generally unsatisfactory and challenging. There are a variety of therapeutic possibilities including topical corticosteroids, topical calcineurin inhibitors, as well as phototherapy with Psoralen plus UVA (PUVA), narrow-band UVB, and a 308-nm excimer laser and/or lamps. Furthermore, surgical methods encompass grafting and transplantation while depigmentation treatments and psychological support may also be considered. The objective is to assess the effect of the 380-nm excimer laser in the treatment of vitiligo based on the available studies and case series. We searched the relevant literature about vitiligo and excimer laser published between 1990 and 2012 using the MEDLINE database. We reviewed all relevant articles about 308-nm excimer laser and light sources assessing their efficacy in the management of vitiligo as well as their side effects. The value of combination treatment methods was also analyzed. The available studies provide strong evidence that the excimer laser represents the most effective approach to treat vitiligo compared to ordinary phototherapy. Excimer laser is relatively safe and effective for localized disease. UV-sensitive areas respond best as well as a short duration of the disease. More frequent treatments achieve better results. Compared to other treatment modalities, the excimer laser most likely constitutes the treatment of choice for localized vitiligo. Its efficacy can be further improved in combination with other therapies such as corticosteroids, pimecrolimus, or tacrolimus.

Age-modulated association between prefrontal NAA and the BDNF gene

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p = 0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480 × age interaction on NAA level (p = 0.031). Specifically, the effect of rs1519480 on NAA level became significant at age ⩾34.17 yr. NAA level decreased with advancing age for genotype TT (p = 0.001) but not for genotype CT (p = 0.82) or CC (p = 0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.

[Castration of calves: a survey among Swiss suckler beef farmers]

In fall 2004, a survey of a representative sample of 1185 Swiss suckler beef farmers was carried out by questionnaire (return rate 51.9%). 32.7% of the respondents castrated their calves without the help of a veterinarian, 37.8% mandated a veterinarian to carry out the castrations and 29.4% did not castrate their bull calves at all. On average, 8 calves were castrated per farm and year at an average age of 7 days when the castration was carried out by a farmer or 34 days when the castration was carried out by a veterinarian. Almost all farmers castrated their calves with the rubber ring, and a majority considered no other method as feasible. 73.9% of the veterinarians used the Burdizzo technique, 14.9% applied rubber rings, and 11.2% performed a surgical procedure. 22.6% of the farmers and 85.4% of the veterinarians used sedation; local anaesthesia was performed in 32.1% of the castrations carried out by farmers and in 84.5% of the castrations carried out by veterinarians. 65.7% of the farmers were concerned by the change of the Swiss Animal Protection Ordinance (2001), when pain relief became mandatory. 47.6% of these farmers changed their castration routine: 53.1% now mandated a veterinarian, 33.0% used sedation or local anaesthesia and 8.9% abandoned castration of their calves. 59.8% of the farmers intended to participate in a future course for laymen, to study and train the technique of local anaesthesia for castration. Castration of their calves is for many suckler beef farmers an inevitable husbandry procedure. The political goal, that all calves shall be castrated with local anaesthesia can only be reached when livestock owners are informed about the distress caused by the castration and convinced of the benefit of the local anaesthesia.Veterinarians are important information carriers in this process. The implementation also produces work, be it the more complex castration procedure or the education of the farmers who want to carry out the local anaesthesia themselves.

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials

To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus.

Alendronate with and without cholecalciferol for osteoporosis: results of a 15-week randomized controlled trial

OBJECTIVE: Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) and do not take recommended vitamin D amounts. A single tablet containing both cholecalciferol (vitamin D3) and alendronate would improve vitamin D status concurrently, with a drug shown to reduce fracture risk. This study assessed the efficacy, safety, and tolerability of a once-weekly tablet containing alendronate 70 mg and cholecalciferol 70 microg (2800 IU) (ALN + D) versus alendronate 70 mg alone (ALN). METHODS: This 15-week, randomized, double-blind, multi-center, active-controlled study was conducted during a season when 25OHD levels are declining, and patients were required to avoid sunlight and vitamin D supplements for the duration of the study. Men (n = 35) and postmenopausal women (n = 682) with osteoporosis and 25OHD >or= 9 ng/mL were randomized to ALN + D (n = 360) or ALN (n = 357). MAIN OUTCOME MEASURES: Serum 25OHD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N-telopeptide collagen cross-links (NTX). RESULTS: Serum 25OHD declined from 22.2 to 18.6 ng/mL with ALN (adjusted mean change = -3.4; 95% confidence interval [CI]: -4.0 to -2.8), and increased from 22.1 to 23.1 ng/mL with ALN + D (adjusted mean change = 1.2; 95% CI: 0.6 to 1.8). At 15 weeks, adjusted mean 25OHD was 26% higher (p < 0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 25OHD < 15 ng/mL (primary endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to 0.48 [p < 0.001]), and the RR of 25OHD < 9 ng/mL (a secondary endpoint) was reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [p < 0.001]). Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover (BSAP and NTX). CONCLUSION: In osteoporosis patients who avoided sunlight and vitamin D supplements, this once-weekly tablet containing alendronate and cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of low serum 25OHD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone.

Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies

OBJECTIVE: To estimate the prognosis over 5 years of HIV-1-infected, treatment-naive patients starting HAART, taking into account the immunological and virological response to therapy. DESIGN: A collaborative analysis of data from 12 cohorts in Europe and North America on 20,379 adults who started HAART between 1995 and 2003. METHODS: Parametric survival models were used to predict the cumulative incidence at 5 years of a new AIDS-defining event or death, and death alone, first from the start of HAART and second from 6 months after the start of HAART. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. RESULTS: During 61 798 person-years of follow-up, 1005 patients died and an additional 1303 developed AIDS. A total of 10 046 (49%) patients started HAART either with a CD4 cell count of less than 200 cells/microl or with a diagnosis of AIDS. The 5-year risk of AIDS or death (death alone) from the start of HAART ranged from 5.6 to 77% (1.8-65%), depending on age, CD4 cell count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6 months the corresponding figures were 4.1-99% for AIDS or death and 1.3-96% for death alone. CONCLUSION: On the basis of data collected routinely in HIV care, prognostic models with high discriminatory power over 5 years were developed for patients starting HAART in industrialized countries. A risk calculator that produces estimates for progression rates at years 1 to 5 after starting HAART is available from www.art-cohort-collaboration.org.

Time- and dose-related regional fluxes of tissue-type plasminogen activator in anesthetized endotoxemic pigs

BACKGROUND: Acute endotoxinemia elicits an early fibrinolytic response. This study analyzes the effects of the dose and duration of endotoxin infusion on arterial levels of tissue-type plasminogen activator (tPA) and pulmonary, mesenteric and hepatic plasma tPA fluxes. METHODS: Pigs were randomized to receive an acute, high-dose (for 6 h, n=13, high ETX) or a prolonged, low-dose (for 18 h, n=18, low ETX) infusion of endotoxin or saline vehicle alone (for 18 h, n=14, control). All animals were fluid resuscitated to maintain a normodynamic circulation. Systemic and regional blood flows were measured and arterial, pulmonary arterial, portal and hepatic venous blood samples were analyzed to calculate regional net fluxes of tPA. Plasma tumor necrosis factor (TNF-alpha) levels were analyzed. RESULTS: Mesenteric tPA release and hepatic uptake increased maximally at 1.5 h in ETX groups related to dose. Maximal mesenteric tPA release [high ETX 612 (138-1185) microg/min/kg, low ETX 72 (32-94) microg/min/kg, median+/-interquartile range] and hepatic tPA uptake [high ETX -1549 (-1134 to -2194) microg/min/kg, low ETX -153 (-105 to -307) microg/min/kg] correlated to TNF-alpha levels. Regional tPA fluxes returned to baseline levels at 6 h in both ETX groups and also remained low during sustained low ETX. No changes were observed in control animals. CONCLUSIONS: Endotoxemia induces an early increase in mesenteric tPA release and hepatic tPA uptake related to the severity of endotoxemia. The time patterns of changes in mesenteric and hepatic tPA fluxes are similar in acute high-dose endotoxemia and sustained low-dose endotoxemia.

Proteolytic processing of chemokines: implications in physiological and pathological conditions

Chemokines are small, secreted proteins that orchestrate the migration of cells, which are involved in immune defence, immune surveillance and haematopoiesis. However, chemokines are also implicated in the pathology of various inflammatory diseases, cancers and HIV. The chemokine system is considerably large and has a redundancy in the repertoire of its inflammatory mediators. Therefore, strict regulation of chemokine activity is crucial. Chemokines are the substrate for various proteases including the serine protease CD26/dipeptidyl-peptidase IV and matrix metalloproteinases. Regulation by proteolytic cleavage controls and fine-tunes chemokine function by either enhancing or reducing its chemotactic activity or receptor selectivity. Often chemokines and the proteases that regulate them are produced in the same microenvironment and expression of both may be simultaneously induced by a common stimulus enabling the rapid regulation of chemokine activity. The overall impact of cleaved chemokines in cellular responses is very complex. In this review, we will give an overview on chemokine modification and the respective chemokine modifying proteases. Furthermore, we will summarize the emerging literature describing the consequences in inflammation, haematopoiesis, cancer and HIV infection upon proteolytic chemokine processing.

Point mutations in the stem region and the fourth AAA domain of cytoplasmic dynein heavy chain partially suppress the phenotype of NUDF/LIS1 loss in Aspergillus nidulans

Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger DeltanudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the DeltanudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo.

Primary perivascular epithelioid cell tumor of the liver not related to hepatic ligaments: hepatic PEComa as an emerging entity

Primary perivascular epithelioid cell tumor (PEComa) of the liver is a very rare example of an emerging family of hepatic PEC tumors. Only few cases have been described so far. We report the case of a large but benign hepatic PEComa in a 53-year-old man without signs of tuberous sclerosis. In contrast to recently described PEC-derived liver tumors in children and young adults, this neoplasm was not related to the hepatic ligaments but had developed deeply within the liver substance. The neoplastic cells displayed the complete phenotype typical for PEComas, i.e. reactivity for several melanoma markers and for smooth muscle actin. The unique relationship of myoid tumor cells to the adventitia of blood vessels prompted us, in comparison with published findings obtained with angiomyolipomas, to comment on the possible origin of the still enigmatic perivascular epithelioid cells.