Photodynamic therapy for atherosclerosis. The potential of indocyanine green.

AIM: The aim of this article is to summarize and review the use of photodynamic therapy for the treatment of atherosclerotic plaque and the prevention of intimal hyperplasia. Different photosensitizers are discussed and more specifically the role of indocyanine green as a potential photosensitizer. METHODS: Literature search with focus on the use of photodynamic therapy in atherosclerosis, the mechanism of action and the different photosensitizers for photodynamic therapy. RESULTS: In-vitro and in-vivo studies confirm the possibilities of using photodynamic therapy for the treatment of atherosclerosis and the prevention of restenosis. Insufficient specificity in the accumulation of photosensitizer and thus phototoxicity, remains an important problem. Indocyanine green is a photosensitizer with features in favor of photodynamic therapy. Results obtained so far of photodynamic therapy with indocyanine green point towards the potential of indocyanine green as a photosensitizer in photodynamic therapy for atherosclerosis. CONCLUSION: Photodynamic therapy is a promising tool for treating atherosclerosis. Many of the studied photosensitizers have toxic effects. Indocyanine green might be a good photosensitizer for the use of photodynamic therapy in atherosclerosis. These data justify further research to the use of indocyanine green as a photosensitizer in the treatment of atherosclerotic plaque both de novo or in restenotic lesions.

Compound A influences gene regulation of the Dexamethasone-activated glucocorticoid receptor by alternative cofactor recruitment.

The glucocorticoid receptor (GR) is a transcription factor of which the underlying gene regulatory mechanisms are complex and incompletely understood. The non-steroidal anti-inflammatory Compound A (CpdA), a selective GR modulating compound in various cell models, has been shown to favour GR-mediated gene repression but not GR-mediated gene activation. Shifting balances towards only a particular subset of GR gene regulatory events may be of benefit in the treatment of inflammatory diseases. We present evidence to support that the combination of CpdA with Dexamethasone (DEX), a classic steroidal GR ligand, can shape GR function towards a unique gene regulatory profile in a cell type-dependent manner. The molecular basis hereof is a changed GR phosphorylation status concomitant with a change in the GR cofactor recruitment profile. We subsequently identified and confirmed the orphan nuclear receptor SHP as a coregulator that is specifically enriched at GR when CpdA and DEX are combined. Combining CpdA with DEX not only leads to stronger suppression of pro-inflammatory gene expression, but also enhanced anti-inflammatory GR target gene expression in epithelial cells, making ligand combination strategies in future a potentially attractive alternative manner of skewing and fine-tuning GR effects towards an improved therapeutic benefit.

Epidemiological study on chronic venous disease in Belgium and Luxembourg: prevalence, risk factors, and symptomatology.

OBJECTIVE: This epidemiological study measured the prevalence of chronic venous disease (CVD) in Belgium and Luxembourg. Possible risk factors and the symptomatology were evaluated. MATERIAL AND METHODS: A survey was carried out in Belgium and Luxembourg between May and September 2013. Patient recruitment was carried out by 406 general practitioners (GPs). Each GP screened 10-20 consecutive patients older than 18 years, and in total 6009 patients were included. Patient characteristics, prevalence of risk factors, symptomatology, and C-classification were noted. The GPs diagnosed CVD and measured the need for treatment. Patients with diagnosed CVD completed a questionnaire about their history of leg problems and a quality of life score (CIVIQ-14). These data were converted into a CIVIQ Global Index Score (GIS). RESULTS: The mean age of the patients was 53.4 years, and they were predominantly female (67.5%). Among the 3889 symptomatic patients, heavy legs, pain, and sensation of leg swelling were the most common complaints. Among the included patients, 61.3% of patients were classified within C1-C6; however, only 45.9% of these patients were considered by the GPs to be suffering CVD. Treatment was offered to 49.5% of patients. Age and female gender correlate with a higher C-class (p < .001). Patients with a higher C-class (C3-C6) have significantly more pain, sensation of swelling and burning, night cramps, itching, and the sensation of "pins and needles" in the legs. Patients taking regular exercise and without a family history had a lower C-class. Higher BMI, age, female gender, family history, history of thrombophlebitis, and a higher C-class correlated with a lower GIS (p < .001). Of the patients with CVD, 10.4% had lost days of work because of their venous leg problems. CONCLUSION: CVD is a very common disease, which is underestimated. The prevalence increases with age, generates incapacity to work, and worsens the patients' quality of life.

Endovenous laser ablation of the great saphenous vein using a bare fibre versus a tulip fibre: a randomised clinical trial.

OBJECTIVE: This clinical trial aimed to evaluate the clinical results of the use of a tulip fibre versus the use of a bare fibre for endovenous laser ablation. METHODS: In a multicentre prospective randomised trial 174 patients were randomised for the treatment of great saphenous vein reflux. A duplex scan was scheduled 1 month, 6 months and 1 year postoperatively. Ecchymosis was measured on the 5th postoperative day. In addition, pain, analgesics requirement, postoperative quality of life (CIVIQ 2) and patient satisfaction rate were noted. RESULTS: Patients treated with a tulip fibre had significantly less postoperative ecchymosis (0.04 vs. 0.21; p < 0.001) and pain (5th day) (1.00 vs. 2.00; p < 0.001) and had a better postoperative quality of life (27 vs. 32; p = 0.023). There was no difference in analgesic intake (p = 0.11) and patient satisfaction rate (p = 0.564). The total occlusion rate at 1 year was 97.02% and there was no significant difference between the two groups (p = 0.309). CONCLUSION: Using a tulip fibre for EVLA of the great saphenous vein results, when compared with the use of a bare fibre, in equal occlusion rates at 1 year but causes less postoperative ecchymosis and pain and in a better postoperative quality of life.

Discovery of a large set of SNP and SSR genetic markers by high-throughput sequencing of pepper (Capsicum annuum).

Genetic markers based on single nucleotide polymorphisms (SNPs) are in increasing demand for genome mapping and fingerprinting of breeding populations in crop plants. Recent advances in high-throughput sequencing provide the opportunity for whole-genome resequencing and identification of allelic variants by mapping the reads to a reference genome. However, for many species, such as pepper (Capsicum annuum), a reference genome sequence is not yet available. To this end, we sequenced the C. annuum cv. "Yolo Wonder" transcriptome using Roche 454 pyrosequencing and assembled de novo 23,748 isotigs and 60,370 singletons. Mapping of 10,886,425 reads obtained by the Illumina GA II sequencing of C. annuum cv. "Criollo de Morelos 334" to the "Yolo Wonder" transcriptome allowed for SNP identification. By setting a threshold value that allows selecting reliable SNPs with minimal loss of information, 11,849 reliable SNPs spread across 5919 isotigs were identified. In addition, 853 single sequence repeats were obtained. This information has been made available online.

Endovenous laser treatment: is there a clinical difference between using a 1500 nm and a 980 nm diode laser? A multicenter randomised clinical trial.

AIM: We compared the use of two different laser wavelengths in the treatment of great saphenous vein (GSV) reflux: the 1500 nm versus the 980 nm diode laser. We studied the occlusion rates and noted possible side-effects. METHODS: In three centers 180 great saphenous veins were treated with endovenous laser ablation (EVLA). By random selection half of the patients were treated with a 980 nm laser and half with a 1500 nm laser. A Duplex scan was scheduled at one month and six months postoperatively. Ecchymosis was measured at one week using a calculated scale. In addition the need for analgesics, the induration around the treated vein and patient satisfaction rate were noted. At two weeks postoperatively a quality of life score (CIVIQ2) was obtained. RESULTS: The complete occlusion rates at six months were not statistical significant different between both groups (95.5% for 980 nm and 93.1% for 1500 nm). Most of the non-occluded veins had a filiform internal lumen and did not show reflux. There was no significant difference in the postoperative appearance of ecchymosis (P=0.09). Patients treated with a 1500 laser had less induration around the treated vein (P=0.002), less need to take analgetics (1.8 days versus 2.9 days) and had a better postoperative quality of life (P=0.018). The patient satisfaction rate did not differ in the two groups. CONCLUSION: Using a 1500 nm diode laser in the treatment of an incompetent GSV, compared to the use of a 980 nm laser, results in similar occlusion rates at six months, but somewhat less side-effects.

Endovenous laser ablation: the role of intraluminal blood.

OBJECTIVE: In this histological study, the role of the intraluminal blood during endovenous laser ablation was assessed. METHODS: In 12 goats, 24 lateral saphenous veins were treated with a 1500-nm diode laser. Four goats were treated in an anti-Trendelenburg position (group 1). The next four goats were treated in a Trendelenburg position (group 2) and the remaining four goats in the Trendelenburg position with additional injection of tumescent liquid (group 3). Postoperatively, the veins were removed after 1 week and sent for histological examination. We measured the number of perforations. Vein wall necrosis and the perivenous tissue destruction were quantified using a graded scale. RESULTS: The 'calculated total vein wall destruction' was significantly higher in the third group (81.83%), as compared with groups one (61.25%) (p < 0.001) and two (65.92%) (p < 0.001). All three groups showed a significant difference in the perivenous tissue destruction scale (p < 0.001) with the lowest score occurring in the third group. Vein wall perforations were significantly more frequent in groups one and two as compared with the third group (T-test respectively p < 0.001, p = 0.02). CONCLUSION: A higher intraluminal blood volume results in reduced total vein wall destruction. Injection of tumescent liquid prevents the perivenous tissue destruction and minimises the number of perforations.

Use of a new endovenous laser device: results of the 1,500 nm laser.

BACKGROUND: A new endovenous laser wavelength (1,500 nm diode laser) in the treatment of great saphenous vein (GSV) reflux was evaluated. We studied the occlusion rate at 6 months and noted possible side effects. METHODS: In 129 patients, 158 GSVs were treated using the 1,500 nm diode laser. An average linear endovenous energy density of 53.4 J/cm and an average endovenous fluence of 32.21 J/cm(2) were administrated to the vein. RESULTS: The occlusion rate at 6 months postoperative was 93.3%. Some of the nonoccluded veins closed spontaneously. A postoperative foam treatment was necessary in 3.4% of the treated veins. We found a marked shrinkage of the treated veins. There were limited side effects: moderate or severe ecchymosis in 19%, moderate pain in 1%, moderate periphlebitis in 8.2%, with no paresthesias. CONCLUSION: Endovenous laser treatment of the GSV using a 1,500 nm diode laser is effective and safe. The marked shrinkage of the treated veins can guarantee good long-term results.

Intraluminal fibre-tip centring can improve endovenous laser ablation: a histological study.

OBJECTIVE: In this histological study, the lateral saphenous vein of the goat was treated using a laser fibre to which a tulip-shaped, self-expandable catheter had been fixed to achieve endovenous laser ablation (EVLA). The catheter centres the laser fibre in the vein preventing direct contact with the vein wall. This study aims to establish whether prevention of direct contact between the fibre tip and the vein wall prevents ulceration and perforation of the vein wall and perivenous tissue destruction. MATERIALS AND METHODS: Ten lateral saphenous veins were treated, using the tulip catheter, in goats under general anaesthesia. Ten more veins were treated with a normal bare fibre. We used a 980 nm diode laser to provide the energy. Postoperatively the veins were removed immediately, at 10 days and after 3 weeks for histological examination. Destruction of the vessel wall was measured and perivenous tissue destruction was quantified using a graded scale. RESULTS: Ulceration and perforation were prevented when using the tulip catheter. It also achieved more even vein wall necrosis. Tulip-catheter-treated veins show a transmural vein wall necrosis in, on average, 80% of the total circumference compared to 64% in bare-fibre treated veins. Less perivenous tissue destruction was seen with the new catheter (perivenous tissue destruction scale: tulip catheter: 1.7 vs. bare fibre: 3.8). Three weeks after treatment, we found regression of the perivenous tissue destruction as the healing process continued. CONCLUSIONS: EVLA using the tulip catheter avoids ulceration and perforation of the vein associated with treatment using a bare fibre. It also results in more even circumferential vein wall necrosis and less perivenous tissue destruction.

Endovenous laser treatment: a morphological study in an animal model.

OBJECTIVES: The destruction induced during endovenous laser treatment (ELT) of the saphenous vein and the perivenous tissue in an animal model (goats) was analysed. Differences in vein wall destruction produced by two laser types, the 980 and 1500 nm diode lasers, were evaluated histologically. METHODS: In 14 goats, 28 lateral saphenous veins were treated with ELT. In 14 veins we used the 980 nm diode laser and in the remnant a 1500 nm laser. Postoperatively the veins were removed at different stages and sent for histological examination. RESULTS: Immediately removed veins after ELT show an uneven destruction of the vein wall. Veins harvested one week postoperatively show inflammatory tissue at their periphery. Two and three weeks postoperatively, organization is very extensive. In some cases, recanalization begins in a semi-lunar manner at the contralateral side of the laser hit. Veins treated with a 980 nm laser show deeper ulceration with more perivenous tissue destruction compared with veins treated with a 1500 nm diode laser. CONCLUSIONS: The ELT of veins produces an unevenly distributed damage. The cell necrosis is far more extensive than expected. Uneven vein wall destruction can lead to recanalization. Using a 1500 nm laser correlates with less penetrating ulcerations and more circumferential damage.

Lost gallstones: a relaparoscopic solution to laparoscopic pollution.

This case report describes the treatment by radiological intervention combined with therapeutic relaparoscopy of a patient with a gluteolumbar fistula due to lost gallstones 5 years after laparoscopic cholecystectomy.

Chromosomal regions involved in hybrid performance and heterosis: their AFLP(R)-based identification and practical use in prediction models.

In this paper, a novel approach towards the prediction of hybrid performance and heterosis is presented. Here, we describe an approach based on: (i) the assessment of associations between AFLP(R) markers and hybrid performance and specific combining ability (SCA) across a set of hybrids; and (ii) the assumption that the joint effect of genetic factors (loci) determined this way can be obtained by addition. Estimated gene effects for grain yield varied from additive, partial dominance to overdominance. This procedure was applied to 53 interheterotic hybrids out of a 13 by 13 half-diallel among maize inbreds, evaluated for grain yield. The hybrid value, representing the joint effect of the genetic factors, accounted for up to 62.4% of the variation in the hybrid performance observed, whereas the corresponding efficiency of the SCA model was 36.8%. Efficiency of the prediction for hybrid performance was evaluated by means of a cross-validation procedure for grain yield of (i) the 53 interheterotic hybrids and (ii) 16 hybrids partly related to the 13 by 13 half-diallel. Comparisons in prediction efficiency with the 'distance' model were made. Because the map position of the selected markers is known, putative quantitative trait loci (QTL) affecting grain yield, in terms of hybrid performance or heterosis, are identified. Some QTL of grain yield detected in the present study were located in the vicinity of loci reported earlier as having quantitative effects on grain yield.

A 5-year prospective randomized clinical trial on the influence of splinted and unsplinted oral implants retaining a mandibular overdenture: prosthetic aspects and patient satisfaction.

Prosthetic outcome and patient satisfaction were evaluated in order to investigate whether there is a need or advantage to splint two implants in the mandible retaining a hinging overdenture. This study included 36 fully edentulous patients randomly divided into three groups according to the attachment system they received: magnets, ball attachments or straight bars (reference group). None of the implants failed during the whole observation period in any of the groups. After 5 years of observation, the Bar group presented the highest retention capacity and the least prosthetic complications but revealed more mucositis and gingival hyperplasia. Patient satisfaction rated similar for all groups although the Magnet group showed lower retention forces. All patients would repeat the same treatment even though the majority of the Magnet group would prefer a more retentive solution because of limited denture stability.

A 5-year randomized clinical trial on the influence of splinted and unsplinted oral implants in the mandibular overdenture therapy. Part I: Peri-implant outcome.

Thirty-six completely edentulous patients were enrolled for a 5-year prospective study testing the treatment outcome between splinted and unsplinted implants retaining a mandibular hinging overdenture. The patients were randomized into 3 groups of equal size depending on the attachment system used such as: magnets, ball attachments or bars (reference group). Only 1 implant out of the 72 had failed at the abutment stage. Not a single implant failed during the 5-year loading period. The accumulation of plaque was significantly higher for the Magnet than for the Ball group. Bleeding on probing, as well as marginal bone level, attachment level and Periotest values did not statistically differ among the groups, neither at year 1 nor at year 5. However, the Periotest values were significantly lower at year 5 compared to year 1 for all groups, which indicates a higher rigidity at the bone-implant interface. No correlation was found between bleeding on probing and marginal bone loss. We conclude that the connection state of 2 implants retaining a hinging overdenture did not influence the peri-implant outcome.

Prediction of testcross means and variances among F3 progenies of F1 crosses from testcross means and genetic distances of their parents in maize.

Prediction of the means and genetic variances in segregating generations could help to assess the breeding potential of base populations. In this study, we investigated whether the testcross (TC) means and variances of F3 progenies from F1 crosses in European maize can be predicted from the TC means of their parents and F1 crosses and four measures of parental genetic divergence: genetic distance (GD) determined by 194 RFLP or 691 AFLP(TM) (1) markers, mid-parent heterosis (MPH), and absolute difference between the TC means of parents (∣P1-P2∣). The experimental materials comprised six sets of crosses; each set consisted of four elite inbreds from the flint or dent germplasm and the six possible F1 crosses between them, which were evaluated for mid-parent heterosis. Testcross progenies of these materials and 20 random F3 plants per F1 cross were produced with a single-cross tester from the opposite heterotic group and evaluated in two environments. The characters studied were plant height, dry matter content and grain yield. The genetic distance between parent lines ranged between 0.17 and 0.70 for RFLPs and between 0.14 and 0.57 for AFLPs in the six sets. Testcross-means of parents, F1 crosses, and F3 populations averaged across the six crosses in a particular set generally agreed well for all three traits. Bartlett's test revealed heterogeneous TC variances among the six crosses in all sets for plant height, in four sets for grain yield and in five sets for dry matter content. Correlations among the TC means of the parents, F1 crosses, and F3 populations were highly significant and positive for all traits. Estimates of the TC variance among F3 progenies for the 36 crosses showed only low correlations with the four measures of parental genetic divergence for all traits. The results demonstrated that for our material, the TC means of the parents or the parental F1 cross can be used as predictors for the TC means of F3 populations. However, the prediction of the TC variance remains an unsolved problem.

A randomised clinical trial on the influence of splinted and unsplinted oral implants in mandibular overdenture therapy. A 3-year report.

A randomised clinical trial was performed to investigate whether there is a need or advantage to splint two implants in the mandible retaining a hinging overdenture. Furthermore, patient satisfaction was evaluated for different attachment systems retaining the overdenture. Thirty-six edentulous patients were randomised into three groups of equal size and treated with either magnets, ball attachments or straight bars (reference group). After 3 years of observation no implants were lost in any of the groups. Besides, no statistically significant differences were noted for the peri-implant outcome. Although the bar group presented the highest retention force, the general satisfaction of the patients in the three groups did not differ. The patients with bar retentions showed less prosthetic complications of the retention elements but more at the level of the denture-supporting mucosa. Finally, the clinical outcome of all groups confirms that overdenture treatment demands regular controls with limited time intervals.