An exudate detection method for diagnosis risk of diabetic macular edema in retinal images using feature-based and supervised classification.

The present paper aims at presenting the methodology and first results of a detection system of risk of diabetic macular edema (DME) in fundus images. The system is based on the detection of retinal exudates (Ex), whose presence in the image is clinically used for an early diagnosis of the disease. To do so, the system applies digital image processing algorithms to the retinal image in order to obtain a set of candidate regions to be Ex, which are validated by means of feature extraction and supervised classification techniques. The diagnoses provided by the system on 1058 retinographies of 529 diabetic patients at risk of having DME show that the system can operate at a level of sensitivity comparable to that of ophthalmological specialists: it achieved 0.9000 sensitivity per patient against 0.7733, 0.9133 and 0.9000 of several specialists, where the false negatives were mild clinical cases of the disease. In addition, the level of specificity reached by the system was 0.6939, high enough to screen about 70% of the patients with no evidence of DME. These values show that the system fulfils the requirements for its possible integration into a complete diabetic retinopathy pre-screening tool for the automated management of patients within a screening programme. Graphical Abstract Diagnosis system of risk of diabetic macular edema (DME) based on exudate (Ex) detection in fundus images.

Copeptin and insulin resistance: effect modification by age and 11 ß-HSD2 activity in a population-based study.

PURPOSE: Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11ß-hydroxysteroid-dehydrogenase-type 2 (11ß-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11ß-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population. METHODS: This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18-90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11ß-HSD2 activity were presented as appropriate. RESULTS: Plasma copeptin was higher in men [median 5.2, IQR (3.7-7.8) pmol/L] than in women [median 3.0, IQR (2.2-4.3) pmol/L], P < 0.0001. HOMA-IR was positively associated with copeptin after full adjustment if 11ß-HSD2 activity was high [ß (95% CI) = 0.32 (0.17-0.46), P < 0.001] or if age was high [ß (95% CI) = 0.34 (0.20-0.48), P < 0.001], but not if either 11ß-HSD2 activity or age was low. There was a positive association of type 2 diabetes with copeptin [OR (95% CI) = 2.07 (1.10-3.89), P = 0.024), but not for MetS (OR (95% CI) = 1.12 (0.74-1.69), P = 0.605), after full adjustment. CONCLUSIONS: Our data suggest that age and apparent 11ß-HSD2 activity modulate the association of copeptin with insulin resistance at the population level but not MeTS or diabetes. Further research is needed to corroborate these results and to understand the mechanisms underlying these findings.

Seasonality of sodium and potassium consumption in Switzerland. Data from three cross-sectional, population-based studies.

BACKGROUND AND AIM: Blood pressure displays a seasonal pattern. Whether this pattern is related to high sodium and/or low potassium intakes has not been investigated. We assessed if sodium and potassium consumption present a seasonal pattern. We also simulated the impact of seasonality of sodium consumption on systolic blood pressure levels. METHODS AND RESULTS: Data from three Swiss population-based studies (n = 2845). Sodium and potassium consumption were assessed by urinary excretion using 24 h urine collection. Seasonality was assessed using the cosinor model and was adjusted for study, gender, age, body mass index, antihypertensive drug treatment, urinary creatinine and atmospheric relative humidity. The effect of sodium variation on blood pressure levels was estimated using data from a recent meta-analysis. Both sodium and potassium excretions showed a seasonal pattern. For sodium, the nadir occurred between August and October, and the peak between February and April, with a multivariate-adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For potassium, the nadir occurred in October and the peak in April, with a multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on antihypertensive drug treatment or stratifying the analysis by gender cancelled the seasonality of sodium consumption. The maximum impact of the seasonal variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1 mm Hg, depending on the model considered. CONCLUSION: Sodium and potassium consumptions present specific seasonal variations. These variations do not explain the seasonal variations in blood pressure levels.

Variaciones en la técnica del trasplante limbar autólogo / Variations in the technique for autologous limbal transplantation

OBJETIVO: Presentar los resultados del uso de un único segmento de autoinjerto limbar combinado con trasplante de membrana amniótica y epiteliectomías conjuntivales sectoriales secuenciales postoperatorias en 2 pacientes con insuficiencia límbica unilateral total. CONCLUSIONES: Un solo segmento de autoinjerto limbal junto con el trasplante de membrana amniótica puede ser suficiente para restaurar una superficie corneal estable, siendo en ocasiones necesario realizar en el postoperatorio epiteliectomías conjuntivales secuenciales en zonas remanentes de epitelio anómalo

OBJECTIVE: To present the results on the use of a single block limbal autograft, combined with amniotic membrane transplantation and sectoral sequential postoperative epitheliectomy of the conjunctiva in 2 patients with unilateral total limbal stem cell deficiency. CONCLUSIONS: A single block limbal autograft combined with amniotic membrane transplantation may be sufficient to restore a stable corneal surface, but sometimes sequential sectoral conjunctival epitheliectomy may be required to treat anomalous epithelial remnants

Variations in the technique for autologous limbal transplantation. / Variaciones en la técnica del trasplante limbar autólogo.

OBJECTIVE: To present the results on the use of a single block limbal autograft, combined with amniotic membrane transplantation and sectoral sequential postoperative epitheliectomy of the conjunctiva in 2 patients with unilateral total limbal stem cell deficiency. CONCLUSIONS: A single block limbal autograft combined with amniotic membrane transplantation may be sufficient to restore a stable corneal surface, but sometimes sequential sectoral conjunctival epitheliectomy may be required to treat anomalous epithelial remnants.

Acute and long term mineral metabolism adaptation in living kidney donors: a prospective study.

BACKGROUND: Living kidney donors (LKDs) experience an abrupt decline in glomerular filtration rate (GFR). Mineral metabolism adaptations in early CKD are still debated and not well studied in LKDs. We prospectively studied acute and long term mineral metabolism adaptation of LKDs. METHODS: From May 2010 to December 2012, we included 27 adult LKDs. Their mineral parameters and renal function were repeatedly measured at days 0, 1, 2, 3, 180 and 360 after donation. We also measured in uninephrectomized rats' Klotho in the remnant kidney and FGF23 circulating levels. RESULTS: In the first days after nephrectomy, LKDs experience transient dilution hypocalcemia and secondary hyperparathyroidism. Urinary phosphate reabsorption decreases in spite of an abrupt decline in circulating FGF23 and Klotho. In a more chronic stage, at days 180 and 360 after donation, LKDs have lower GFR and 1,25(OH)2D compared to pre-donation levels, with unchanged 25(OH)D. PTH levels increase, resulting in decreased plasma phosphate levels and renal tubular reabsorption of phosphate. In comparison to pre-donation, FGF23 levels are not significantly changed whereas circulating Klotho levels are lower than pre-donation but higher than immediately post-donation. In uninephrectomized rats, Klotho kidney expression increases after three weeks, whereas circulating FGF23 levels are unchanged. CONCLUSION: From six months after kidney donation, LKDs develop secondary hyperparathyroidism related to a decrease in 1,25(OH)2D, and decreased plasma phosphate levels. FGF23 levels do not rise in LKDs. Middle term mineral metabolism adaptations to decreased eGFR in donors include decrease in 1,25(OH)2D and increase in PTH and fractional excretion of phosphate resulting in lowered plasma phosphate levels, independently of FGF23. These adaptations differ from those described in CKD patients.

[Biomarkers in acute kidney injury: an update]. / Biomarqueurs dans l'insuffisance rénale aiguë.

Acute kidney injury is associated with higher risk of chronic kidney disease or death. Diagnosis is based on increased serum creatinin, most often several days after the initial renal injury. Several novel biomarkers are being studied and validated in clinical settings. Cystatin C, NGAL, KIM-1, IL-18 or L-FABP are the most promising. Their elevation in serum or urine is specifically associated with kidney injury. They seem also to predict mortality and the need of dialysis. In the near future, these biomarkers could affect the way we treat patients with acute kidney injury, as well as their evolution. However, the real challenge will be in using the best combination of biomarkers and in the correct interpretation of their results.

[New radiological techniques to investigate patients suffering from chronic kidney disease]. / Nouvelles techniques radiologiques pour les patients insuffisants rénaux.

Radiological investigations using gadolinium or intravenous iodinated contrast products are used cautiously in patients suffering from chronic kidney disease because of their risk of acute kidney injury and systemic nephrogenic fibrosis. In this article, we review several radiological alternatives that can be useful to obtain renal anatomical and/or functional information in this patient population. The basic principles, indications, and advantages and limitations of Doppler ultrasound with measurement of the resistance index, contrast-enhanced ultrasound, and a technique called BOLD-MRI (blood-oxygenation level dependent-MRI) are discussed.

Acute kidney injury as a risk factor for chronic kidney diseases in disadvantaged populations.

Acute kidney injury (AKI) is considered to be a potential cause for developing chronic kidney disease (CKD); on the other hand, CKD predisposes to AKI. The lack of adequate epidemiological data makes it difficult to determine if AKI induces CKD in less developed countries. The etiology of AKI in rich populations, in whom sophisticated surgery, interventional radiology and oncology treatments are usually the cause of AKI, is very different from that of disadvantaged populations, where the origin of AKI is associated with endemic infections, obstetric problems, poisons, toxins and natural disasters. Any conclusions extrapolated from these two settings should be treated with caution. Moreover, people living in disadvantaged conditions are usually much younger than those in rich areas and this age factor could facilitate total recovery of renal function after AKI if treatment based on an adequate supply of water, rehydration and anti-infectious measures were provided. In the small segment of the population of less developed countries having an income per capita similar to that observed in the developed countries, the long-term outcome of AKI should also be expected to be similar. New data coming from two single centers analyzing only the long-term outcome of acute tubular necrosis (ATN) patients, with a normal or near normal renal function prior to the AKI episode, coincide in reporting a requirement for chronic dialysis among the surviving patients of 2%. If these data are confirmed, the importance of AKI as cause of CKD should be reconsidered, both in developed and less developed countries.

Evolution of rejection rates and kidney graft survival: a historical analysis.

INTRODUCTION: New immunosuppressive regimens have dramatically reduced rejection rates but this positive effect has not been followed by an improvement in long-term graft outcomes. The aim of the present work was to investigate the incidence of graft rejection and graft outcomes with various immunosuppressive protocols. PATIENTS AND METHODS: Included in our study were 1029 first renal transplantations performed at our unit between November 1979 and December 2007. Basal immunosuppression included azathioprine (AZA) in 198 recipients, cyclosporine (CsA) in 524 recipients, and tacrolimus (TAC) in 307 recipients. RESULTS: Recipient and donor ages increased progressively from the AZA to the TAC era. Delayed graft function was less frequent among AZA than CsA and TAC recipients (29.8 vs 39.3% vs 42.0%; P = .014). The incidence of acute rejection episodes was 68.7% on AZA, 38.2% on CsA, and 11.4% on TAC (P = .000). Graft survival rates at 1, 5, and 10 years were 69%, 56%, and 46% on AZA, 82%, 69%, and 54% on CsA, and 88%, 77%, and 60% on TAC, respectively (P = .001). However, the differences disappeared when only grafts surviving >12 months were analyzed. On multivariate analysis, the variables associated with worse graft outcomes after 12 months were older recipient age, male gender, longer time on dialysis, lower body weight, and higher serum creatinine level at 6 months. CONCLUSIONS: New immunosuppressants have decreased the incidence of acute rejection. But this was not followed by a significant improvement in graft outcomes after 12 months. The beneficial effects on rejection are possibly affected by the older age of donor and recipient and the worse early graft function.

Vitamin D deficiency in kidney transplant recipients: risk factors and effects of vitamin D3 supplements.

INTRODUCTION: The Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines in chronic kidney disease (CKD) give some recommendations about diagnosis and treatment of vitamin D deficiency. These guidelines may also be applied to renal transplant recipients. The aim of the present study was to assess the vitamin D status and the effects of vitamin D3 supplements among a cohort of kidney graft recipients. PATIENTS AND METHODS: Five hundred nine renal transplant recipients with a follow-up of more than 12 months were included in this retrospective cross-sectional study. A total of 189 patients were treated with vitamin D3 supplements, 171 with calcitriol (0.25 or 0.5 microg x 3 weekly) and 18 with cholecalciferol (400 IU/d). RESULTS: 25OHD deficiency was present in 38.3% of patients, insufficiency in 46.9%, and normal levels in 14.7%. There were no differences in the prevalence of deficiency or insufficiency between patients who were not treated or those who were treated with vitamin D3 supplements. Upon multivariate analysis, 25OHD concentrations correlated with gender, length of follow-up, season of 25OHD determination, iPTH and 1.25OHD concentrations, and treatment with ACEI/ARB (R(2) = 0.17; P = .000). CONCLUSIONS: 25OHD deficiency or insufficiency is frequent after renal transplantation even in sunny regions. The clinical significance of such a high prevalence of apparent 25OHD deficiency/insufficiency is unclear and requires further study.

Secondary hyperparathyroidism after kidney transplantation: a cross-sectional study.

INTRODUCTION: The purpose of the present study was to investigate the prevalence of hyperparathyroidism among a population of kidney graft recipients. PATIENTS AND METHODS: We investigated biochemical bone parameters of 509 renal transplant recipients with a mean follow-up of 113 +/- 76 months. Among these patients, 257 patients were treated with either vitamin D or calcium supplements or both. RESULTS: The mean estimated glomerular filtration rate (eGFR) was 47.2 +/- 18.4 mL/min/1.73 m(2) and the mean intact parathyroid hormone (iPTH) level was 144 +/- 149 pg/mL. A total of 70 patients (13.7%) had hypercalcemia defined by a corrected serum calcium >10.2 mg/dL. When the patients were classified according to iPTH concentrations following the Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines: 22.4% had iPTH <70 pg/mL; 30.8% between 70 and 110 pg/mL; 16.5% between 110 and 150 pg/mL; 24.3% between 150 and 300 pg/mL; and 6.9% >300 pg/mL. There were no differences in biochemical bone parameters between those that were or were not on calcium and vitamin D supplements, but there was a higher percentage of patients with normal iPTH among the treated group (28.0% vs 16.7%; P = 0.003). In patients not receiving calcium and/or vitamin D supplements, multiple linear regression demonstrated that only time on dialysis, eGFR, and serum 25-hydroxyvitamin D (25OHD) levels were significantly predictive of iPTH concentrations (R(2) = 0.21; P = .000). CONCLUSIONS: About 80% of patients displayed high iPTH concentrations. The persistence of hyperparathyroidism was associated with graft dysfunction, longer time on dialysis, and low concentrations of 25OHD. Treatment with vitamin D produced a slight improvement in the prevalence of hyperparathyroidism.

Teleophthalmology as screening method for diabetic retinopathy

The aim of this study was to evaluate the suitability of teleophthalmologyas a method for screening of diabetic retinopathy. It wasdesigned as a transversal and observational study using the retinalfundus images of 520 patients that were studied during the first sixmonths of 2006. This sample comes from a group of patients thatare integrated in the Program of digital retinal screening. This screeningprogram was established by the Integral Plan of Diabetes in Andalusiain 2005. It was evaluated the quality of images, the pick-uprate of the illness, the accuracy and the efficiency of the method. In90% of the patients, the images possessed quality to be evaluated.The pick-up rate of the illness was 2.1. Agreement between existenceor absence of diabetic retinopathy was analyzed by using unweightedkappa and its results equal 1. In conclusion, the resultsobtained in the study provide evidence for the reliability of telemedicineas a screening method for diabetic retinopathy(U)

[Prevention of contrast nephropathy: myth or reality?]. / Prevention de la néphropathie au produit de contraste: du mythe a la réalité.

Prevention of Contrast Media induced acute renal failure is of importance, especially in patients with chronic renal failure. Vasodilatators such as fenoldopam and prophylactic hemodialysis have been reported to procure disappointing results. Hydratation prior to and post- exposure to contrast media remains the cornerstone of prevention. Urine alcalinisation with sodium bicarbonate may bring additional renoprotection. Use of a small quantity of contrast media and Acetylcysteine concomitantly to hydratation are also recommended.

Preoperative planning with magnetic resonance imaging and computerized volume rendering in twin-to-twin transfusion syndrome.

Our purpose was to illustrate the feasibility of preoperative planning with magnetic resonance imaging, 3-dimensional reconstruction, and volume-rendering techniques in twin-to-twin transfusion syndrome treated by endoscopic laser ablation of communicating vessels. After ultrasonographic determination of the syndrome and the indications for intervention, 2 patients with an anterior placenta underwent magnetic resonance imaging without the need for maternal or fetal sedation. Raw image data were downloaded into a desktop computer and manipulated with 3-dimensional reconstruction, volume rendering, and surgical navigation software. In both patients a virtual rendering of the fetuses, placenta, and uterus could be manipulated to expose all sides, demonstrate the location of the intertwin membrane, and plan the point of entry and curve of the endoscopic instruments. Preoperative planning and virtual surgical navigation in fetal surgery are now possible, as a result of shorter magnetic resonance imaging acquisition times and volume-rendering software. In this manner an entire virtual endoscopic fetal operation can be performed and fine-tuned before the actual procedure is to take place.

Oocysts, IgG levels and immunoblot patterns determined for Cryptosporidium parvum in bovine examined during a visit to a farm (northeastern Spain).

Single fecal and serum samples were individually collected from 101 bovines selected at random during a visit to a farm in northeastern Spain (Group I, 26 animals aged 2-36 days; Group II, 34 animals aged 1.5-4.5 months; Group III, 41 animals aged 20-24 months). Testing for the presence of Cryptosporidium parvum oocysts in feces (Monofluo Kit Cryptosporidium, Diagnostics Pasteur, France) indicated that 26% animals were infected (81% of Group I, 15% of Group II and 0% of Group III). Serological testing (ELISA for detection of specific anti-C. parvum IgG) indicated that 59% animals were seropositive (12% of Group I, 74% of Group II and 78% of Group III). Immunoblotting results indicate that cattle sera recognize C. parvum antigens of widely varying molecular weights and that the number of antigens recognized increases with age. Immunoblots revealed that some of the sera belonging to the Group I reacted with protein fractions between 15 and 20 kDa but none recognized the 21-23 kDa antigen. Only few sera in the Group II recognized the protein fraction between 15 and 20 kDa. The recognition of 21-23 kDa fraction was observed by four sera from uninfected and seropositive animals. Sera from all the seronegative Group II animals recognized few antigens and always with molecular weight greater than 50 kDa. Serum samples from both seropositive and seronegative animals belonging to the Group III recognized antigens with molecular weight ranging 15-20 kDa. Surprisingly, the protein fractions between 21 and 28 kDa reacted with approximately 30% of the sera from seropositive animals and only one of the nine sera from seronegative animals. The recognition of 42-46 kDa antigens increased with the age and only reacted with the sera from uninfected animals.

Effect of a commercial disinfectant ('Virkon') on mouse experimental infection by Cryptosporidium parvum.

Cryptosporidium parvum oocysts obtained from naturally-infected calves were exposed to 1-10% 'Virkon' for 10-360 min, then inoculated intragastrically into coccidium-free neonatal mice. Prevalence and intensity of infection were determined seven days later by examination of intestinal homogenates. Although we were unable to abolish infectivity for the mice, the intensity of infection was considerably reduced after long periods of exposure (up to > 90%, depending on disinfectant concentration), indicating that this product may have some value for disinfection when extended exposure is possible (e.g., soaking laboratory glassware).

Autonomic neurons supplying the rat eye and the intraorbital distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactivity.

We traced the origin and path of autonomic nerves to the rat eye using, as an aid to dissection, a modified thiocholine method for the histochemical demonstration of cholinesterase. When applied to whole nerves and ganglia supplying the rat eye, this procedure is not specific for cholinergic neurons; instead it stains both sympathetic and parasympathetic nerves, many of which are otherwise too fine to identify in dissection. We found that nerves from the superior cervical and pterygopalatine ganglia form a plexus at the orbital apex corresponding to the retro-orbital plexus found in rabbit, monkey and man. In the rat, nerves from the retro-orbital plexus travel peripherally to the superior surface of the optic-nerve sheath. Here, they fuse with long ciliary nerves and the post-ganglionic nerves from the ciliary ganglion to form another dense nerve-fiber plexus that ultimately supplies the eye. Importantly, the plexus on the optic nerve contains many isolated or aggregated ganglion cells. These are comparable in number to those in the ciliary ganglion itself and are assumed to be accessory ciliary neurons. Using immunohistochemistry, we also sought evidence for vasoactive intestinal polypeptide in these ganglia and nerves. As previously known, many pterygopalatine ganglion cells are immunoreactive for this peptide. Vasoactive intestinal polypeptide (VIP)-like immunoreactive nerve fibers are present in nerves from the retro-orbital plexus to the optic-nerve sheath plexus, in most nerves of the latter plexus, and in most nerves entering the eye. Furthermore, a small proportion of nerve cells in the main and accessory ciliary ganglia also are immunoreactive for VIP. We conclude that in addition to the pterygopalatine ganglion, the ciliary ganglion and its accessory ganglia are sources of VIP-like immunoreactive nerves in the rat eye.