Alendronate after denosumab discontinuation in women previously exposed to bisphosphonates was not effective in preventing the risk of spontaneous multiple vertebral fractures: two case reports.

At denosumab discontinuation, an antiresorptive agent is indicated to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report two cases of postmenopausal women, previously exposed to bisphosphonates, treated with alendronate at denosumab discontinuation. Alendronate was ineffective to avoid spontaneous clinical vertebral fractures. They presented three and nine spontaneous vertebral fractures 8 and 12 months after denosumab discontinuation, respectively. Ineffectiveness of alendronate was attributed to insufficient control of the rebound as assessed by B-crosslaps measures in the first case, and partially to the high risk of fractures in the later. In both situations, the increased fracture risk may have favoured these new fractures. It is urgent to define effective therapeutic strategies to avoid spontaneous vertebral fractures after denosumab discontinuation.

Spatial characterization of landscapes through multifractal analysis of DEM.

Landscape evolution is driven by abiotic, biotic, and anthropic factors. The interactions among these factors and their influence at different scales create a complex dynamic. Landscapes have been shown to exhibit numerous scaling laws, from Horton's laws to more sophisticated scaling of heights in topography and river network topology. This scaling and multiscaling analysis has the potential to characterise the landscape in terms of the statistical signature of the measure selected. The study zone is a matrix obtained from a digital elevation model (DEM) (map 10 × 10 m, and height 1 m) that corresponds to homogeneous region with respect to soil characteristics and climatology known as "Monte El Pardo" although the water level of a reservoir and the topography play a main role on its organization and evolution. We have investigated whether the multifractal analysis of a DEM shows common features that can be used to reveal the underlying patterns and information associated with the landscape of the DEM mapping and studied the influence of the water level of the reservoir on the applied analysis. The results show that the use of the multifractal approach with mean absolute gradient data is a useful tool for analysing the topography represented by the DEM.

Biochemical algorithm to identify individuals with ALPL variants among subjects with persistent hypophosphatasaemia.

BACKGROUND: Hypophosphatasia (HPP) is a rare and underdiagnosed condition characterized by deficient bone and teeth mineralization. The aim of this study was first, to evaluate the diagnostic utility of employing alkaline phosphatase (ALP) threshold levels to identify adults with variants in ALPL among individuals with persistently low ALP levels and second, to determine the value of also including its substrates (serum pyridoxal-5'-phosphate-PLP-and urinary phosphoetanolamine-PEA) for this purpose in order to create a biochemical algorithm that could facilitate the diagnostic work-up of HPP. RESULTS: The study population comprised 77 subjects with persistent hypophosphatasaemia. They were divided into two groups according to the presence (+GT) or absence (-GT) of pathogenic ALPL variants: 40 +GT and 37 -GT. Diagnostic utility measures were calculated for different ALP thresholds and Receiver Operating Characteristic (ROC) curves were employed to determine PLP and PEA optimal cut-off levels to predict the presence of variants. The optimal threshold for ALP was 25 IU/L; for PLP, 180 nmol/L and for PEA, 30 µmol/g creatinine. Biochemical predictive models were assessed using binary logistic regression analysis and bootstrapping machine learning technique and results were then validated. For ALP < 25 UI/L (model 1), the area under curve (AUC) and the 95% confidence intervals (CI) was 0.68 (95% CI 0.63-0.72) and it improved to 0.87 (95% CI 0.8-0.9), when PEA or PLP threshold levels were added (models 2 and 3), reaching 0.94 (0.91-0.97) when both substrates were included (model 4). The internal validation showed that the addition of serum PLP threshold levels to the model just including ALP improved significantly sensitivity (S) and negative predictive value (NPV) - 100%, respectively- with an accuracy (AC) of 93% in comparison to the inclusion of urinary PEA (S: 71%; NPV 75% and AC: 79%) and similar diagnostic utility measures as those observed in model 3 were detected when both substrates were added. CONCLUSIONS: In this study, we propose a biochemical predictive model based on the threshold levels of the main biochemical markers of HPP (ALP < 25 IU/L and PLP > 180 nmol/L) that when combined, seem to be very useful to identify individuals with ALPL variants.

Third cycle university studies in Europe in the field of agricultural engineering and in the emerging discipline of biosystems engineering.

The main objectives of European Thematic Network entitled 'Education and Research in Agricultural for Biosystems Engineering in Europe (ERABEE-TN)' is to initiate and contribute to the structural development and the assurance of the quality assessment of the emerging discipline of Biosystems Engineering in Europe. ERABEE is co-financed by the European Community in the framework of the LLP Programme. The partnership consists of 35 participants from 27 Erasmus countries, out of which 33 are Higher Education Area Institutions (EDU) and 2 are Student Associations (ASS). 13 Erasmus participants (e.g. Thematic Networks, Professional Associations, and Institutions from Brazil, Croatia, Russia and Serbia) are also involved in the Thematic Network through synergies. To date, very few Biosystems Engineering programs exist in Europe and those that are initiated are at a very primitive stage of development. The innovative and novel goal of the Thematic Network is to promote this critical transition, which requires major restructuring in Europe, exploiting along this direction the outcomes accomplished by its predecessor; the USAEE-TN (University Studies in Agricultural Engineering in Europe). It also aims at enhancing the compatibility among the new programmes of Biosystems Engineering, aiding their recognition and accreditation at European and International level and facilitating greater mobility of skilled personnel, researchers and students. One of the technical objectives of ERABEE is dealing with mapping and promoting the third cycle studies (including European PhDs) and supporting the integration of research at the 1st and 2nd cycle regarding European Biosystems Engineering university studies. During the winter 2008 - spring 2009 period, members of ERABEE conducted a survey on the contemporary status of doctoral studies in Europe, and on a possible scheme for promotion of cooperation and synergies in the framework of the third cycle of studies and the European Doctorate in Biosystems Engineering in Europe. This paper presents the results of the survey. The legal regulations and their extent on the different countries concerning the third cycle are presented, along with the current structure of third cycle studies. The evolution and adaptation to the new EHEA in each country is also considered. Information was also gathered on the emerging topics of the Biosystems Engineering field and how these topics could be addressed by the new doctoral programmes at the European level.

Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?

BACKGROUND: Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. RESULTS: Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. CONCLUSIONS: In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

Osteoporosis and Psoriasis. / Osteoporosis y psoriasis.

Psoriasis is a chronic inflammatory disease associated with multiple comorbidities, particularly in patients with arthritis or more severe forms of the disease. The link between all these comorbidities is probably systemic inflammation. Several recent studies have indicated that patients with psoriasis may be at an increased risk of pathologic fractures and osteoporosis. Current guidelines on comorbidities in psoriasis do not recommend assessment of bone health. In this article, we review the available evidence on the association between psoriasis and osteoporosis. We first examine the concept of osteoporosis and the role of vitaminD in bone health and then propose an algorithm for managing and treating this condition in patients with psoriasis.

Blockage of autophagic flux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B cells.

PURPOSE: Autophagy has lately emerged as an important biological process with implications in several hematological pathologies. Recently, a growing body of evidence supports a putative role of autophagy in chronic lymphocytic leukemia; however, no definitive clue has been established so far. To elucidate this issue, we have developed a pilot study to measure autophagic flux in peripheral blood mononuclear cells from chronic lymphocytic leukemia patients, and explored its correlation with classical clinical/analytical parameters. METHODS/PATIENTS: Thirty-three chronic lymphocytic leukemia patients participated in the study. Autophagic flux in peripheral blood mononuclear cells was determined by western blot measuring the levels of the proteins p62 and lipidated LC3. Moreover, p62 mRNA levels were analyzed by RT-qPCR. RESULTS: Lymphocytosis and the percentage of tumoral lymphocytes in chronic lymphocytic leukemia patients statistically correlate with a blocked autophagic flux. CONCLUSION: Alterations in autophagic flux could play an important role in the physiopathology of chronic lymphocytic leukemia.

[Parapneumonic effussion. A review of 33 cases over 6 years]. / Derrame pleural paraneumónico. Revision de 33 casos en 6 años.

UNLABELLED: The incidence of empyema thoracis in children seems to be increasing. The objective [corrected] of this study is to propose a rational initial treatment of parapneumonic effusions in order to reduce hospital stay and late-stage empyema complications. Medical records of 33 children presenting parapneumonic effusions who required any surgical therapy between 1997 and 2002 were reviewed. They were grouped as (I) successful management with chest tube, (II) successful management with intrapleural instillation of urokinase and (III) successful surgical treatment: (IIIa) thoracoscopy or (IIIb) thoracotomy. CONCLUSION: Early sonographic evaluation of parapneumonic effusions is usefull to evaluate the severity of disease and the need for surgical intervention. Thoracoscopic-assisted surgery is an effective treatment for pediatric early-stage empyema. Thoracotomy is indicated for most children with established empyema.

[Polymorphism of the gene of vitamin D receptor and bone mineral density in postmenopausal women]. / Polimorfismo del gen del receptor de la vitamina D y densidad mineral ósea en mujeres posmenopáusicas.

BACKGROUND: Conflicting results have been reported on the association between restriction fragment length polymorphism at the vitamin D receptor (VDR) gene locus and bone mineral density (BMD). Population differences in environmental factors, such as calcium intake and calcidiol levels which have strong influence in BMD, may alter this association. PATIENTS AND METHODS: We analyzed the Bsml RFLP at the eight introm of the VDR gene in a population sample (n = 204) of postmenopausal Spanish women aged 50-65 years being seen clinically and studied calcium intake (dietetic questionnaire) and biochemical parameters (PTH and calcidiol). In parallel bone densitometry were measured in lumbar spine and proximal femur. RESULTS: We identified low BMD of the proximal femur in the BB group. This effect was not observed at other body locations. The calcium intake was lees than 500 mg/day in 60% of the studied population as calcidiol levels were lower than 10 ng/l in 36% of it. The total group population with normal calcium intake (> 1,000 mg/day) showed higher BMD (proximal femur and spine) than the group with low calcium intake, this variation not being observed in group BB alleles. Interestingly, we observed significant differences in BMD proximal femur between genotype groups BB versus Bb + bb when calcidiol levels were < 10 ng/l. Moreover, within the BB subgroup, those subjects with normal calcidiol levels have higher proximal femur BMD compared with those with low calcidiol levels. CONCLUSIONS: Our results indicate an effect of the VDR genotype on BMD proximal femur which is clearly influenced by calcium intake and calcidiol serum levels.

[High prevalence of vitamin D deficiency in postmenopausal women at a rheumatology office in Madrid. Evaluation of 2 vitamin D prescription regimens]. / Alta prevalencia de deficiencia de vitamina D en mujeres posmenopáusicas de una consulta reumatológica en Madrid. Evaluación de dos pautas de prescripción de vitamina D.

BACKGROUND: Vitamin D deficiency has been frequently observed in the elderly population in Europe. However few information is available about the vitamin D status in postmenopausal women in the Mediterranean countries. The aim of this study was to evaluate the vitamin D status assessed by serum 25(OH)D3 (calcidiol) in postmenopausal women who attended a Rheumatology practice in Madrid area, and to evaluate calcidiol serum levels through one year after two forms of vitamin D administration. PATIENTS AND METHODS: Calcidiol serum levels were measured in 171 postmenopausal women (111 with osteoporosis and 60 without osteoporosis). 82 women with calcidiol serum levels < 10 ng/ml were distributed in two groups: Group I received 800 U/day of vitamin D3 associated with calcium (1 g/day) and group II, one dose of 80,000 U vitamin D orally as calcidiol and latter a daily dose of 800 U vitamin D3 plus 1 g calcium. Calcidiol serum levels were measured by RIA in both groups at basal condition and after three, six and twelve months under treatment. RESULTS: Three cut-offs were considered: 10, 15 and 20 ng/ml of calcidiol. Percentages of postmenopausal women with vitamin D deficiency for such cut-offs were: 35.3%, 64.1% and 87.1%, respectively. After three months of treatment, women from group II showed calcidiol serum levels higher than group I. At six and twelve months calcidiol serum levels were similar in both groups. CONCLUSIONS: A high prevalence of vitamin D deficiency was observed in a group of postmenopausal women who attended a rheumatology practice in Madrid area. Both forms of vitamin D administration seem not sufficient to maintain the adequate calcidiol serum levels in postmenopausal deficient women. A dose of 80,000 U of calcidiol twice a year should be considered.

[Melkersson-Rosenthal syndrome: report of a familial case]. / Síndrome de Melkersson-Rosenthal: a propósito de un caso familiar.

Melkersson-Rosenthal syndrome keeps on being a very unknown disease in our days in its etiology, prognosis and treatment. The limited prevalency of this entity makes in a great number of cases, diagnosis delates, specially when the disease doesn't manifestate in its complete presentation, characterized by the association of recurrent orofacial swelling, peripheral facial palsy and plicated tongue. In this article, we report a classic case of this neuro-muco-cutaneous disease, whose diagnosis delated, perhaps, because we loose the global dimention of the patient.

[Surgery of lung metastasis]. / La cirugía de las metástasis pulmonares.

INTRODUCTION: The 30-40% of the oncologic patients have pulmonary metastases. Lung can be the only organ affected. In selected patients, exeresis of the pulmonary nodules can mean their healing. MATERIAL AND METHODS: Between 1982-1997, twenty two patients presented metastases, 13 could be operated and 16 thoracotomies were done. There were 53% boys and 47% girls whose ages ranged from 3 to 15 years. We have considered: pulmonary tumour location, disease free interval, number of metastases, surgical technique and incomplete pulmonary tumour resection. RESULTS: Primary tumours were: Wilms tumours 23%, bone tumours 67% (Ewing and osteosarcoma). Disease free interval was < 2 years in 8 patients (61%) and > 2 years in 39%. X-Ray and CT were performed in every case and 66% presented a solitary nodule. Surgical techniques were: metastasectomy in two cases (12%), wedge resection in 8 (50%) and lobectomy in six cases (38%). We made thoracoscopy in two patients. There weren't postoperatory mortality but the patients with tumorectomy had an incomplete surgical resection. The overall survival is 54 percent and the 5 years survival is 23 percent (3 patients). CONCLUSIONS: The patients with a DFI < 2 years have a survival of 25% compared with 100% for patients who have a DFI > 2 years. The pulmonary resection in selected patients can offer better survival. We can use the thoracoscopy in same selected patients.

[The treatment of the tracheobronchomalacia in pediatric age]. / Tratamiento de la traqueobroncomalacia en la edad pediátrica.

OBJECTIVE: Aortopexy is the more extended treatment for severe tracheomalacia, when it fails, reintervention and other procedures are necessary. We present our experience in the treatment of this pathology. MATERIAL AND METHODS: Tracheomalacia, bronchomalacia and tracheobroncomalacia cases during a twelve year period (1983-1995) were reviewed (type, age, symptoms, surgical procedures and results were collected). RESULTS: Nineteen patients (9 males, 10 females) presented tracheobronchomalacia in our Hospital. Diagnosis was made by bronchoscopy in all of them: nine cases of tracheomalacia, five bronchomalacias and five suprastomal malacias were found. Mean diagnosis age was twenty four months (newborn-twelve years). Ten patients were managed nonoperatively, five with anterior cricoideal suspension and two cases were treated by aortopexy; one of them, after 2 months of respiratory stridor and recurrent respiratory arrest, needed an endoscopically placed intraluminal expandable Palmaz Prothesis. This prothesis was removed two years later. In this moment, the patient is doing well without stridor or respiratory symptoms.

First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS).

Hunter syndrome (mucopolysaccharidosis type II [MPS II], OMIM309900) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulphatase, resulting in accumulation of glycosaminoglycans (GAGs), multisystem organ failure and early death. Enzyme replacement therapy (ERT) with idursulfase is commercially available since 2007. Early access programs were established since 2005. However, limited information on the effects of ERT in young children is available to date. The aim of this analysis was therefore to determine the effects of ERT on patients younger than 5 years of age. We report data from six Spanish patients with confirmed Hunter syndrome who were younger than 5 years at the start of ERT, and had been treated with weekly intravenous infusions of idursulfase between 6 and 14 months. Baseline and treatment data were obtained from the Hunter Outcome Survey (HOS). HOS is an international database of MPS II patients on ERT or candidates to be treated, that collects data in a registry manner. HOS is supported by Shire Human Genetic Therapies, Inc. (Cambridge, MA, USA). At baseline, all patients showed neurological abnormalities, including ventriculomegaly, hydrocephaly, cerebral atrophy, perivascular changes and white matter lesions. Other signs and symptoms included thoracic deformity, otitis media, joint stiffness and hepatosplenomegaly, demonstrating that children under 5 years old can also be severely affected. ERT reduced urinary GAG levels, and reduced spleen (n = 2) and liver size (n = 1) after only 8 months. Height growth was maintained within the normal range during ERT. Joint mobility either stabilized or improved during ERT. In conclusion, this case series confirms the early onset of signs and symptoms of Hunter syndrome and provides the first evidence of ERT beneficial effects in patients less than 5 years of age. Similar efficacy and safety profiles to those seen in older children can be suggested, although further studies including a direct comparison with older patients would still be required.

Joint effects of mutation and selection on gametic frequencies in a panmictic population.

The classical theory of population genetics considers the situation when mutation rates are small relative to selection coefficients, and when selection acts only in previously mutated gametes and there is no back mutation. I have considered the effects of mutation and selection when the newly mutated gametes as well as the preexisting one are affected by selection. If the mutation rate m from A leads to a is greater than or equal to the selection coefficient, s, against a, the equilibrium frequency of A is zero. If m less than s, the equilibrium probability of A is m(1 - s)/s(1 - m). It is suggested that the solutions obtained here may be realistic in certain situations, particularly whey mutation is considered at the molecular level.

Passive mechanical properties of the aorta during pregnancy in rats.

The passive mechanical properties of the aorta from rats were investigated on in vitro preparations during pregnancy. At 0 mm Hg, volume was found to be higher in pregnancy than in control series. At the lower pressures of the hysteresis curves, Volumetric Distensibility Modulus was higher in control series than during pregnancy. Hysteresis percentage, and stress relaxation were found to be diminished during pregnancy. The water of the aortic wall was increased from the 14th day of pregnancy. This evidence suggests that during pregnancy there was an increase in volume and vessel turgidity, which could be taken in relationship with the lowering of the fibrous elements folds.

System of pleiotropic polygenes in the Cucurbitacea Ecballium elaterium (L.) Rich. related to durability and size of plant.

The statistical association between the characters "life durability of plant" and "size of plant" observed in a set of samples - cultivated forming a system of randomly balanced incomplete blocks - and corresponding to filial generations (pure, hybrid or backcross) from hybridization between the monoecious subspecies and the dioecious subspecies of the Cucurbitacea Ecballium elaterium (L.) Rich, respectively, is in concordance with the hypothesis that the system of polygenes governing the life durability of the plant in this species and the system of polygenes governing the size of the plants belong to the same system of polygenes. This system of pleiotropic polygenes governs the size and life durability of the plants at the same time.

[Continuing education in primary care: the educational needs of its professionals]. / Formación continuada en atención primaria: necesidades formativas de sus profesionales.

OBJECTIVES: To find professionals' suggestions for training contents, the value they place on various options, the difficulties they detect for attending activities and their preferences for time-table and format of courses. DESIGN: Cross-sectional, descriptive study. SETTING: Primary Care Area 7 in Madrid. PARTICIPANTS: Medical and office workers from the area (n=1,053). MAIN MEASUREMENTS: An anonymous self-filled questionnaire. RESULTS: 39% replied (46% nurses; 42% administrative assistants, and 40% doctors). The subjects for courses most often requested by doctors were dermatology, minor surgery and radiology; by nurses, emergency, functional bandages and computer skills; and by administrative assistants, computers, management of health service delivery and Internet. The continuing education options valued most highly were courses/workshops in the area's continuing education programme, self-training sessions and rotations. The main difficulties for attending courses were the lack of budget for cover and time-tables outside working hours. 42% preferred mornings; and 35%, courses lasting more than 20 hours. CONCLUSIONS: The training needs expressed by doctors and nurses are mainly clinical in content, whereas those of office staff are mainly computer-related. The most highly valued training options are the courses/workshops in the area's continuing education programme. The main difficulty for attending courses is the lack of cover for their job.

Painful shoulder: comparison of physical examination and ultrasonographic findings.

BACKGROUND: High frequency ultrasonography is an accurate non-invasive imaging technique for evaluating patients with painful shoulder. OBJECTIVE: To compare the clinical diagnosis established by a physical examination with high frequency ultrasonographic findings in patients with painful shoulder. METHODS: Thirty one consecutive patients with a first flare of shoulder pain were prospectively included in the study. All had a physical examination performed by two blinded rheumatologists. Ultrasonographic examination was carried out within one week of the physical examination by a third rheumatologist experienced in this technique who had no knowledge of the clinical findings. Ultrasonography was considered the optimal diagnostic technique. RESULTS: Clinical assessment showed low accuracy in the diagnosis of periarticular shoulder lesions. CONCLUSION: Ultrasonography should be used wherever possible to improve diagnosis and treatment of painful shoulder.