Circulating platelet aggregates and progression of visual field loss in glaucoma

The aim of the study was to assess a relationship between circulating platelet aggregates (CPA) and progression of visual field loss in primary open-angle glaucoma patients. CPA was determined in 27 patients with open-angle glaucoma with nonprogressive visual field loss and 15 patients with open-angle glaucoma and progression of visual field loss. Intraocular pressure (IOP) under topical therapy was < 18 mmHg in all patients. CPA in glaucoma patients with progression of visual field loss was not significantly higher than those without visual field progression (p = 0.59). In conclusion, our study shows that increased platelet aggregability is not solely responsible for progression of visual field loss in glaucoma patients, and indicates the role of IOP in the pathogenesis of visual field loss.     

Persistence, spatial distribution and implications for progression detection of blind parts of the visual field in glaucoma: a clinical cohort study

Background

Visual field testing is an essential part of glaucoma care. It is hampered by variability related to the disease itself, response errors and fatigue. In glaucoma, blind parts of the visual field contribute to the diagnosis but - once established – not to progression detection; they only increase testing time. The aims of this study were to describe the persistence and spatial distribution of blind test locations in standard automated perimetry in glaucoma and to explore how the omission of presumed blind test locations would affect progression detection.

Methodology/Principal Findings

Data from 221 eyes of 221 patients from a cohort study with the Humphrey Field Analyzer with 30–2 grid were used. Patients were stratified according to baseline mean deviation (MD) in six strata of 5 dB width each. For one, two, three and four consecutive <0 dB sensitivities in the same test location in a series of baseline tests, the median probabilities to observe <0 dB again in the concerning test location in a follow-up test were 76, 86, 88 and 90%, respectively. For <10 dB, the probabilities were 88, 95, 97 and 98%, respectively. Median (interquartile range) percentages of test locations with three consecutive <0 dB sensitivities were 0(0–0), 0(0–2), 4(0–9), 17(8–27), 27(20–40) and 60(50–70)% for the six MD strata. Similar percentages were found for a subset of test locations within 10 degree eccentricity (P>0.1 for all strata). Omitting test locations with three consecutive <0 dB sensitivities at baseline did not affect the performance of the MD-based Nonparametric Progression Analysis progression detection algorithm.

Conclusions/Significance

Test locations that have been shown to be reproducibly blind tend to display a reasonable blindness persistence and do no longer contribute to progression detection. There is no clinically useful universal MD cut-off value beyond which testing can be limited to 10 degree eccentricity.     

Numerical investigations of the haemodynamic changes associated with stent malapposition in an idealised coronary artery

The deployment of a coronary stent near complex lesions can sometimes lead to incomplete stent apposition (ISA), an undesirable side effect of coronary stent implantation. Three-dimensional computational fluid dynamics (CFD) calculations are performed on simplified stent models (with either square or circular cross-section struts) inside an idealised coronary artery to analyse the effect of different levels of ISA to the change in haemodynamics inside the artery. The clinical significance of ISA is reported using haemodynamic metrics like wall shear stress (WSS) and wall shear stress gradient (WSSG). A coronary stent with square cross-sectional strut shows different levels of reverse flow for malapposition distance (MD) between 0 mm and 0.12 mm. Chaotic blood flow is usually observed at late diastole and early systole for MD=0 mm and 0.12 mm but are suppressed for MD=0.06 mm. The struts with circular cross section delay the flow chaotic process as compared to square cross-sectional struts at the same MD and also reduce the level of fluctuations found in the flow field. However, further increase in MD can lead to chaotic flow not only at late diastole and early systole, but it also leads to chaotic flow at the end of systole. In all cases, WSS increases above the threshold value (0.5 Pa) as MD increases due to the diminishing reverse flow near the artery wall. Increasing MD also results in an elevated WSSG as flow becomes more chaotic, except for square struts at MD=0.06 mm.     

Comparison of visual evoked potentials, automated perimetry and frequency-doubling perimetry in early detection of glaucomatous visual field loss

The present study compares frequency-doubling perimetry (FDP), automated perimetry (AP) and visual evoked potentials (VEP) for their ability to diagnose early glaucoma. In present study 224 patients of Clinic for Eye Diseases, Clinical Hospital "Sestre Milosrdnice" that had diagnosis of open angle glaucoma and glaucomatous visual field loss proven by automated static perimetry on only one eye were performing all three tests. Visual evoked potentials, automated perimetry and frequency-doubling perimetry were performed four times in each patient with six months period in between testing. Significant difference was proven between frequency-doubling perimetry and automated perimetry in favor for FDP in early detection of glaucomatous field loss. There was no significant difference between FDP and VEP neither between VEP and AP measurements. The results of this study indicate that frequency-doubling perimetry is significantly better method for early detection of glaucomatous visual field loss than automated static perimetry.     

Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH

During atherogenesis, the extracellular pH of atherosclerotic lesions decreases. Here, we examined the effect of low, but physiologically plausible pH on aggregation of modified LDL, one of the key processes in atherogenesis. LDL was treated with SMase, and aggregation of the SMase-treated LDL was followed at pH 5.5-7.5. The lower the pH, the more extensive was the aggregation of identically prelipolyzed LDL particles. At pH 5.5-6.0, the aggregates were much larger (size >1 μm) than those formed at neutral pH (100-200 nm). SMase treatment was found to lead to a dramatic decrease in α-helix and concomitant increase in β-sheet structures of apoB-100. Particle aggregation was caused by interactions between newly exposed segments of apoB-100. LDL-derived lipid microemulsions lacking apoB-100 failed to form large aggregates. SMase-induced LDL aggregation could be blocked by lowering the incubation temperature to 15°C, which also inhibited the changes in the conformation of apoB-100, by proteolytic degradation of apoB-100 after SMase-treatment, and by HDL particles. Taken together, sphingomyelin hydrolysis induces exposure of protease-sensitive sites of apoB-100, whose interactions govern subsequent particle aggregation. The supersized LDL aggregates may contribute to the retention of LDL lipids in acidic areas of atherosclerosis-susceptible sites in the arterial intima.     

Role of thromboxane A2 and platelet activating factor in early haemodynamic response to lipopolysaccharide in rats.

The mechanism of early pulmonary and systemic haemodynamic response to intravenous infusion of LPS from Escherichia coli was investigated in anesthetised Wistar rats. 10 mg of LPS given at a rate of 4 mg/kg/min but not at a rate of 1 mg/kg/min induced an increase in pulmonary arterial pressure (PAP) and a fall in systemic arterial pressure (SAP). Pretreatment with a PAF receptor antagonist; WEB 2170 (5 and 25 mg/kg) inhibited both PAP and SAP responses to LPS (4 mg/kg/min) while an inhibitor of thromboxane synthesis; Camonagrel (10 and 20 mg/kg) abolished PAP response without a major effect on SAP response to LPS. In conclusion, both PAF and TXA2 mediate LPS induced rise in pulmonary arterial pressure while LPS-induced fall in systemic arterial pressure is mediated by PAF.     

Fahraeus-effect-reversal (FER) in compaction stasis (CS): microrheological and haemodynamic consequences of intravascular sedimentation of red cell aggregates

Red cell aggregate sedimentation under gravitation produces pronounced and rapid "phase separation effects" culminating in "compaction stasis" (CS), i.e. almost complete stuffing of microvessels by RBC. This can be readily observed and monitored in microvessels of vertically placed mesentery preparations by a horizontally aimed intravital microscope as shown by (GOBEL et al. VIRCHOW's Arch., 1988,). "Layered flow", floatational plasma skimming and progressive increase in local tube hematocrit (HT) up to 100% ("compaction stasis") occurs during induced low flow states in vivo (here preferentially in postcapillary venules), as well as in vitro (non-permeable artificial micro tube networks). Quantitative densitometry and velocimetry in vertically placed microvessels demonstrates that the process of RCA sedimentation results in progressive vertical skewing of the velocity profile, culminating in standstill of the RBC-sediment in the dependent vessel half, with superfluent plasma and small aggregates in the upper vessel half. The theory of compaction stasis is developed: in striking contrast to the situation under high shear conditions, red cells travel on slower trajectories than plasma: due to "red cell undervelocity" the average residence times of RBC in a venule is much higher than that of plasma. Consequently, CS can be explained as the result of a FAHRAEUS effect reversal since the principle of mass conservation requires that HT much greater than HD. Network aspects and hemodynamic consequences are also incorporated into the theory.     

Formation of field discontinuities and islands in visual cortical maps

The representations of visual hemifields in the extrastriate areas of various species exhibit field discontinuities and islands. We propose that these violations of retinotopy are a developmental consequence of the elongated shape of the respective cortical areas. To substantiate this claim, we investigated a model of activity-driven map formation. In agreement with observations, this model yields maps with field discontinuities if the cortical areas exceed a threshold elongation. Moreover, within the same model island representations in the periphery and the area centralis can also be understood. A multistability of the solutions in the model gives a very simple explanation for the observed interindividual variability of maps in cats. The model leads to a prediction of the radial dependence of the areal magnification factor near field discontinuities, which could be accessible for a high precision mapping experiment.     

Genetic changes in skin tumor progression: correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7

Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restriction fragment length polymorphisms at multiple chromosomal loci. Analysis of loss of heterozygosity in such tumors showed that imbalance of alleles on mouse chromosome 7, on which the H-ras gene is located, occurs very frequently in skin carcinomas. The chromosomal alterations detected, which included both nondisjunction and mitotic recombination events, were only seen in tumors that have activated ras genes. We conclude that gross chromosomal alterations that elevate the copy number of mutant H-ras and/or lead to loss of normal H-ras are a consistent feature of mouse skin tumor development.     

Assessment of haemodynamic changes and acid-base equilibrium during hypovolaemia and after infusion of plasma substitutes in dogs

The following haemodynamic values were determined in anaesthetized mongrel dogs: heart rate, systolic blood pressure in the ascending aorta, left ventricular pressure at the peak dp/dt, left ventricular end-diastolic pressure, time interval from Q in ECG to the onset of the systolic wave of dp/dt, time interval from Q in ECG to peak dp/dt, maximum rate of left ventricular pressure rise, femoral arterial flow, and certain indices of left ventricular contractility. It was concluded from the results of these experiments that infusion of a modified gelatin solution Fluigel prevented haemodynamic and metabolic changes produced by experimental hypovolaemia more effectively than infusion of Plasmagel.     

Importance and outlook of research in the field of human molecular genetics

We present a brief survey of the main results obtained in the studies of human molecular genetics. Principal attention is paid to the studies of normal genes and human genetic elements, to molecular genetics of inherited diseases, the use of DNA polymorphic regions for the analysis of genetic defects and to the development of genetic therapy methods. The survey presents both the main results obtained and most interesting data collected in this field by Soviet researchers.