Diabetic retinopathy: morphometric analysis of basement membrane thickening of capillaries in different retinal layers within arterial and venous environments

AIMS: To assess quantitatively variations in the extent of capillary basement membrane (BM) thickening between different retinal layers and within arterial and venous environments during diabetes. METHODS: One year after induction of experimental (streptozotocin) diabetes in rats, six diabetic animals together with six age-matched control animals were sacrificed and the retinas fixed for transmission electron microscopy (TEM). Blocks of retina straddling the major arteries and veins in the central retinal were dissected out, embedded in resin, and sectioned. Capillaries in close proximity to arteries or veins were designated as residing in either an arterial (AE) or a venous (VE) environment respectively, and the retinal layer in which each capillary was located was also noted. The thickness of the BM was then measured on an image analyser based two dimensional morphometric analysis system. RESULTS: In both diabetics and controls the AE capillaries had consistently thicker BMs than the VE capillaries. The BMs of both AE and VE capillaries from diabetics were thicker than those of capillaries in the corresponding retinal layer from the normal rats (p <or = 0.005). Also, in normal AE and VE capillaries and diabetic AE capillaries the BM in the nerve fibre layer (NFL) was thicker than that in either the inner (IPL) or outer (OPL) plexiform layers (p <or = 0.001). However, in diabetic VE capillaries the BMs of capillaries in the NFL were thicker than those of capillaries in the IPL (p <or = 0.05) which, in turn, had thicker BMs than capillaries in the OPL (p <or = 0.005). CONCLUSIONS: The variation in the extent of capillary BM thickening between different retinal layers within AE and VE environments may be related to differences in levels of oxygen tension and oxidative stress in the retina around arteries compared with that around veins.

Diabetic retinopathy:morphometric analysis of basement membrane thickening of capillaries in different retinal layers within arterial and venous environments

AIMS: To assess quantitatively variations in the extent of capillary basement membrane (BM) thickening between different retinal layers and within arterial and venous environments during diabetes.

METHODS: One year after induction of experimental (streptozotocin) diabetes in rats, six diabetic animals together with six age-matched control animals were sacrificed and the retinas fixed for transmission electron microscopy (TEM). Blocks of retina straddling the major arteries and veins in the central retinal were dissected out, embedded in resin, and sectioned. Capillaries in close proximity to arteries or veins were designated as residing in either an arterial (AE) or a venous (VE) environment respectively, and the retinal layer in which each capillary was located was also noted. The thickness of the BM was then measured on an image analyser based two dimensional morphometric analysis system.

RESULTS: In both diabetics and controls the AE capillaries had consistently thicker BMs than the VE capillaries. The BMs of both AE and VE capillaries from diabetics were thicker than those of capillaries in the corresponding retinal layer from the normal rats (p < or = 0.005). Also, in normal AE and VE capillaries and diabetic AE capillaries the BM in the nerve fibre layer (NFL) was thicker than that in either the inner (IPL) or outer (OPL) plexiform layers (p < or = 0.001). However, in diabetic VE capillaries the BMs of capillaries in the NFL were thicker than those of capillaries in the IPL (p < or = 0.05) which, in turn, had thicker BMs than capillaries in the OPL (p < or = 0.005).

CONCLUSIONS: The variation in the extent of capillary BM thickening between different retinal layers within AE and VE environments may be related to differences in levels of oxygen tension and oxidative stress in the retina around arteries compared with that around veins.

Étude de prévention de la thrombose veineuse associée au cathéter veineux central de type PICC chez les patients en oncologie recevant une chimiothérapie

Nous avons mené une étude prospective randomisée dans le but de comparer l'effet de l'irrigation du cathéter de type PICC avec deux types d'anticoagulants: Héparine standard et Tinzaparine, une héparine de faible poids moléculaire. Notre étude s'adresse aux patients de la clinique externe d'oncologie de l'hôpital Maisonneuve-Rosemont. Entre début Mai 2005 et Mars 2008, nous avons recruté 131 patients dont 70 ont été randomisés. Parmi les 61 patients exclus, 23 n'ont pas rencontré les critères d'inclusion, 30 ont refusé de participer et 8 ne sont pas inclus pour d'autres raisons. Sur les 70, 36 sujets sont randomisés dans le groupe Héparine standard et 34 dans le groupe Tinzaparine. La population en intention de traiter comprend 65 sujets dont 32 dans le groupe Héparine standard et 33 dans le groupe Tinzaparine. Le médicament a été administré pendant un mombre maximal de 30 jours et les sujets ont été suivis pendant 90 jours. La thrombose veineuse associée au cathéter (TVAC) a été objectivée par une phlébographie ou une échographie-Doppler à la fin de la période de 30 jours suivant l'installation du cathéter. L'incidence de la TVAC sur 30 jours est de 14,39 par 1000 cathéter-jours (IC à 95%:[9,0;19,79]/1000 cathéter-jours ou 41,5% (27/65). L'incidence de la thrombose veineuse profonde (TVP) symptômatique du membre supérieur sur la période de suivi de 90 jours est de 0,41 par 1000 cathéter-jours (IC à 95%:[0,08;0,81]/1000 cathéter-jours ou 3% (2/65). Nous n'avons observé aucune différence entre les deux groupes par rapport à la fréquence de la TVAC ni de la TVP. Nous ne pouvons conclure à une différence dans l'efficacité de la Tinzaparine par rapport à l'Héparine standard dans la prévention de la TVAC.

Increased implantation and pregnancy rates obtained by placing the tip of the transfer catheter in the central area of the endometrial cavity

The influence of endometrial cavity length (ECL) on implantation and pregnancy rates after 400 embryo transfers was studied prospectively in a population with the indication of IVF/intracytoplasmic sperm injection (ICSI). The tip of the transfer catheter was placed above or below the half point of the ECL in a randomized manner. Two analyses were performed: (i) absolute position (AP); embryo transfers were divided into three groups according to the distance between the end of the fundal endometrial surface and the catheter tip (DTC - distance tip catheter): AP 1 (n = 212), 10-15 mm; AP 2 (n = 158), 16-20 mm; and AP 3 (n = 30), ≥21 mm. (ii) relative position (RP) - embryo transfers were divided into four groups according to their RP [RP = (DTC/ECL) × 100]: RP 1 (n = 23), ≤40%; RP 2 (n = 177), 41-50%; RP 3 (n = 117), 51-60%; and RP 4 (n = 83), ≥61%. Analysis based on relative distance revealed significantly higher implantation and pregnancy rates (P < 0.05) in more central areas of the ECL. However, analysis based on absolute position did not reveal any difference. In conclusion, the present results demonstrated that implantation and pregnancy rates are influenced by the site of embryo transfer, with better results being obtained when the catheter tip is positioned close to the middle area of the endometrial cavity. In this respect, previous analysis of the ECL is the fundamental step in establishing the ideal site for embryo transfers.

Comparison of venous plasma glycemia and capillary glycemia for the screening of type 2 diabetes mellitus in the Japanese-Brazilian community of Mombuca (Guatapará-SP)

Abstract Background To identify the most appropriate cut-off points of fasting glycemia for the screening of diabetes mellitus type 2 (DM2) with the comparison of the properties of capillary glycemia (CG) and venous blood plasma glycemia (PG) in a population of Japanese origin from the community of Mombuca, Guatapará - SP, Brazil. Methods This was a population-based descriptive cross-sectional study conducted on a sample of 131 individuals of both genders aged 20 years or more (66.8% of the target population). CG was measured with a glucometer in a blood sample obtained from the fingertip and PG was determined by an enzymatic method (hexokinase) in venous blood plasma, after a 10-14 hour fast in both cases. Data were analyzed by the receiver operating characteristic (ROC) curve in order to identify the best cut-off point for fasting glycemia (CG and PG) for the diagnosis of DM, using the 2-hour plasma glycemia > 200 mg/dl as gold - standard. Results The ROC curve revealed that the best cut-off point for the screening of DM was 110 mg/dl for CG and 105 mg/dl for PG, values that would optimize the relation between individuals with positive and false-positive results. The area under the ROC curve was 0.814 for CG (p < 0.01) and 0.836 for PG (p < 0.01). Conclusions The cut-off points of 105 mg/dl(5.8 mmol/l) for PG and of 110 mg/dl(6.1 mmol/l) for CG appear to be the most appropriate for the screening of DM2 in the population under study, with emphasis on the fact that the value recommended for CG is 5 mg/dl higher than that for PG, in contrast to WHO recommendations.

A standardized protocol for the prevention of clinically relevant venous air embolism during neurosurgical interventions in the semisitting position

OBJECTIVE: We report the results and complications associated with standardized intraoperative management designed for the prevention of hemodynamically relevant venous air embolism during surgery performed in the semisitting position. METHODS: A protocol for preoperative evaluation and intraoperative monitoring was developed and applied in 187 consecutive patients who underwent surgery in the semisitting position between 1999 and 2004. The protocol included preoperative transesophageal echocardiography examination (TEE), intraoperative TEE monitoring, catheterization of the right atrium and a combination of fluid input, positive end expiratory pressure, and standardized positioning aiming at a positive pressure in the transverse and sigmoid sinuses. Data were collected retrospectively from the charts and intraoperative anesthesiological protocols of the patients for the incidence of clinically relevant air embolism (i.e., TEE-diagnosed air embolism plus a decrease in end tidal CO2 or hemodynamic changes) and other complications related to the semisitting position. RESULTS: Three cases (1.6%) of relevant venous air embolism occurred in 187 patients. Only 1 case (0.5%) was hemodynamically relevant, with temporary arterial blood pressure decrease and heart rate increase. Pneumatocephalus leading to lethargy was a frequent postoperative finding, which resolved spontaneously in all except 1 patient with epileptic seizure and oculomotor nerve palsy attributable to space-occupying subdurally trapped air, which had to be treated surgically. There was no permanent morbidity or mortality related to the semisitting position. CONCLUSION: Fear of massive venous air embolism is one reason for dramatic decline in the use of the semisitting position in neurosurgical practice. We found that strict adherence to a standardized protocol using TEE monitoring before and during surgery; exclusion of patients with patent foramen ovale; and a combination of positive end expiratory pressure, fluid input, and a standardized position aiming a positive pressure in the transverse and sigmoid sinuses helped to greatly minimize this complication to a rate of 0.5% for hemodynamically relevant events.

Design and establishment of a biobank in a multicenter prospective cohort study of elderly patients with venous thromboembolism (SWITCO65+)

In the field of thrombosis and haemostasis, many preanalytical variables influence the results of coagulation assays and measures to limit potential results variations should be taken. To our knowledge, no paper describing the development and maintenance of a haemostasis biobank has been previously published. Our description of the biobank of the Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+) is intended to facilitate the set-up of other biobanks in the field of thrombosis and haemostasis. SWITCO65+ is a multicentre cohort that prospectively enrolled consecutive patients aged ≥65 years with venous thromboembolism at nine Swiss hospitals from 09/2009 to 03/2012. Patients will be followed up until December 2013. The cohort includes a biobank with biological material from each participant taken at baseline and after 12 months of follow-up. Whole blood from all participants is assayed with a standard haematology panel, for which fresh samples are required. Two buffy coat vials, one PAXgene Blood RNA System tube and one EDTA-whole blood sample are also collected at baseline for RNA/DNA extraction. Blood samples are processed and vialed within 1 h of collection and transported in batches to a central laboratory where they are stored in ultra-low temperature archives. All analyses of the same type are performed in the same laboratory in batches. Using multiple core laboratories increased the speed of sample analyses and reduced storage time. After recruiting, processing and analyzing the blood of more than 1,000 patients, we determined that the adopted methods and technologies were fit-for-purpose and robust.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

BACKGROUND Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is an update of a review first published in February 2012. OBJECTIVES To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis. SEARCH METHODS For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2013), CENTRAL (2013, Issue 5), and clinical trials registries (up to June 2013). SELECTION CRITERIA Randomised controlled trials (RCTs) comparing any oral or parenteral anticoagulant or mechanical intervention to no intervention or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS Data were extracted on methodological quality, patients, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS We identified 12 additional RCTs (6323 patients) in the updated search so that this update considered 21 trials with a total of 9861 patients, all evaluating pharmacological interventions and performed mainly in patients with advanced cancer. Overall, the risk of bias varied from low to high. One large trial of 3212 patients found a 64% (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.60) reduction of symptomatic VTE with the ultra-low molecular weight heparin (uLMWH) semuloparin relative to placebo, with no apparent difference in major bleeding (RR 1.05, 95% CI 0.55 to 2.00). LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (RR 0.53, 95% CI 0.38 to 0.75; no heterogeneity, Tau(2) = 0%) with similar rates of major bleeding events (RR 1.30, 95% CI 0.75 to 2.23). In patients with multiple myeloma, LMWH was associated with a significant reduction in symptomatic VTE when compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83), while the difference between LMWH and aspirin was not statistically significant (RR 0.51, 95% CI 0.22 to 1.17). No major bleeding was observed in the patients treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against inactive control and found an incidence of major bleeding of 1% in both study groups while not reporting on VTE. When compared with placebo, warfarin was associated with a statistically insignificant reduction of symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20). Antithrombin, evaluated in one study involving paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control. The new oral factor Xa inhibitor apixaban was evaluated in a phase-II dose finding study that suggested a promising low rate of major bleeding (2.1% versus 3.3%) and symptomatic VTE (1.1% versus 10%) in comparison with placebo. AUTHORS' CONCLUSIONS In this update, we confirmed that primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. In addition, the uLMWH semuloparin significantly reduced the incidence of symptomatic VTE. However, the broad confidence intervals around the estimates for major bleeding suggest caution in the use of anticoagulation and mandate additional studies to determine the risk to benefit ratio of anticoagulants in this setting. Despite the encouraging results of this review, routine prophylaxis in ambulatory cancer patients cannot be recommended before safety issues are adequately addressed.

Primary prophylaxis for venous thromboembolism in patients undergoing cardiac or thoracic surgery.

BACKGROUND Cardiac and thoracic surgery are associated with an increased risk of venous thromboembolism (VTE). The safety and efficacy of primary thromboprophylaxis in patients undergoing these types of surgery is uncertain. OBJECTIVES To assess the effects of primary thromboprophylaxis on the incidence of symptomatic VTE and major bleeding in patients undergoing cardiac or thoracic surgery. SEARCH METHODS The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2014) and CENTRAL (2014, Issue 4). The authors searched the reference lists of relevant studies, conference proceedings, and clinical trial registries. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs comparing any oral or parenteral anticoagulant or mechanical intervention to no intervention or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS We extracted data on methodological quality, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS We identified 12 RCTs and one quasi-RCT (6923 participants), six for cardiac surgery (3359 participants) and seven for thoracic surgery (3564 participants). No study evaluated fondaparinux, the new oral direct thrombin, direct factor Xa inhibitors, or caval filters. All studies had major study design flaws and most lacked a placebo or no treatment control group. We typically graded the quality of the overall body of evidence for the various outcomes and comparisons as low, due to imprecise estimates of effect and risk of bias. We could not pool data because of the different comparisons and the lack of data. In cardiac surgery, 71 symptomatic VTEs occurred in 3040 participants from four studies. In a study of 2551 participants, representing 85% of the review population in cardiac surgery, the combination of unfractionated heparin with pneumatic compression stockings was associated with a 61% reduction of symptomatic VTE compared to unfractionated heparin alone (1.5% versus 4.0%; risk ratio (RR) 0.39; 95% confidence interval (CI) 0.23 to 0.64). Major bleeding was only reported in one study, which found a higher incidence with vitamin K antagonists compared to platelet inhibitors (11.3% versus 1.6%, RR 7.06; 95% CI 1.64 to 30.40). In thoracic surgery, 15 symptomatic VTEs occurred in 2890 participants from six studies. In the largest study evaluating unfractionated heparin versus an inactive control the rates of symptomatic VTE were 0.7% versus 0%, respectively, giving a RR of 6.71 (95% CI 0.40 to 112.65). There was insufficient evidence to determine if there was a difference in the risk of major bleeding from two studies evaluating fixed-dose versus weight-adjusted low molecular weight heparin (2.7% versus 8.1%, RR 0.33; 95% CI 0.07 to 1.60) and unfractionated heparin versus low molecular weight heparin (6% and 4%, RR 1.50; 95% CI 0.26 to 8.60). AUTHORS' CONCLUSIONS The evidence regarding the efficacy and safety of thromboprophylaxis in cardiac and thoracic surgery is limited. Data for important outcomes such as pulmonary embolism or major bleeding were often lacking. Given the uncertainties around the benefit-to-risk balance, no conclusions can be drawn and a case-by-case risk evaluation of VTE and bleeding remains preferable.