Pneumatic retinopexy by evaporation of fluorocarbon liquids: in vitro and in vivo results

Purpose To develop an expanding gas tamponade allowing a controlled and complete filling of the vitreous cavity in the non-vitrectomized eye. Methods Twenty-two different liquid fluorocarbon mixtures with a high vapour pressure were tested in an in vitro eye model and in rabbit eyes. The intraocular pressure (IOP), the anterior segment of the eye, the vitreous and the retina were inspected at each examination during a period of 2 weeks. The timepoint of maximal gas expansion and the period required for complete absorption of the gas bubble were recorded. Results In vitro, admixtures of perfluorocarbons (PFCLs) and of semifluorinated alkanes (SFAs) with ether/alkanes generated limited temporary gas expansion but increased IOP. Admixtures of n-pentane in paraffin oil or silicone oil resulted in incomplete gas filling remaining for several days, with moderate IOP. In vivo, different clinical features and gas expansion were observed after the injection of PFCLs saturated with CO₂ or SF₆. Normal IOP was noted, but only with a transient and incomplete gas expansion and tamponade. For example, with n-pentane/n-hexane/perfluoromethylcyclopentane/perfluoromethyl-cyclohexane (1:1:1:1) a very rapid gas expansion was observed, followed by a raised IOP, a shallow anterior chamber, and finally rupture of the globe. The correlation between the in vitro and in vivo data was low. Conclusions Gas endotamponade based on evaporation of liquid fluorocarbons is possible, but a complete and reliable tamponade could not be achieved. The best results were demonstrated by admixtures with an overall density <1.00 g/cm³, an inert carrier with high vapour pressure, and a highly volatile substance. Further detailed investigation into the factors influencing evaporation is required.     

Intensity-modulated radiation therapy for prostate cancer: late morbidity and results on biochemical control.

PURPOSE: To report on late morbidity and biochemical relapse-free survival (bRFS) after intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS: Between 1998 and 2005 133 patients were treated with IMRT for T(1-4) N0 M0 prostate cancer. The median follow-up time was 36 months. In a first cohort, patients received a median planning target volume (PTV) dose of 74 Gy with a hard constraint on maximum rectum dose of 72 Gy (74R72, n=51). Later, median PTV and maximum rectum dose were increased to 76 and 74 Gy, respectively (76R74; n=82). We defined low-risk (n=20), intermediate-risk (n=70) and high-risk (n=43) groups. Androgen deprivation was given to patients in the intermediate- and high-risk group. Late gastro-intestinal (GI) and genito-urinary (GU) morbidity and biochemical relapse, in accordance with the ASTRO consensus, were recorded. RESULTS: We observed grade 2 GI (17%) and GU (19%), grade 3 GI (1%) and GU (3%) late toxicities. Except for hematuria, the median duration of side-effects was 6 months. Biochemical relapse-free survival (bRFS) at 3 and 5 years was 88% and 83%, respectively, with a significantly better 3-year bRSF for the 76R74 than for the 74R72 group (p=0.01). Five-year bRFS for patients in the low-risk, intermediate-risk and high-risk group was 100%, 94% and 74%, respectively (p<0.01). CONCLUSION: IMRT for localized or locally advanced prostate cancer combines low morbidity with excellent biochemical control.     

Tec regulates platelet activation by GPVI in the absence of Btk

The Tec family kinase Btk plays an important role in the regulation of phospholipase C gamma 2 (PLC gamma 2) downstream of the collagen receptor glycoprotein VI (GPVI) in human platelets. Platelets also express a second member of this family, Tec; however, its function has not been analyzed. To address the role of Tec, we analyzed Btk-/-, Tec-/-, and Btk/Tec double-deficient (Btk-/-/Tec-/-) platelets. Tec-/- platelets exhibit a minor reduction in aggregation to threshold concentrations of collagen or the GPVI-specific agonist collagen-related peptide (CRP), whereas responses to higher concentrations are normal. Tyrosine phosphorylation of PLC gamma 2 by collagen and CRP is not altered in Tec-/- platelets. However, Btk-/-/Tec-/- platelets exhibit a greater reduction in PLC gamma 2 phosphorylation than is seen in the absence of Btk, thus revealing an important role for Tec in this situation. Furthermore, Btk-/-/Tec-/- platelets fail to undergo an increase in Ca2+, aggregation, secretion, and spreading in response to collagen or CRP, whereas they aggregate normally to adenosine diphosphate (ADP) and spread on fibrinogen. A residual GPVI signal exists in the Btk-/-/Tec-/- platelets as CRP synergizes with ADP to mediate aggregation. These results demonstrate an essential requirement for Tec and Btk in platelet activation by GPVI and reveal a functional role for Tec in the regulation of PLC gamma 2 in the absence of Btk.     

Hemostatic markers with bolus versus prolonged heparin after carotid artery stenting

BACKGROUND: The evolving technique of carotid stenting (CS) requires optimal antithrombotic strategies to reduce periinterventional thromboembolic risk. In animal models of balloon injury, tissue factor (TF) was shown to be the major procoagulant of the atherosclerotic plaque mediating prolonged procoagulant activity. METHODS: We analyzed TF and TF-dependent hemostatic markers before and 2, 6 and 24 h after CS with two antithrombotic drug regimens. Group A (n=20) received prolonged unfractionated heparin (UFH) for 18-20 h starting at intervention next to aspirin and thienopyridine. In group B (n=16), single bolus UFH was administered next to combined antiplatelet therapy. Natural anticoagulants were determined at baseline. RESULTS: Patients with symptomatic and asymptomatic cerebrovascular disease did not differ in plasma TF levels. Furthermore, no statistically significant difference for TF, TFPI/Xa-complex and prothrombin fragment F1.2 was observed between bolus and prolonged heparin treatment. No significant change was found in time course for these parameters. Two patients (5.5%; one in each treatment group) suffered periinterventional minor stroke associated with increased levels of F1.2 and TFPI/Xa-complex. Both were resistant to activated protein C (APC ratio<1.9) due to heterozygous factor V Leiden mutation. CONCLUSIONS: No significant activation of the TF pathway was seen with both antithrombotic regimens suggesting that single bolus UFH combined with antiplatelet therapy is generally sufficient to control TF-dependent procoagulant activity after CS. However, patients with resistance to activated protein C may be at increased periinterventional stroke risk.     

Role of taurine accumulation in keratinocyte hydration

Epidermal keratinocytes are exposed to a low water concentration at the stratum corneum-stratum granulosum interface. When epithelial tissues are osmotically perturbed, cellular protection and cell volume regulation is mediated by accumulation of organic osmolytes such as taurine. Previous studies reported the presence of taurine in the epidermis of several animal species. Therefore, we analyzed human skin for the presence of the taurine transporter (TAUT) and studied the accumulation of taurine as one potential mechanism protecting epidermal keratinocytes from dehydration. According to our results, TAUT is expressed as a 69 kDa protein in human epidermis but not in the dermis. For the epidermis a gradient was evident with maximal levels of TAUT in the outermost granular keratinocyte layer and lower levels in the stratum spinosum. No TAUT was found in the basal layer or in the stratum corneum. Keratinocyte accumulation of taurine was induced by experimental induction of skin dryness via application of silica gel to human skin. Cultured human keratinocytes accumulated taurine in a concentration- and osmolarity-dependent manner. TAUT mRNA levels were increased after exposure of human keratinocytes to hyperosmotic culture medium, indicating osmosensitive TAUT mRNA expression as part of the adaptation of keratinocytes to hyperosmotic stress. Keratinocyte uptake of taurine was inhibited by beta-alanine but not by other osmolytes such as betaine, inositol, or sorbitol. Accumulation of taurine protected cultured human keratinocytes from both osmotically induced and ultraviolet-induced apoptosis. Our data indicate that taurine is an important epidermal osmolyte required to maintain keratinocyte hydration in a dry environment.