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

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

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

Next-generation analysis of trypanosomatid genome stability and instability

No abstract available

High prevalence of vertebral fractures in women with breast cancer starting aromatase inhibitor therapy

Background: The purpose of this study was to describe bone status in a large cohort of postmenopausal women with nonmetastatic breast cancer, at the initiation of aromatase inhibitor therapy.Patients and methods: A prospective, transversal and clinical study was conducted. Each woman had an extensive medical history, a biological evaluation, a bone mineral density (BMD) measurement and spinal X-rays. Results: Four hundred and ninety-seven women aged 63.8 ± 9.6 years were included in this study. Eighty-five percent of these women had a 25-OH vitamin D concentration <75 nmol/l. One hundred and fifty-six women (31.4%) had a T-score < −2 at one of the three site measurements. Ninety-five women (19.1%) had a history of nonvertebral fracture with a total of 120 fractures. Spine X-rays evaluation revealed that 20% of the women had at least one vertebral fracture. The presence of vertebral fracture was associated with nonvertebral fracture history [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1–2.4] and with spine BMD (OR 1.4, 95% CI 1.1–1.7). The prevalence of vertebral fracture reached 62.9% in women with age above 70 years and femoral T-score < −2.5. Conclusion: Before starting aromatase inhibitor therapy for breast cancer, a large proportion of women had a vitamin D insufficiency and vertebral fractures

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania, as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens