Osteomalacia in a patient with Paget's bone disease treated with long-term etidronate

SummaryA 93 year-old woman with Paget\u27s disease of bone had been treated with etidronate without interruption during 20 years. The daily dose was usual (5 mg/kg/day) but this prescription had never been stopped by her physicians. Two fractures had already occurred in pagetic (right tibia) and non pagetic bones (right fibula) within the last 2 years, and she presented rib fractures, another right tibia fracture and right femur fracture during hospitalization time. X-rays films showed major osteolysis of left ulna and right tibia. Blood samples and technetium bone scan brought no evidence for sarcoma or lytic evolution of the disease. A transiliac bone biopsy on non pagetic bone site confirmed the diagnosis of osteomalacia (increased osteoid parameters), with secondary hyperparathyroidism (hook resorption). In Paget\u27s disease of bone, continuous treatment by etidronate may induce generalized osteomalacia, and increase the risk of fracture in both pagetic and non-pagetic bones. Whereas physicians and pharmaceutical industry try to improve the observance of those drugs, this striking observation also points out that a prescription always needs to be updated

Estimation of cost-of-illness in patients with psoriasis in Switzerland

BACKGROUND: Evaluation of the current clinical treatment of psoriasis in Switzerland remains to be measured with the parameters cost-of-illness and quality of life. Objective: To obtain data on out-of-pocket expenses, costs of outpatient/office-based care and inpatient care for psoriasis, and to extrapolate total costs by state of severity to the entire Swiss population. METHODS: 1200 retrospective surveys were distributed to patient members of the Swiss Psoriasis and Vitiligo Society, and 400 surveys to office-/hospital-based Swiss dermatologists. The reference year for data collection was 2005. Patients were stratified into three subgroups according to severity of disease. Costs of inpatient care were measured by the amount of hospital days of psoriatic patients from the Swiss Federal Hospital Statistics. RESULTS: 383 patient questionnaires, and 170 cases documented by 57 dermatologists were analyzed. Out-of-pocket expenses/costs for ambulatory care per patient and year ranged from CHF 600-1100 for mild psoriasis to CHF 2400-9900 for severe psoriasis. Including costs for inpatient care of approximately CHF 60 million, the total annual costs for psoriasis in Switzerland in 2004/5 amounted to approximately CHF 314-458 million. CONCLUSIONS: Moderate-to-severe psoriasis is associated with a significant impact on the quality of life and at least 4-fold higher costs than mild psoriasis, indicating the need for efficient control of the disease. This cost-of-illness study provides specific health economic data for future healthcare decision making, particularly with the advent of new therapeutic agents for effective psoriasis control

Estimation of cost-of-illness in patients with psoriasis in Switzerland

BACKGROUND: Evaluation of the current clinical treatment of psoriasis in Switzerland remains to be measured with the parameters cost-of-illness and quality of life. Objective: To obtain data on out-of-pocket expenses, costs of outpatient/office-based care and inpatient care for psoriasis, and to extrapolate total costs by state of severity to the entire Swiss population. METHODS: 1200 retrospective surveys were distributed to patient members of the Swiss Psoriasis and Vitiligo Society, and 400 surveys to office-/hospital-based Swiss dermatologists. The reference year for data collection was 2005. Patients were stratified into three subgroups according to severity of disease. Costs of inpatient care were measured by the amount of hospital days of psoriatic patients from the Swiss Federal Hospital Statistics. RESULTS: 383 patient questionnaires, and 170 cases documented by 57 dermatologists were analyzed. Out-of-pocket expenses/costs for ambulatory care per patient and year ranged from CHF 600-1100 for mild psoriasis to CHF 2400-9900 for severe psoriasis. Including costs for inpatient care of approximately CHF 60 million, the total annual costs for psoriasis in Switzerland in 2004/5 amounted to approximately CHF 314-458 million. CONCLUSIONS: Moderate-to-severe psoriasis is associated with a significant impact on the quality of life and at least 4-fold higher costs than mild psoriasis, indicating the need for efficient control of the disease. This cost-of-illness study provides specific health economic data for future healthcare decision making, particularly with the advent of new therapeutic agents for effective psoriasis control

Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.

Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP. In this case report, a patient with PRP received outpatient treatment at a university hospital department of dermatology with ustekinumab according to the dosing regimen approved for psoriasis. Lesional skin biopsy samples were taken from this patient and 2 others with refractory PRP. Messenger RNA (mRNA) expression of proinflammatory innate and T-cell-derived cytokines were measured and compared with skin samples from patients with psoriasis and healthy donors. From 1 patient, lesional skin samples were taken before ustekinumab treatment and 4 and 28 weeks after treatment initiation. Follow-up was completed after 6 months. Subcutaneous ustekinumab, 45 mg, at weeks 0 and 4 and quarterly thereafter. The primary outcome was to determine the changes in expression of proinflammatory innate and T-cell-derived cytokines during ustekinumab therapy. The secondary objective was to evaluate the clinical and histopathologic phenotype in relation to the mRNA expression profile of proinflammatory cytokines. In lesional PRP skin samples from a single patient, upregulated expression levels were found for most proinflammatory innate cytokines, including tumor necrosis factor (TNF), IL-6, IL-12, IL-23, and IL-1β. Among adaptive T-cell cytokines, an increase of TH1 cytokines and, in particular, TH17 cytokines IL-17A, IL-17F, and IL-22 was seen in PRP. The patient with PRP who received ustekinumab showed regression of skin lesions after 2 weeks and almost complete resolution after 1 month. Clinical and histopathologic improvement paralleled the expression levels of TH17 cytokines but not of interferon-γ and TNF, which lagged behind the amelioration. In this case report, a role of the IL-23-TH17-axis in PRP was identified, suggesting a shared pathogenic inflammatory pathway with psoriasis, despite evident clinical and histopathologic differences. In addition, this report provides a rationale for targeting the IL-23-TH17-pathway as a treatment option for refractory PRP

Hydrocarbons and petroleum geology of Tierra del Fuego, Argentina

The history of the hydrocarbon exploration and present production, as well as a compilation of their main tectosedimentary features in the Argentine territory of Tierra del Fuego Island are summarized in this paper. The exploration and production of hydrocarbons in the studied region is mostly restricted to both onshore and offshore portions of the Austral-Magellan Basin. Their infil is constituted by a Late Cretaceous to Tertiary sedimentary and volcanoclastic 8,000 m thick succession deposited on a folded and eroded basement cropping out along the northern foothill of the Fueguian Andes. The main productive levels are sandy layers of the Springhill Fm and Tobífera Fm in the eroded basement highs. Also, levels of the Tertiary sequences are currently under evaluation adding an exploratory potential ranging from conventional plays related to transpression and inversion structure to new scenarios based upon tectosedimentary concepts

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections

Travelers With Cutaneous Leishmaniasis Cured Without Systemic Therapy

Guidelines recommend wound care and/or local therapy as first-line treatment for cutaneous leishmaniasis. An analysis of a referral treatment program in 135 travelers showed that this approach was feasible in 62% of patients, with positive outcome in 83% of evaluable patient

The farnesoid X receptor regulates transcription of 3 beta-hydroxysteroid dehydrogenase type 2 in human adrenal cells

Recent studies have shown that the adrenal cortex expresses high levels of farnesoid X receptor (FXR), but its function remains not known. Herein, using microarray technology, we tried to identify candidate FXR targeting genes in the adrenal glands, and showed that FXR regulates 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) expression in human adrenocortical cells. We further demonstrated that FXR stimulated HSD3B2 promoter activity and have defined the cis-element responsible for FXR regulation of HSD3B2 transcription. Transfection of H295R adrenocortical cells with FXR expression vector effectively increased FXR expression levels and additional treatment with chenodeoxycholic acid (CDCA) caused a 25-fold increase in the mRNA for organic solute transporter alpha (OSTα), a known FXR target gene. HSD3B2 mRNA levels also increased following CDCA treatment in a concentration-dependent manner. Cells transfected with a HSD3B2 promoter construct and FXR expression vector responded to CDCA with a 20-fold increase in reporter activity compared to control. Analysis of constructs containing sequential deletions of the HSD3B2 promoter suggested a putative regulatory element between -166 and -101. Mutation of an inverted repeat between -137 and -124 completely blocked CDCA/FXR induced reporter activity. Chromatin immunoprecipitation assays further confirmed the presence of a FXR response element in the HSD3B2 promoter. In view of the emerging role of FXR agonists as therapeutic treatment of diabetes and certain liver diseases, the effects of such agonists on other FXR expressing tissues should be considered. Our findings suggest that in human adrenal cells, FXR increases transcription and expression of HSD3B2. Alterations in this enzyme would influence the capacity of the adrenal gland to produce corticosteroids

Best match graphs

Best match graphs arise naturally as the first processing intermediate in algorithms for orthology detection. Let T be a phylogenetic (gene) tree T and σ an assignment of leaves of T to species. The best match graph (G,σ) is a digraph that contains an arc from x to y if the genes x and y reside in different species and y is one of possibly many (evolutionary) closest relatives of x compared to all other genes contained in the species σ(y). Here, we characterize best match graphs and show that it can be decided in cubic time and quadratic space whether (G,σ) derived from a tree in this manner. If the answer is affirmative, there is a unique least resolved tree that explains (G,σ), which can also be constructed in cubic time

Next-generation analysis of trypanosomatid genome stability and instability

No abstract available