Very long half‐life plasminogen activator inhibitor type 1 reduces bleeding in a mouse model

OBJECTIVE

To investigate the potential for the future clinical use of a very long half‐life plasminogen activator inhibitor type 1 (VLHL PAI‐1) as a haemostatic agent.

MATERIALS AND METHODS

We developed a VLHL PAI‐1 (half‐life >700 h) recombinant mutant of PAI‐1 and assessed VLHL PAI‐1 for its ability to inhibit fibrinolysis in vitro using human, rabbit, mouse and rat blood. Fibrin clot lysis time, monitored by thromboelastometry, was determined at various concentrations of VLHL PAI‐1. Also, we determined total bleeding time and total blood loss of control, VLHL PAI‐1‐, tissue‐type plasminogen activator (tPA)‐ and tPA + VLHL PAI‐1‐treated mice.

RESULTS

Using a thromboelastometer, mouse blood was most similar to human blood in its coagulation and fibrinolytic characteristics. We evaluated the affect of VLHL PAI‐1 on haemostasis using the mouse model and showed that VLHL PAI‐1 is an effective inhibitor of fibrin clot degradation. It reduced time of bleeding and total blood loss.

CONCLUSION

VLHL PAI‐1 may provide an important physiological mechanism to protect clots from premature dissolution in surgical and trauma settings.     

Intraoperative acquisition of three-dimensional imaging for frameless stereotactic guidance during transsphenoidal pituitary surgery using the Arcadis Orbic System

OBJECT: Intraoperative fluoroscopy has long been used for anatomical localization in transsphenoidal pituitary surgery. More recently, frameless stereotaxy has been used to supplement 2D sagittal radiographs with 3D multiplanar reconstructions. Use of Arcadis Orbic allows both conventional fluoroscopic views and multiplanar reconstructions to be acquired intraoperatively without need for preoperative planning studies. The authors report their initial experience using Arcadis Orbic during transsphenoidal pituitary surgery. METHODS: To test the system, the authors placed a dehydrated human skull in a radiolucent head holder, and obtained standard 2D fluoroscopic images of the skull base and sella turcica. Arcadis Orbic was then used with frameless stereotaxy to register 3D multiplanar reconstructed images of skull base anatomy. The authors then used Arcadis Orbic in 26 transsphenoidal pituitary tumor resections and compared image quality, accuracy, and ease-of-use to standard techniques. Results: Arcadis Orbic 2D fluoroscopic images matched or exceeded the quality of images acquired by standard C-arm machines. Arcadis Orbic multiplanar reconstructions provided excellent images of the skull base when compared with preoperative Stealth computed tomography (CT) studies. Intraoperative frameless stereotactic navigation using Arcadis Orbic was highly accurate and more reliable than registering preoperative CT images. CONCLUSIONS: Arcadis Orbic provides excellent quality 2- and 3D images during transsphenoidal pituitary surgery, and intraoperative frameless navigation using these images is highly accurate. Arcadis Orbic is easy to use, even in patients with large body habitus, and image acquisition takes no longer than registration during a frameless stereotactic case. Based upon our preliminary experience, Arcadis Orbic precludes the need for preoperative CT studies in patients with pituitary lesions requiring frameless stereotactic navigation.     

Phacofragmentation with perfluorocarbon liquid and anterior chamber or scleral-fixated intraocular lens implantation for the management of luxated crystalline lenses--long-term results

PURPOSE: Estimation of long-term results and complications of complex surgical technique, used for the management of luxated crystalline lenses. MATERIAL AND METHODS: This prospective study involved 29 consecutive patients (31 eyes) with the mean age of 62 years. The applied surgical technique comprised pars plana vitrectomy, perfluorocarbon liquid injection and crystalline lens phacofragmentation in the vitreous cavity. Simultaneously, anterior chamber intraocular lenses (IOLs) were implanted in 13 eyes, and scleral-fixated, posterior chamber IOLs in 17 eyes. In one patient with high myopia the lens was not implanted. The follow-up ranged between 9 and 38 months (mean 22.8 months). RESULTS: No complications were observed during phacofragmentation. Improvement in visual acuity was achieved in 18 cases one week after operation and in 23 patients at last examination. We achieved visual acuity of 4/50--hand movements in 4 cases, 5/16-5/50 in 3 eyes, 5/8-5/12 in 7 and 5/5-5/7 in 17 cases, in last examination. There were no intra-operative complications. Low visual acuity in some cases was due to the presence of postoperative complications or coexisting eye diseases, such as secondary glaucoma, atonic pupil, age related macular degeneration, retinal detachment and macular hole. CONCLUSIONS: Phacofragmentation with perfluorocarbon liquid and IOL implantation for the management of luxated crystalline lenses is safe and effective method, providing very good long-term functional results.     

Transpupillary thermotherapy in exudative age-related macular degeneration

PURPOSE: Assessment of TTT results in patients with exudative age-related macular degeneration. MATERIAL AND METHODS: The study comprised of 65 patients (73 eyes), in age 50-84 years (average age-75 yrs). The diagnosis of exudative AMD was established on the basis of fundus examination and fluorescein angiography (FA) and in some cases on indocyanine green angiography. The baseline visual acuity (VA) ranged from counting fingers at 50 cm to 0.8. In 31 (42.5%) eyes occult CNV, in 11 (15%) minimally classic CNV and in 31 (42.5%) eyes predominantly classic CNV were observed. Subfoveal CNV was present in 70 (95.9%) eyes and perifoveal in 3 (4.1%). TTT was delivered using a diode laser at 810 nm wavelength, a spot size of 1.2 to 4.5 mm and a duration of 60 seconds for each spot with power settings between 320-800 mW. Follow-up examinations were carried out every 10-12 weeks. In cases with persistent leakage from CNV in late frames of FA a retreatment was performed. The follow-up period ranged from 6 to 28 months (average - 9.8 months). RESULTS: Visual acuity improved in 22 (30.1%) eyes, stabilized in 34 (46.6%) and deteriorated in 17 (23.3%). Fluorescein angiography showed no CNV leakage in 58 (79.5%) eyes. In 56 (71.8%) with regression of leakage in fluorescein angiography improvement or stabilization of visual acuity was detected. Subretinal haemorrhages after TTT were observed in 4 eyes (5.5%). At the end of the follow-up period fibrosis of CNV was detected in 12 eyes (16.4%). CONCLUSIONS: TTT is effective and safe method of treatment of occult and classic CNV in a course of wet AMD. In a majority of cases TTT results in total or partial regression of CNV and stabilization of visual acuity.     

Helicoidal peripapillary chorioretinal degeneration (HCPD)

Helicoidal peripapillary chorioretinal degeneration (HCPD) is characterized by bilateral wing- shaped atrophic areas in retina, radiating from the optic disc. Two cases (women: 23 and 58 years old) of this rare degeneration are presented. No changes of eye fundus and erg, eog, visual field evaluations had been noticed during 2 years follow-up.     

Lipoprotein (a) in patients with psoriasis: associations with lipid profiles and disease severity

Background  Lipoprotein (a) [Lp(a)] is a genetically determined molecule whose role has been implied in cardiovascular pathology, and whose levels have been reported to be elevated in patients with psoriasis.
Aim  To assess the serum levels of Lp(a) in patients with psoriasis, and to investigate the associations of Lp(a) with other lipids and with psoriasis severity.
Methods  Thirty-four patients with psoriasis and 26 healthy control subjects took part in the study. Serum levels of Lp(a) and total, high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) cholesterol fractions were measured in all participants. The levels of triglycerides and total cholesterol were measured using enzymatic colorimetric tests; HDL and LDL cholesterol concentrations were determined by precipitation methods; the VLDL concentration was calculated according to the formula: VLDL cholesterol = triglycerides/5.
Results  Patients with psoriasis showed significantly higher serum levels of Lp(a) relative to controls. Even when controlling for normolipidemic vs. hyperlipidemic status, abnormal levels of Lp(a) (> 30 mg/dL) were observed significantly more often in patients than in controls. In both patients and controls, Lp(a) levels correlated positively with total and HDL cholesterol levels. In patients, Lp(a) levels correlated positively with psoriasis severity.
Conclusions  Lp(a) may be a factor contributing to an increased cardiovascular risk in patients with psoriasis. A pathogenetic link may exist between this lipoprotein and psoriatic pathophysiology.     

Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study

Background and aimsCholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM.Methods and results57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA.A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP.ConclusionExogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.     

Multivariate analysis of risk factors for development of duodenal ulcer in Helicobacter pylori-infected patients

BACKGROUND: Although Helicobacter pylori is a significant etiologic factor of peptic ulcer disease, it remains unknown why ulcers develop only in the minority of infected individuals. AIM: The aim of this cross-sectional study was to evaluate the association between the presence of duodenal ulcer in H. pylori-infected patients and different risk factors. METHODS: A total of 122 H. pylori-infected patients were enrolled; 79 had duodenal ulcer and 43 gastritis. Univariate analysis was conducted using either Fisher's exact test or exact Cochrane-Armitage trend test. In multivariate analysis the logistic model was used. RESULTS: Univariate analysis indicated six factors (male sex, smoking, antral H. pylori density, CAGA presence in antrum, and VACA s1a presence in antrum and corpus). Four factors (sex, smoking-alcohol index, H. pylori density index, and CAGA index) were found to be significant in multivariate analysis. The best model predicting duodenal ulcer included male sex, smoking, presence of H. PYLORI on histopathology in antrum and CAGA presence in corpus. CONCLUSION: Although several risk factors were significantly associated with duodenal ulcer, we failed in the identification of either a single risk factor or a set of factors that can unequivocally differentiate patients with ulcer from those with gastritis.