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Juvenile, 1-g Colossoma macropomum (Cuvier) were fed two different diets: one with fish meal and another with soya meal as the main dietary protein source. Both diets were provided at ad libitum feeding level, and at two restricted feeding levels of ≃ 80% and 60% of the ad libitum level. The experiment was performed in 30 aquaria, each stocked with 12 fish. For each treatment (two diets x three feeding levels), there were five replicates. Fish were fed three times daily at 0900, 1300 and 1700 h. At sampling days (days 14, 29, 44) in each aquarium in one of these feedings, chromic-oxide-marked feed was used. Shortly after the last meal, fish were weighed and four fish were taken from each aquarium for determination of the chromic oxide content in their digestive tract. Fish fed the fish meal diet attained a higher weight but had a lower body protein content. At the ad libitum feeding level, feed intake of the fish meal diet was higher, but feed and protein utilization efficiency were lower than with the soya diet. However, statistical analysis of the data of both the ad libitum and the two restricted feeding levels revealed that the reduced voluntary feed intake of the soya diet was the cause of its better utilization with ad libitum feeding. There is no evidence that soya protein is more freely available than fish meal protein. The chromic oxide data showed that 15 min after feeding, all of the feed (99.8%) could be traced back in fish fed the lowest feeding level, while at the ad libitum feeding level the recovery was only 72%. These data confirmed the hypothesis that at high feeding levels, considerable amounts of feed remain uneaten. Feed losses were not significantly different between the two diets. The chromic oxide recovery data of the 0900 h and 1300 h feedings showed that the feed passage rate in the digestive tract was similar for the three different feeding levels. Due to the high feed losses at high feeding levels, the relation between feed ration and feed utilization is determined mainly by the percentage of feed losses at the different feed rations. Los juveniles de Colossoma macropomum (Cuvier) de 1 g se alimentaron con dos dietas diferentes: una con harina de pescado y otra con harina de soja como principal fuente de proteína dietética. Ambas dietas se proporcionaron con un nivel de alimentación ad libitum y con dos niveles de alimentación restringidos de ≃ 80 % y 60 % del nivel ad libitum. El experimento se realizó en 30 acuarios, cada uno con 12 peces. Para cada tratamiento (dos dietas x tres niveles de alimentación), hubo cinco repeticiones. Los peces fueron alimentados tres veces al día a las 0900, 1300 y 1700 h. En los días de muestreo (días 14, 29, 44) en cada acuario en una de estas alimentaciones, se utilizó alimento marcado con óxido de cromo. Poco después de la última comida, se pesaron los peces y se tomaron cuatro peces de cada acuario para determinar el contenido de óxido de cromo en su tracto digestivo. Los peces alimentados con la dieta de harina de pescado alcanzaron un mayor peso pero tenían un menor contenido de proteína corporal. En el nivel de alimentación ad libitum, el consumo de alimento de la dieta de harina de pescado fue mayor, pero la eficiencia de utilización del alimento y la proteína fue menor que con la dieta de soya. Sin embargo, el análisis estadístico de los datos tanto del nivel de alimentación ad libitum como de los dos niveles de alimentación restringida reveló que la reducción del consumo voluntario de alimento de la dieta de soja fue la causa de su mejor utilización con la alimentación ad libitum. No hay evidencia de que la proteína de soya esté más disponible que la proteína de harina de pescado. Los datos de óxido de cromo mostraron que 15 minutos después de la alimentación, todo el alimento (99,8 %) se pudo rastrear en los peces alimentados con el nivel de alimentación más bajo, mientras que en el nivel de alimentación ad libitum la recuperación fue solo del 72 %. Estos datos confirmaron la hipótesis de que a altos niveles de alimentación, quedan cantidades considerables de alimento sin comer. Las pérdidas de alimento no fueron significativamente diferentes entre las dos dietas. Los datos de recuperación de óxido de cromo de las alimentaciones de las 09:00 h y las 13:00 h mostraron que la tasa de paso del alimento en el tracto digestivo fue similar para los tres niveles de alimentación diferentes. Debido a las altas pérdidas de alimento a altos niveles de alimentación, la relación entre la ración de alimento y la utilización del alimento está determinada principalmente por el porcentaje de pérdidas de alimento en las diferentes raciones de alimento. Universidad Nacional, Costa Rica Escuela de Ciencias Biológicas

Salym Petroleum Development N.V. (SPD) is a 50/50 Joint Venture of Shell and Gazpromneft. SPD is the License holder and operator of the Salym Group of fields in Western Siberia (Upper Salym, West Salym and Vadelyp Work on maturation of Enhanced Oil Recovery option for Salym Petroleum Development (SPD) has began in 2007 and after initial screening, the ASP (Alkaline-Surfactant-Polymer) technology has been chosen for further work. Follow-up work involved laboratory and field tests, subsurface modelling and surface high-level concept design. High-level assessment demonstrated production potential of 30 mln tones additional oil and a significant potential value to be shared between SPD and Russian Government. At that stage work began on Production Pilot as a Separate Project with Pilot Concept selected and Front-End Engineering work completed in 2012.Construction and opperation is expected in 2013-2014. The chosen concept for the Pilot involves a single 100x100m square pattern with 4 injectors and one producer. Since the primary objective of the Pilot is to demonstrate technology and to collect data for further optimization, 2 additional observation wells will be drilled within the pattern to provide information about the effectiveness of the process. Wells will be drilled from a dedicated well pad in the Northern area of West Salym field. The same location will host standalone mixing and production facilities. Produced fluids will be collected in the tank farm at the well pad and analysed. Logistics and planning for assurance of quality control of chemical mix has provided a separate challenge, also exacerbated by remoteness of location, but also by rheology properties of viscous surfactnat concentrates. In addition all storage and mixing facilities have to survive harsh Siberian conditions with temperatures ranging from -50 to 40 deg C. The paper describes some subsurface, chemical and engineering solutions for Salym pilot that might be of value for other groups contemplating cEOR pilots and small-scale production in a similar area

Not only plantar pressure but also weight-bearing activity affects accumulated mechanical stress to the foot and may be related to foot ulceration. To date, activity has not been accounted for in leprosy. The purpose was to compare barefoot pressure, in-shoe pressure and daily cumulative stress between persons affected by leprosy with and without previous or current foot ulceration. Nine persons with current plantar ulceration were compared to 15 with previous and 15 without previous ulceration. Barefoot peak pressure (EMED-X), in-shoe peak pressure (Pedar-X) and daily cumulative stress (in-shoe forefoot pressure time integral×mean daily strides (Stepwatch™ Activity Monitor)) were measured. Barefoot peak pressure was increased in persons with current and previous compared to no previous foot ulceration (mean±SD=888±222 and 763±335 vs 465±262kPa, p

Objectives To evaluate the efficacy of treatment of plaque-type psoriasis with a moderate and a strong corticosteroid under continuous hydrocolloid occlusion, with weekly change of dressing, compared with treatment with the same corticosteroids alone, and the acceptance by the patients of his type of treatment. Setting Dermatological Departments of two University Hospitals and four General Hospitals. Design Open parallel study divided in two parts depending on the two different corticosteroid preparations applied. Each part was an intrasubject half-side study with left-right comparison. Subjects Fifty five patients with symmetrical, stable psoriasis plaques on elbows or knees. Methods Twenty nine patients were treated with clobetason butyrate cream (Emovate R ) twice daily as well as once weekly covered with a hydrocolloid dressing (Contreet R ) for four weeks. Twenty six patients were treated with clobetasol propionate cream (Dermovate R ) twice daily as well as once weekly covered by the hydrocolloid dressing for 2 weeks. Induration, erythema and scaling were assessed using a four-point scale. Plaque size was measured by multiplying the largest and the smallest diameter. Healing was defined as score 0 for scaling and induration and score 0 or 1 for erythema. Acceptance was evaluated by questions related to the wearing of the dressings: comfort of wearing, pain, itching, adhesiveness and sticking to clothing, and the performance of daily activities. Statistics analysis Sign test for the score values, parametric paired Student t -test for plaque size, chi-square test for healing. Results With occlusion a statistically significant increased reduction of severity was obtained compared to treatment without occlusion; this effect was more pronounced with the application of the strong corticosteroid. The questions related to the wearing of the dressing were answered positively by the majority of the patients. Conclusions Treatment of psoriasis plaques with, especially strong, corticosteroid creams under occlusion with a hydrocolloid dressing with a high adherence is rapid and effective. The acceptance of this type of treatment by the patients is high, and it permits normal daily activities.

Background Increased production of chemokines by adipose tissue and defective adipose tissue oxygenation as a result of obesity may induce leucocyte infiltration and subsequent systemic inflammation. Objectives 1-To determine the relation between the amount of visceral and subcutaneous adipose tissue and the chemokine interferon-γ-inducible protein 10 (IP-10) and angiogenic factor hepatocyte growth factor (HGF). 2-To determine the relation between the metabolic syndrome and IP-10 as well as HGF. Methods Patients originated from the Secondary Manifestations of ARTerial disease (SMART) cohort. In this study, a cohort of 1251 patients with manifest vascular disease was included. Subcutaneous and visceral adipose tissue thickness (SAT and VAT respectively) were measured ultrasonographically. IP-10 and HGF concentrations were measured with Luminex multiplex immuno assay in addition to fasting metabolic parameters. Linear regression analyses with adjustments for age, gender, smoking, estimated glomerular filtration rate, type 2 diabetes mellitus and medication use were applied to quantify the relations between adiposity or metabolic syndrome and IP-10 and HGF concentrations. Results VAT was significantly associated with (log)IP-10 and (log)HGF, reflected by significant higher β-values in VAT quartile 4 compared with VAT quartile 1 (reference): β0.155 (95%CI:0.073–0.237) for IP-10 and β0.147 (95%CI:0.076–0.218) for HGF. Per standard deviation increase in VAT, (log)IP-10 levels increased with 0.057 pg/mL (95%CI:0.027–0.087) and (log)HGF increased with 0.051 pg/mL (95%CI:0.025–0.077). Effect estimates were not affected by including body mass index(BMI) in the model. In contrast, SAT was not associated with IP-10 and HGF. Furthermore, the presence of the metabolic syndrome was associated with IP-10 and HGF. Conclusions Visceral adipose tissue but not subcutaneous adipose tissue is significantly associated with circulating levels of IP-10 and HGF, irrespective of BMI.

We present a 37-year-old woman with an 8-year history of rosacea, who developed persistent swelling of the right lower eyelid, diagnosed as Morbihan's disease. Morbihan's disease is considered a rare complication of rosacea.

Molenschwangerschaften mit koexistentem, lebendem Fetus sind extrem selten. Haufig liegt eine Zwillingsgraviditat mit sonographisch getrennten Schwangerschaften vor. Berichtet wird der Fall einer Einzelplazenta mit dem gleichzeitigen Vorliegen einer fokal in der Plazenta liegenden kompletten Blasenmole und einer komplexen Fehldifferenzierung des Restparenchyms. Diese Plazentaveranderungen haben zu einer intrauterinen Wachstumsretardierung des Feten gefuhrt, der in der 34. SSW hypotroph geboren wurde. Eine persistierende Trophoblasterkrankung entwickelte sich post natum nicht. Die Moglichkeiten der Entstehung von Schwangerschaften mit dem Nebeneinander von moligen Plazentaveranderungen und lebendem Kind und deren Bedeutung werden diskutiert.

Matrix acid treatment design in clastic formations has traditionally been based on field experience or core-flushing tests. The choice of stimulation fluid compositions has frequently been limited to full-strength (12% HCl/3% HF) or half-strength (6% HCl 1.5% HF) mud acid. These practical rules of thumb have given good results but have not always ensured an optimum acid/rock reaction, i.e. the maximum net dissolution of the rock minerals and impairment coupled with a minimum of secondary precipitate formation. This paper shows how mathematical modelling of the chemical equilibria using a thermodynamic simulator can identify the ideal acid formulation, even when cores are not available. The input for the simulator is the mineralogical composition of the formation (from cuttings, sidewall samples or cores), the nature of the inorganic damage and the rock's porosity-permeability relationship. Chemical equilibria are calculated for different acid compositions taking into account the dynamic nature of the acidising process: the drop in acid strength during reaction with the damaged formation, and the changing rock composition due to attack by the acid. The results are translated via the porosity-permeability relationships into a theoretical well-productivity improvement factor. The acid composition which gives the highest productivity improvement is the optimum or Specially Formulated Mud Acid (SFMA) composition. It is important to note that the SFMA concept is not limited to HCl or HCl/HF acid formulations, but can also deal with other types such as Buffer Regulated HydroFluoric Acid (BRHFA). It will be shown that different rock compositions lead to very different SFMA formulations. SFMA recipes have been tested in core-flushing experiments, and have been found to give better performance than standard mud-acid recipes. The procedure was further validated by analysing the spent fluids regained by back production after field treatment. Field case histories in which improved production results were achieved using the SFMA approach are described.

Adipose tissue dysfunction is associated with inflammation, type 2 diabetes mellitus and vascular diseases. Visceral adipose tissue (VAT)-derived adipokines, which are released in the portal circulation may influence liver metabolism. (1) To estimate the contribution of VAT and subcutaneous adipose tissue (SAT) on adipokine levels by measuring differences in adipokine concentrations between the portal draining inferior mesenteric vein and the subclavian vein. (2) To determine the relation of both VAT and SAT quantity and composition to mesenteric and systemic concentrations of adipokines. Cross-sectional cohort study. A total of 32 patients undergoing abdominal aortic surgery. A panel of 18 adipokines was measured in perioperatively obtained blood samples from the subclavian vein and the inferior mesenteric vein. Adipocyte size, macrophage infiltration and capillary density were measured in subcutaneous and mesenteric adipose tissue biopsies; SAT and VAT areas were measured on computed tomography images. Serum interferon-γ-inducible protein 10 (IP-10) and hepatocyte growth factor (HGF) concentrations were significantly higher in the inferior mesenteric vein vs the subclavian vein. SAT area (β –18; 95% confidence interval (CI) −35 to −2), subcutaneous adipocyte size (β –488; 95% CI −938 to −38) and SAT macrophages quantity (β –1439; 95% CI −2387 to −491) were negatively associated with adiponectin levels in the systemic circulation. SAT area was related to systemic concentrations of leptin. Mesenteric adiponectin concentrations were related to VAT area (β –20; 95% CI −35 to −5) and visceral adipocyte size (β −1076; 95% CI −1624 to −527). VAT area, adipocyte size and capillary density were related to systemic adiponectin concentrations. SAT and VAT quantities as well as morphologic characteristics of both adipose tissue depots are related to systemic and mesenteric adipokine concentrations. There were no differences in adipokine concentrations between the mesenteric and subclavian vein, except for higher IP-10 and HGF concentrations in the inferior mesenteric vein, indicating a possible contribution of VAT to IP-10 and HGF levels.

Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincare plot analysis (PPA), the segmented Poincare plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed significant differences (p < 0.001) also of the systolic blood pressure. Further on, linear discrimination analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders.

A 26-year-old white woman came to the clinic because of white spots. The spots were confluent in the midline, non-scaly and localized on trunk and proximal parts of the arms. Biopsy showed loss of pigment in the epidermis. The diagnosis was: progressive macular hypomelanosis.

A different clinical picture and therapeutic response were observed when data from Leishmania major-infected Dutch military personnel stationed in southern (N = 8) and northern (N = 169) Afghanistan were analyzed. Clinical presentation of cutaneous leishmaniasis in personnel in the south was milder and seemed to respond better to antileishmanial treatment; molecular analyses of parasite isolates seem to indicate that these differences may be genetic.

Aims: To investigate whether levels of thyroid-stimulating hormone (TSH) within the normal range are associated with an increased risk of new vascular events and mortality in patients with clinical manifest vascular diseases and whether this relation is influenced by adiposity. Methods and results: Prospective cohort study in 2443 patients (1790 men and 653 women) with clinical manifest vascular disease and TSH levels in the normal range. Median follow up was 2.7 (interquartile range 1.4–3.9) years. Clinical endpoints of interest were: myocardial infarction, stroke, vascular death, and all-cause mortality. In patients with manifest vascular disease, the prevalence of (subclinical) hypothyroidism was 5.7%, while 3.6% had (subclinical) hyperthyroidism. An increase in 1 unit of TSH was associated with a 33% higher risk (HR 1.33; 95% CI 1.03–1.73) for the occurrence of myocardial infarction, adjusted for age, gender, renal function, and smoking. In patients with a body mass index (BMI) below the median of 26.7 kg/m2 the HR per unit TSH for myocardial infarction was 1.55 (95% CI 1.08–2.21) compared to 1.18 (95% CI 0.81–1.71) in patients with a BMI ≥26.7 kg/m2. Visceral adipose tissue thickness below the median (≤8.8 cm) was associated with higher HR per unit TSH for myocardial infarction (HR 1.69; 95% CI 1.21–2.35) compared to visceral adipose tissue thickness >8.9 cm (HR 1.00; 95% CI 0.66–1.49). There was no relation between TSH and risk of stroke, vascular death, the combined endpoint, or all-cause mortality. Conclusion: Higher TSH levels within the normal range are associated with an increased risk of myocardial infarction, in patients with clinical manifest vascular disease. This relation is most prominent in patients without visceral obesity.

An increasing demand on load flexibility in power supply networks is the motivation to look at flexible, and possibly optimal control systems for power plants with carbon capture units. Minimizing the energy demand for carbon dioxide removal under these circumstances reduces the cost disadvantage of carbon capture compared to conventional production. In this work a dynamic model in Modelica of a chemical absorption process run with an aqueous monoethanolamine (MEA) is developed, and used for solving optimal control problems. Starting from a rather detailed dynamic model of the process, model reduction is performed based on physical insight. The reduced model computes distinctly faster, shows similar transient behavior and reflects trends for optimal steady-state operations reported in the literature. The detailed model has been developed in Dymola, and the reduced model is used in JModelica.org, a platform supporting non-linear dynamic optimization. First results are shown on the dynamic optimization of the desorption column, the main cause of energy usage in the process. (Less)

Summary Skin lesions occur frequently in travelers to tropical countries. Military personnel acquire skin lesions regularly during jungle training as did Dutch troops who trained in the jungle of Belize in 1998, 2004 and 2009, in an area endemic for cutaneous leishmaniasis. Demographic and clinical data were collected retrospectively. Diagnostic investigations for cutaneous leishmaniasis included Giemsa stain, culture, PCR and NASBA and histopathology of biopsies. Treatment of leishmaniasis was with sodium stibogluconate, given intravenously or intralesionally, the latter with cryotherapy. In 1998 and 2004 cutaneous leishmaniasis due to Leishmania braziliensis and Leishmania mexicana infection was diagnosed in 25 persons out of 99 (attack rate 25.2%) and 14 persons out of 80 (attack rate 17.5%) respectively. In 2009 cutaneous leishmaniasis was not acquired. Skin problems were common during and after jungle training. Cutaneous leishmaniasis was important in the first two cohorts but not observed in the third cohort. Factors that could have played a role in the absence of cutaneous leishmaniasis in the third cohort include variability in transmission and availability of better preventive measures and adherence to these. Sodium stibogluconate treatment, intralesional or intravenous, was effective.

Cutaneous leishmaniasis caused by Leishmania major infection affected 172 (18.3%) of 938 Dutch military troops deployed in northern Afghanistan in 2005. The high attack rate was a result of initial insufficient availability of means of prevention and insufficient adherence to preventive measures. At presentation, the lymphatic system was involved in 24.8%. Treatment with intralesional injections of antimony with or without cryotherapy was satisfactory, but 19.5% of patients received secondary treatment with miltefosine. Six months after treatment, 128 (77.1%) of 166 treated patients were cured, 16 (9.6%) were lost to follow-up, and 22 (13.3%) already experienced cure at six weeks but were not seen at six months. Natural evolution played a role in this observational study, which showed cure of all patients seen at six months. In general, management of cutaneous leishmaniasis was feasible under field conditions.

Objective: To explore the relationships between perceived limitations in walking-related daily activities, walking ability (capacity), and the amount of daily walking (performance) in persons affected by leprosy and to identify their determinants. Design: A cross-sectional study. Subjects: Thirty-nine persons affected by leprosy. Methods: Perceived limitations were assessed with the World Health Organization Disability Schedule 11, domain "getting around". Walking capacity was assessed as covered distance in 6 min. Walking performance was recorded as mean strides/day with the Stepwatch(TM) 3 Activity Monitor. Potential determinants were sensory function, foot deformities, joint mobility, ankle muscle strength and co-morbidity. Results: Perceived limitations in walking-related activities were significantly correlated with walking capacity (r=-0.47; p < 0.01) but not with walking performance, although walking capacity significantly correlated with walking performance (r=0.38; p < 0.05). Various foot impairments independently contributed to reduced walking capacity and, to a lower degree, to perceived limitations in activities and performance. Conclusion: People affected by leprosy perceive limitations in walking-related activities that are determined by a reduced walking ability and the severity of foot impairments. Since perceived limitations in walking-related activities were not related to walking performance, perceived limitations are apparently weighted against the individual's needs

Background: Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) affecting a large number of patients. Because of its potential debilitating effects, identification of patients at high risk for the development of this syndrome is relevant, and only a few predictors are known. Objectives: To assess the incidence and potential predictors of PTS. Methods: We prospectively followed 111 consecutive patients for 2 years after a first episode of objectively documented DVT of the leg. With non-invasive venous examinations, residual thrombosis, valvular reflux, calf muscle pump function and venous outflow resistance were assessed at 6 weeks, 3 months, 6 months, 1 year, and 2 years. The Clinical, Etiologic, Anatomic, and Pathophysiologi classification was used to record the occurrence and severity of PTS. Regression analysis with area under the receiver operating characteristic (ROC) curve was performed to identify potential predictors. Results: The cumulative incidence of PTS was 46% after 3 months, and the incidence and severity did not increase further. Men appeared to be at increased risk as compared with women (risk ratio [RR] 1.4, 95% confidence interval [CI] 0.9-2.2), as were patients over 50 years as compared with younger patients (RR 1.4%, 95% CI 0.9-2.1). Patients with thrombosis localized in the proximal veins at diagnosis had an increased risk of PTS as compared with patients with distal thrombosis (RR 2.3%, 95% CI 1.0-5.6). PTS developed in 32 of 52 patients (62%) with residual thrombosis in the proximal veins 6 weeks after diagnosis, as compared with 17 of 45 patients (38%) without residual proximal thrombosis, leading to a 1.6-fold increased risk (95% CI 1.0-2.5). The presence of valvular reflux in the superficial veins was also a predictor at 6 weeks, with a 1.6-fold increased risk as compared with patients without superficial reflux (95% CI 1.1-2.3). A multivariate analysis of these predictors yielded an area under the ROC curve of 0.72 (95% CI 0.62-0.82). Conclusions: PTS develops in half of all patients within 3 months, with no further increase being seen up to 2 years of follow-up. Male sex, age over 50 years, proximal localization of the thrombus at entry, residual proximal thrombosis and superficial valvular reflux at 6 weeks seem to be the most important predictors of PTS in patients with a first episode of DVT. Duplex scanning 6 weeks after diagnosis appears to be clinically useful for the identification of patients at risk of PTS.

Although foot pressure has been reported to be increased in people affected by leprosy, studies on foot pressure and its determinants are limited. Therefore, the aim was to assess barefoot plantar foot pressure and to identify clinical determinants of increased plantar foot pressure in leprosy affected persons. Plantar pressure in both feet was assessed using the Novel EMED-X platform in 39 persons affected by leprosy. Peak pressure was determined for the total foot and four regions: hallux, metatarsal heads, midfoot and heel. Potential determinants were: age, weight, nerve function (Neuropathy Disability Score, Pressure Perception Threshold and Vibration Perception Threshold), toe and foot deformities, joint mobility, ankle muscle strength and callus. Increased peak pressure (>600 kPa) was observed in 46% of the participants. The highest peak pressure (mean) was found in the metatarsal heads region (right 549 (SD 321) kPa; left 530 (SD 298) kPa). Multilevel regression analysis showed that Neuropathy Disability Score, amputation/absorption of toes and hallux valgus independently contributed to metatarsal heads peak pressure in persons affected with leprosy. To conclude, peak pressure is increased in people affected by leprosy. The highest peak pressure is found in the forefoot region and is significantly associated to Neuropathy Disability Score, toe amputation/absorption and hallux valgus. Screening for clinical characteristics can be used to identify individual persons affected by leprosy at risk of excessive pressure. (C) 2011 Elsevier B.V. All rights reserved

A purification scheme for cell culture-derived smallpox vaccines based on an orthogonal downstream process of pseudo-affinity membrane adsorbers (MA) and hydrophobic interaction chromatography (HIC) was investigated. The applied pseudo-affinity chromatography, based on reinforced sulfated cellulose and heparin-MA, was optimized in terms of dynamic binding capacities, virus yield and process productivity. HIC was introduced as a subsequent method to further reduce the DNA content. Therefore, two screens were undertaken. First, several HIC ligands were screened for different adsorption behavior between virus particles and DNA. Second, elution from pseudo-affinity MA and adsorption of virus particles onto the hydrophobic interaction matrix was explored by a series of buffers using different ammonium sulfate concentrations. Eventually, variations between different cultivation batches and buffer conditions were investigated.The most promising combination, a sulfated cellulose membrane adsorber with subsequent phenyl HIC resulted in overall virus particle recoveries ranging from 76% to 55% depending on the product batch and applied conditions. On average, 61% of the recovered virus particles were infective within all tested purification schemes and conditions. Final DNA content varied from 0.01% to 2.5% of the starting material and the level of contaminating protein was below 0.1%.

Conventional techniques, such as plain radiography and bone-scintigraphy, were used in the past to evaluate skeletal changes in patients with leprosy. More recent publications focus on radiological imaging of affected nerves, and involve advanced modalities such as Computed Tomography (CT-scan), Ultrasonography (US), and Magnetic Resonance Imaging (MRI). US and MRI can play an especially important role in the evaluation of nerve involvement in newly diagnosed patients, and also during leprosy reactions. This is important, because when nerve involvement is diagnosed in time, it may be reversible with adequate treatment. Radiological modalities can also play an important role during the followup of patients with leprosy with nerve function impairment. Skeletal and soft-tissue abnormalities occur, even after treatment. The so-called neuropathic foot is a well known consequence. Because of nerve function impairment, there is a constant risk of developing ulcers and subsequent osteomyelitis, or neuro-osteoarthropathy (Charcot foot or tarsal disintegration), which can lead to the amputation of the affected limb. Different radiological modalities can be used during the evaluation and follow-up of patients with leprosy with a neuropathic foot. With this up-to-date review, we highlight the importance and potential role of radiological imaging techniques in leprosy.

Proteins of the antigen 85 complex in the 30-kDa region secreted by live mycobacteria are important in the immune response against mycobacterial infections and may play an important biological role in the host-parasite interaction. In the present study, we have characterized epitopes of the 30-kDa-region proteins and the antigen 85 complex by using a panel of 13 monoclonal antibodies (MAbs) reacting with these antigens, 6 of which have not been described before. By using five previously characterized related secreted proteins of Mycobacterium tuberculosis, MPT44 (85A), MPT59 (85B), MPT45 (85C), MPT51 (27 kDa), and MPT64 (26 kDa), we have identified at least 10 different MAb-reactive epitopes on the proteins of the antigen 85 complex. A heterogeneous distribution of epitopes was observed within the components of the antigen 85 complex. Two distinct epitopes specific for antigen 85B and two other epitopes restricted to the 85A and 85B components were recognized. Two of them were shared with a previously unidentified 27-kDa protein present in M. tuberculosis culture fluid from which all MPT proteins were derived. The rest of the MAb-reactive epitopes were found to be present mostly in antigens 85A and 85B and to a lesser extent in antigen 85C. None of these MAbs recognized component 85C alone nor did they bind to the related MPT51 and MPT64 proteins. Interestingly, most of the MAbs reacted with purified native proteins of the antigen 85 complex but not to them in their denatured forms. In contrast, reactivity of the MAbs with the cytosol fraction of M. tuberculosis in immunoblotting revealed that they bound to a closely related cytosolic 30-kDa protein(s) even when they were denatured. Heterogeneity of these MAb-reactive epitopes of the antigen 85 complex was further evident as they were found to be distributed in various patterns among 19 different mycobacterial species. By using fusion proteins of the Mycobacterium leprae 30/31-kDa antigen 85 complex, we have localized at least six different epitopes within amino acid residues 55 to 266 of the M. leprae antigen 85 complex. Finally, by immunohistochemical analysis, we have demonstrated the in situ expression of one of the novel MAb-reactive epitopes specific for antigen 85B on the cell wall surface of M. leprae within macrophages in lepromatous leprosy lesions and thus provide direct evidence for the presence of the B component of the antigen 85 complex on the surface of intact M. leprae.

Buruli ulcers have not been previously described in China, and only once at higher latitudes on the northern hemisphere. A patient who travelled in the Shan Dong Province in the People's Republic of China developed an ulcer which was proven to be a Buruli ulcer. The clinical picture and histopathological findings from biopsy specimens are characteristic for a Buruli ulcer, and also the growth in culture (Coletsos medium) at a restricted temperature of 30 degrees C. A multiplex polymerase chain reaction (PCR) based on the amplification of the gene encoding for 16S ribosomal RNA and a nested PCR based on the Mycobacterium ulcerans specific repeated sequence 2404 were performed. These PCR investigations identified the bacteria as M. ulcerans, subspecies shinshuense. The patient was initially treated with clarithromycin and rifampicin, which was changed to ciprofloxacin and rifabutin when rifampicin resistance of the first isolate was established. There were no signs of reactivation of the disease 6 months after the end of treatment. M. ulcerans infection occurs above 30 degrees latitude on the northern hemisphere in China and is caused by M. ulcerans, subspecies shinshuense. This case appears to be cured by chemotherapy alone, in contrast to the general experience that surgical treatment is indicated. The granulomatous reaction with only fragments of acid-fast bacteria in the biopsy at the end of treatment many indicate the development of an adequate cell-mediated immune response leading to resistance to the infection.

Background Obesity is related to the development of vascular diseases and metabolic complications. Low grade inflammation is a key feature of central obesity, characterized by elevated plasma levels of C-reactive protein (CRP). We hypothesize that visceral adipose tissue contributes to systemic concentrations of CRP. Methods In 2410 patients (1729 men and 681 women) with vascular diseases, subcutaneous and visceral fat masses were analyzed with ultrasonography. Metabolic parameters and CRP were measured in a fasting state. The association between fat measurements and plasma CRP was quantified using linear regression analysis. CRP levels were logarithmically transformed. Adjustments were made for age, smoking, type 2 diabetes mellitus, insulin resistance (HOMA-IR) and medication use. Results Visceral fat was categorized into quartiles ( Q ) ranging from 3.2 to 7.8cm in Q1 (reference) to 11.0–19.8cm in Q4 in men and 2.7–6.0cm in Q1 (reference) to 9.0–17.4cm in Q4 in women. β -coefficients gradually increased across the quartiles from 0.07 (0.01–0.13) in Q2 to 0.25 (0.19–0.31) in Q4 in men and 0.17 (0.07–0.26) in Q2 to 0.42 (0.32–0.52) in Q4 in women, indicating 0.25 and 0.42mg/l higher logarithmically transformed (log)CRP levels in Q4 compared to Q1 in respectively men and women. Per standard deviation increase of visceral fat, logCRP levels increased with 0.10mg/l (0.07–0.12) in men and with 0.11 (0.15–0.19) in women. Likewise, in separate analyses waist circumference and body mass index showed a positive, but weaker association with logCRP levels across quartiles (in men: β 0.21 (0.15–0.27) in Q4 for waist circumference and β 0.23 (0.17–0.30) in Q4 for body mass index; in women: β 0.32 (0.22–0.42) in Q4 for waist circumference and β 0.32 (0.22–0.42) in Q4 for body mass index). In men subcutaneous fat was not associated with logCRP ( β -coefficients relative to Q1: −0.01 (−0.07 to −0.05), −0.01 (−0.07 to −0.05) and 0.05 (−0.01 to −0.11) in Q2 to Q4 respectively). Conclusions In conclusion, visceral fat thickness is the strongest contributor to the systemic CRP concentrations in patients with vascular diseases.

Rheumatoid arthritis was diagnosed in a 65-year-old man from Suriname, on the basis of clinical and radiological findings. However, he was eventually diagnosed with leprosy. This emerged when the patient developed skin lesions and complained of increasing sensibility disorders during treatment for the alleged rheumatoid arthritis. He was treated with a combination therapy consisting of rifampicin, clofazimine, dapsone, and prednisone. The skin lesions and joint symptoms were resolved as a result of this, but the sensibility disorders persisted. As physicians are not sufficiently familiar with leprosy and the condition has many manifestations that can mimic more frequently occurring diseases, leprosy is often diagnosed at a later stage. This may result in irreversible damage, especially to the peripheral nerves, which may lead to disability. Therefore, for patients who originate from areas where leprosy is endemic and who suffer from joint complaints in combination with skin or sensibility disorders, the diagnosis of leprosy should be considered.

Leprosy control programs would benefit expressively from an easy method to estimate disease prevalence and to assess the effect of leprosy control measures on disease prevalence. Determination of the seroprevalence of antibodies to PGL-I through school children surveys might be a useful indicator of leprosy prevalence at the district level. To investigate whether seropositivity rates could be related to leprosy detection rates and whether seropositivity could be used as a proximal indicator to predict the leprosy incidence in other areas, 7,073 school children in three different leprosy-endemic states in Brazil were tested. The results show a widely varying distribution of seropositivity in the communities independent of the number of leprosy cases detected. Seroprevalence was significantly lower at private schools. No differences in the patterns of seropositivity between ELISA and dipstick were observed. No correlation between leprosy detection rate and seropositivity rates could be established.

Obesity is associated with an increased incidence of insulin resistance (IR), type 2 diabetes mellitus and cardiovascular diseases. The increased risk for cardiovascular diseases could partly be caused by a prothrombotic state that exists because of abdominal obesity. Adipose tissue induces thrombocyte activation by the production of adipose tissue-derived hormones, often called adipokines, of which some such as leptin and adiponectin have been shown to directly interfere with platelet function. Increased adipose tissue mass induces IR and systemic low-grade inflammation, also affecting platelet function. It has been demonstrated that adipose tissue directly impairs fibrinolysis by the production of plasminogen activator inhibitor-1 and possibly thrombin-activatable fibrinolysis inhibitor. Adipose tissue may contribute to enhanced coagulation by direct tissue factor production, but hypercoagulability is likely to be primarily caused by affecting hepatic synthesis of the coagulation factors fibrinogen, factor VII, factor VIII and tissue factor, by releasing free fatty acids and pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-1beta and interleukin-6) into the portal circulation and by inducing hepatic IR. Adipose tissue dysfunction could thus play a causal role in the prothrombotic state observed in obesity, by directly and indirectly affecting haemostasis, coagulation and fibrinolysis.

We investigated the association between a polymorphism of a key innate immunity receptor, Toll-like receptor 1 (TLR1) N248S, and susceptibility to leprosy and its clinical presentation. TLR1 N248S has been shown elsewhere to diminish TLR1 signaling and subsequent leprosy disease. The homozygous genotype SS was more frequent (P = .012) and the heterozygous SN genotype was less frequent (P = .015) in patients with leprosy than in control subjects. Additional observed differences in allelic frequency in patients who experienced reversal reactions and/or erythema nodosum leprosum reactions indicates that altered TLR1 function, or at least a TLR1 N248S-linked trait, may affect the progression from infection to disease as well as the disease course and the risk of debilitating reactional episodes in this population.

A magnetic resonance imaging (MRI) protocol was performed in leprosy patients with a neuropathic foot and superficial ulcers and/or localized cellulitis but no clinical suspicion of osteomyelitis. The aim of the study was to determine if unsuspected osteomyelitis was present in this defined group of leprosy patients. A total of 15 neuropathic feet from 9 patients were included. Clinically and on MRI, the forefoot was predominantly affected. MRI findings of osteomyelitis were found in 4 feet. In feet with osteomyelitis, 3 had a superficial ulcer and 3 had clinical signs of localized cellulitis. A clinical diagnosis of cellulitis was confirmed on MRI in 2 feet.A striking discrepancy between clinical and MRI findings was found.This study shows that, compared with clinical evaluation, MRI is a sensitive method for the detection of unsuspected osteomyelitis in neuropathic feet with superficial ulcers and/or cellulitis. MRI findings in this group of patients may influence clinical decision making and may prevent further complications, because osteomyelitis requires more aggressive medical treatment. This preliminary communication should pave the wave for designed controlled studies so that patients with Hansen’s neuropathy may get the best medical care.

Smallpox is an acute, highly infectious viral disease unique to humans, and responsible for an estimated 300-500 million deaths in the 20th century. Following successful vaccination campaigns through the 19th and 20th centuries, smallpox was declared eradicated by the World Health Organization in 1980. However, the threat of using smallpox as a biological weapon prompted efforts of some governments to produce smallpox vaccines for emergency preparedness. An additional aspect for the interest in smallpox virus is its potential use as a platform technology for vector vaccines. In particular, the latter requires a high safety level for routine applications. IMVAMUNE, a third generation smallpox vaccine based on the attenuated Modified Vaccinia Ankara (MVA) virus, demonstrates superior safety compared to earlier generations and represents therefore an interesting choice as viral vector. Current downstream production processes of Vaccinia virus and MVA are mainly based on labor-intensive centrifugation and filtration methods, requiring expensive nuclease treatment in order to achieve sufficient low host-cell DNA levels for human vaccines. This study compares different ion exchange and pseudo-affinity membrane adsorbers (MA) to capture chicken embryo fibroblast cell-derived MVA-BN after cell homogenization and clarification. In parallel, the overall performance of classical bead-based resin chromatography (Cellufine sulfate and Toyopearl AF-Heparin) was investigated. The two tested pseudo-affinity MA (i.e., sulfated cellulose and heparin) were superior over the applied ion exchange MA in terms of virus yield and contaminant depletion. Furthermore, studies confirmed an expected increase in productivity resulting from the increased volume throughput of MA compared to classical bead-based column chromatography methods. Overall virus recovery was approximately 60% for both pseudo-affinity MA and the Cellufine sulfate resin. Depletion of total protein ranged between 86% and 102% for all tested matrices. Remaining dsDNA in the product fraction varied between 24% and 7% for the pseudo-affinity chromatography materials. Cellufine sulfate and the reinforced sulfated cellulose MA achieved the lowest dsDNA product contamination. Finally, by a combination of pseudo-affinity with anion exchange MA a further reduction of host-cell DNA was achieved.

The polymerase chain reaction (PCR) based on the selective amplification of a 530-bp fragment of the gene encoding the proline-rich antigen of Mycobacterium leprae was applied on sections of fixed or frozen biopsy samples from leprosy patients. A simple procedure for the extraction of DNA from M. leprae in clinical specimens that provided suitable template DNA for amplification was developed. When PCR was applied on frozen sections, positive amplification in samples from all untreated acid-fast bacillus (AFB)-positive patients and in samples from 56% of the untreated AFB-negative patients could be detected, while biopsy samples from patients with skin diseases other than leprosy were all PCR negative. With neutral Formalin-fixed biopsy samples, positive amplification in 92% of the samples from untreated AFB-positive patients and in 61% of the samples from untreated AFB-negative patients could be detected by PCR. Biopsy samples exposed to mercuric chloride or nonbuffered formaldehyde containing fixatives were not suitable for application of PCR. This PCR holds promise as a tool for studies on M. leprae infection.

An MRI study done in 2000 on 10 leprosy patients with neuropathic feet, without clinical complications such as ulcerations, osteomyelitis or Charcot deformities revealed abnormalities in nine patients, with degradation, interruption of subcutaneous fat and effusion/synovitis, all located in the first metatarsophalangeal (MTP) region. Since these MRI abnormalities may precede clinical complications of the foot, a follow-up study was performed.A new evaluation was based on a clinical examination and an MRI of the same patients who participated in the initial study.Four patients were lost to follow-up. Average follow-up period was 4-6 years. MRI abnormalities in the MTP 1 region in the first study were no longer visible in three patients, but were still present in two patients. In six patients new MRI findings were found, without clinical evidence of ulceration, osteomyelitis or Charcot deformity. No relationship was found between MRI findings in the MTP 1 region at the start of the study and the development of foot ulcers, callus or skin fissures in the MTP 1 region during follow-up.MRI findings of interruption and infiltration of the subcutaneous fat in leprosy patients with uncomplicated neuropathic feet do not necessarily have any clinical implication for the development of future foot problems.

Cutaneous leishmaniasis (CL) is a widespread disease in Suriname caused by Leishmania Viannia guyanensis. It is argued that other Leishmania species are also responsible for CL and that the incidence is increasing. This study aimed to identify the species causing the disease and to estimate the annual detection rate of CL in Suriname in 2006. In Paramaribo, 152 patients were registered, of whom 33 were tested in two polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods. Twenty-seven patients were infected with L. (V.) guyanensis (complex), one with L. (V.) lainsoni, and one with L. (Leishmania) amazonensis. In the hinterland, 162 CL suspected patients were registered by questionnaires; of these, 24 of 27 tested positive by PCR-RFLP (88.9%; 95% CI, 77.1-100%). With extrapolation of collected data, a detection rate was calculated of 5.32 to 6.13 CL patients per 1,000 inhabitants for the hinterland and 0.64 to 0.74 patients per 1,000 inhabitants for the whole country.

Skin ulcers are a commonly encountered problem at departments of tropical dermatology in the Western world. Furthermore, the general dermatologist is likely to be consulted more often for imported chronic skin ulcers because of the ever-increasing travel to and from tropical countries. The most common cause of chronic ulceration throughout the world is probably pyoderma. However, in some parts of the world, cutaneous leishmaniasis is one of the most prevalent causes. Mycobacterium ulcerans is an important cause of chronic ulcers in West Africa. Bacterial infections include pyoderma, mycobacterial infections, diphtheria, and anthrax. Pyoderma is caused by Staphylococcus aureus and/or beta-hemolytic streptococci group A. This condition is a common cause of ulcerative skin lesions in tropical countries and is often encountered as a secondary infection in travelers. The diagnosis is often made on clinical grounds. Antibacterial treatment for pyoderma should preferably be based on culture outcome. Floxacillin is generally active against S. aureus and beta-hemolytic streptococci. Infection with Mycobacterium ulcerans, M. marinum, and M. tuberculosis may cause ulcers. Buruli ulcers, which are caused by M. ulcerans, are endemic in foci in West Africa and have been reported as an imported disease in the Western world. Treatment is generally surgical, although a combination of rifampin (rifampicin) and streptomycin may be effective in the early stage. M. marinum causes occasional ulcerating lesions in humans. Treatment regimens consist of combinations containing clarithromycin, rifampin, or ethambutol. Cutaneous tuberculosis is rare in travelers but may be encountered in immigrants from developing countries. Treatment is with multiple drug regimens consisting of isoniazid, ethambutol, pyrazinamide, and rifampin. Cutaneous diphtheria is still endemic in many tropical countries. Cutaneous diphtheria ulcers are nonspecific and erythromycin and penicillin are both effective antibacterials. Antitoxin should be administered intramuscularly in suspected cases. Anthrax is caused by spore-forming Bacillus anthracis. This infection is still endemic in many tropical countries. Eschar formation, which sloughs and leaves behind a shallow ulcer at the site of inoculation, characterizes cutaneous anthrax. Penicillin and doxycycline are effective antibacterials. Cutaneous leishmaniasis is caused by different species belonging to the genus Leishmania. The disorder is one of the ten most frequent causes of skin diseases in travelers returning from (sub)tropical countries. The clinical picture is diverse, ranging from a painless papule or nodule to an ulcer with or without a scab. Treatment depends on the clinical manifestations and the species involved.Sporotrichosis, chromo(blasto)mycosis, and mycetoma are the most common mycoses that may be accompanied by ulceration. Infections are restricted to certain regions and often result from direct penetration of the fungus into the skin. Anti-mycotic treatment depends on the microorganism involved. The most common causes of infectious skin ulceration encountered in patients from tropical countries who present at a department of tropical dermatology are reviewed in this article.