Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis

OBJECTIVE: Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). METHODS: A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). RESULTS: In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). CONCLUSION: Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

Statin therapy and the expression of genes that regulate calcium homeostasis and membrane repair in skeletal muscle

In skeletal muscle of patients with clinically diagnosed statin-associated myopathy, discrete signs of structural damage predominantly localize to the T-tubular region and are suggestive of a calcium leak. The impact of statins on skeletal muscle of non-myopathic patients is not known. We analyzed the expression of selected genes implicated in the molecular regulation of calcium and membrane repair, in lipid homeostasis, myocyte remodeling and mitochondrial function. Microscopic and gene expression analyses were performed using validated TaqMan custom arrays on skeletal muscle biopsies of 72 age-matched subjects who were receiving statin therapy (n = 38), who had discontinued therapy due to statin-associated myopathy (n = 14), and who had never undergone statin treatment (n = 20). In skeletal muscle, obtained from statin-treated, non-myopathic patients, statins caused extensive changes in the expression of genes of the calcium regulatory and the membrane repair machinery, whereas the expression of genes responsible for mitochondrial function or myocyte remodeling was unaffected. Discontinuation of treatment due to myopathic symptoms led to a normalization of gene expression levels, the genes encoding the ryanodine receptor 3, calpain 3, and dystrophin being the most notable exceptions. Hence, even in clinically asymptomatic (non-myopathic) patients, statin therapy leads to an upregulation in the expression of genes that are concerned with skeletal muscle regulation and membrane repair.

Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection

The M184V mutation decreases the replication capacity of HIV-1. This prospective study aimed to characterize the virologic and immunologic changes during monotherapy with lamivudine (3TC) in patients with limited options for a fully suppressive new therapy.

Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers

To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers.

Outcomes of antiretroviral therapy in the Swiss HIV Cohort Study: latent class analysis

An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions.

A comparison of initial antiretroviral therapy in the Swiss HIV Cohort Study and the recommendations of the International AIDS Society-USA

In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS).

Can we improve partner notification rates through expedited partner therapy in the UK? Findings from an exploratory trial of Accelerated Partner Therapy (APT)

To develop two new models of expedited partner therapy for the UK, and evaluate them for feasibility, acceptability and preliminary outcome estimates to inform the design of a randomised controlled trial (RCT).

Histomorphologic evaluation of extracorporeal shock wave therapy of the fourth metatarsal bone and the origin of the suspensory ligament in horses without lameness

OBJECTIVE: To determine via histologic examination and scintigraphy the effect of focused extracorporeal shock wave therapy (ESWT) on normal bone and the bone-ligament interface in horses. ANIMALS: 6 horses without lameness. PROCEDURE: Origins of the suspensory ligament at the metacarpus (35-mm probe depth) and fourth metatarsal bone (5-mm probe depth) were treated twice (days 0 and 16) with 2,000 shocks (energy flux density, 0.15 mJ/mm2). One forelimb and 1 hind limb were randomly treated, and the contralateral limbs served as nontreated controls. Bone scans were performed on days -1 (before ESWT), 3, 16, and 19. Histomorphologic studies of control and treated tissues were performed on day 30. RESULTS: ESWT significantly increased the number of osteoblasts but caused no damage to associated soft tissue structures and did not induce cortical microfractures. A significant correlation between osteoblast numbers and radiopharmaceutical uptake was noticed on lateral views of the hind limb on days 3 and 16 and on caudal views of the forelimb on day 3. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that ESWT has the potential to increase osteoblast numbers in horses. The correlation between increased osteoblast numbers and radio-pharmaceutical uptake 3 days and 16 days after the first ESWT suggested that stimulation of osteogenesis occurred soon after ESWT. No damage to bone or the bone-ligament interface should occur at the settings used in this study, and ESWT can therefore be administered safely in horses.

Adjunctive local antibiotic therapy in the treatment of peri-implantitis II: clinical and radiographic outcomes

AIM: To monitor over 12 months clinical and radiographic changes occurring after adjunctive local delivery of minocycline microspheres for the treatment of peri-implantitis. MATERIAL AND METHODS: In 25 partially edentulous subjects, 31 implants diagnosed with peri-implantitis were treated. Three weeks after oral hygiene instruction, mechanical debridement and local antiseptic cleansing using 0.2% chlorhexidine gel, baseline (Day 0) parameters were recorded. Minocycline microspheres (Arestin) were locally delivered to each implant site with bone loss and a probing pocket depth (PPD) >or=5 mm. Rescue therapy with Arestin was allowed at Days 180 and 270 at any site exhibiting an increase in PPD>or=2 mm from the previous visit. The following clinical parameters were recorded at four sites/implant at Day 0, 10, 30, 60, 90, 180, 270 and 360: PPD, clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PlI). RESULTS: Six implants in six subjects were either rescued or exited because of persisting active peri-implantitis. Successful implants showed a statistically significant reduction in both PPD and percentage of sites with BOP between baseline and Day 360 (P<0.05). At mesial implant sites, the mean PPD reduction amounted to 1.6 mm (95% CI: 0.9-2.2 mm, P<0.001) and was accompanied by a statistically significant reduction of the BOP value (P<0.001). Binary regression analysis showed that the clinical parameters and smoking history could not discriminate between successfully treated and rescued or exited implants at any observation time point. CONCLUSION: Non-surgical mechanical treatment of peri-implantitis lesions with adjunctive local delivery of microencapsulated minocycline led to positive effects on clinical parameters up to 12 months.

Lipid profiles for antiretroviral-naive patients starting PI- and NNRTI-based therapy in the Swiss HIV cohort study

BACKGROUND: Blood lipid abnormalities in patients on highly active antiretroviral therapy (HAART) have been associated with exposure to protease inhibitors (PIs), particularly ritonavir. First therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) leads to relatively favourable lipid profiles. We report on medium-term lipid profiles (up to 5 years) for antiretroviral-naive patients starting NNRTI- and PI-based HAART in the Swiss HIV Cohort Study. METHODS: Since April 2000, blood samples taken at visits scheduled every 6 months have been analysed for cholesterol and triglyceride concentrations. For 1065 antiretroviral-naive patients starting HAART after April 2000, we estimated changes in concentration over time using multivariate linear regression with adjustment for baseline covariates, use of lipid-lowering drugs and whether the sample was taken in a fasting state. RESULTS: Non-high density lipoprotein (HDL) cholesterol levels increase with increasing exposure to either PI- or NNRTI-based therapy, HDL cholesterol levels increase and triglyceride levels decrease with increasing exposure to NNRTI-based therapy, whereas triglyceride levels increase with increasing exposure to PI-based therapy. Between NNRTI-based therapies, there is a slight difference in triglyceride levels, which tend to increase with increasing exposure to efavirenz and to decrease with increasing exposure to nevirapine. Of the three common PI-based therapies, nelfinavir appears to have a relatively favourable lipid profile, with little change with increasing exposure. Of the other two PI therapies, lopinavir with ritonavir has a more favourable profile than indinavir with ritonavir, with smaller increases in both non-HDL cholesterol and triglycerides and an increase in HDL cholesterol. Increasing exposure to abacavir is associated with a decrease in the level of triglycerides. CONCLUSION: In general, NNRTI-based therapy is associated with a more favourable lipid profile than PI-based therapy, but different PI-based therapies are associated with very different lipid profiles. Nelfinavir appears to have a relatively favourable lipid profile. Of the two boosted PI therapies, lopinavir appears to have a more favourable lipid profile than indinavir.