Angiotensin-receptor blockers: revival of the systemic prevention of restenosis?

Restenosis following percutaneous coronary transluminal angioplasty and stenting remains a significant problem, occurring in 15–50% of patients within 6–9 months of the intervention. Several pharmacological approaches to reduce restenosis have been evaluated but to date none have been approved for this indication. Angiotensin II has been implicated in the development of restenosis through several physiologic mechanisms, and thus control of the renin-angiotensin system may be a potential target for its prevention. Although human trials have shown that angiotensin-converting enzyme inhibitors do not reduce the risk of restenosis, early data suggest that the selective AT₁ angiotensin receptor blocker valsartan may be effective in preventing in-stent restenosis in patients with complex lesions.     

Driving performance in patients with mild to moderate glaucomatous clinical vision changes

The purpose of this study was to determine the relationship between clinical measures of visual function and driving-related skills in patients with glaucoma who had good visual acuity in at least one eye and mild to moderate visual field loss. METHODS: Twenty-five patients with glaucoma and twenty-nine age-equivalent normally sighted control subjects were included in the study. We tested each patient on an interactive driving simulator and collected vision data, including Lighthouse visual acuity, Goldmann and Humphrey visual fields, and Pelli-Robson contrast sensitivity. Information about real-world accident history for the previous 5-year period was obtained. RESULTS: The glaucoma patients did not have significantly more simulator or real-world accidents than the normally sighted group. There were no significant differences between the groups in performance on seven of the eight simulator indexes that were measured. Of the clinical visual function measures, only lower contrast sensitivity in the eye with better contrast sensitivity correlated with driving skills, including slower speeds (r(24) = 0.58, p < or = 0.01), more lane boundary crossings (r(24) = -0.54, p < or = 0.01), and longer braking response times (r(24) = -0.60, p < or = 0.01) for the patient group. CONCLUSION: Reduced contrast sensitivity may be important in indicating the level of driving skills for individuals with glaucoma, who have normal or near-normal visual acuity and mild to moderate visual field loss.     

Functional independence of layer IV barrels

Our aim was to investigate the patterns of functional inputs and outputs from individual barrels in the mouse somatosensory cortex, and to test the hypothesis that individual barrels in layer IV are functionally independent of direct inputs from neighboring barrels. In a mouse in vitro slice preparation of the barrel cortex, we recorded voltage-sensitive dye signals evoked in response to microstimulation of a single barrel. Activity propagated from the stimulated barrel to the supragranular layers, where it spread to activate several barrel columns. However, in no instance did activity propagate directly from the stimulated barrel to neighboring barrels. Neither suppression of GABAergic inhibition, nor activation of N-methyl-D-aspartate receptors, revealed direct interbarrel interactions. By contrast, microstimulation in the supra- or infragranular layers resulted in direct propagation of activity to neighboring barrel columns. We conclude that the neurons within individual barrels are functionally independent of direct inputs from neighboring barrels. This suggests that the response properties of layer IV barrel neurons are shaped primarily by their presynaptic thalamic afferents and by intrabarrel interactions, and that these responses are independent of direct inputs from neighboring barrels.     

Comparison of contrast sensitivity,visual acuity,and Humphrey visual field testing in patients with glaucoma

BACKGROUND: Despite their normal or near-normal Snellen visual acuity, patients with glaucoma often complain of "poor" vision. OBJECTIVE: To investigate the relationship between large-letter contrast sensitivity, high-contrast visual acuity, and visual field defects in patients with glaucoma who have 20/40 or better visual acuity. DESIGN :Prospective, cross-sectional case series. PATIENTS AND METHODS: We evaluated 250 eyes of 144 subjects from the Glaucoma Service at the University of Illinois at Chicago College of Medicine. Subjects with a diagnosis of glaucoma, suspected glaucoma, or ocular hypertension who met the 20/40 or better vision requirement were recruited. Visual acuity was measured using the rear-illuminated Lighthouse Visual Acuity Chart at 4 m. Contrast sensitivity was measured using the Pelli-Robson Chart in a front-illuminated box with even luminance across the chart. Visual fields of the patients were measured using the 24-2 full-threshold program on the Humphrey Visual Field Analyzer. RESULTS: A significant correlation (r = 0.57, P < 0.001, n = 127) was found between the visual field mean deviations and the contrast sensitivity scores. The correlation (r = -0.322, P < 0.001, n = 127) was less between the visual field mean deviation and the log MAR visual acuity values, as was the correlation between the contrast sensitivity scores and log MAR visual acuity values (r = -0.370, P < 0.001, n = 127). In the subgroup of patients with chronic open-angle glaucoma, the correlation between the mean visual field deviation and the contrast sensitivity score was higher at 0.689 (P < or = 0.001, n = 62). CONCLUSIONS: Reduced contrast sensitivity is significantly correlated with visual field losses in patients with glaucoma and a visual acuity of 20/40 or better. The study data support the conclusion that, compared with visual acuity, the disease process preferentially affects contrast sensitivity. In our previous work, contrast sensitivity was shown to be more related than visual acuity to real-world function in patients with early glaucomatous changes.     

Estimate of the time zero lung burden of depleted uranium in Persian Gulf War veterans by the 24-hour urinary excretion and exponential decay analysis

The aim of this study was to estimate the amount of depleted uranium (DU) in the respiratory system of Allied Forces Gulf War Veterans. Mass spectrometry (thermal ionization mass spectrometry) analysis of 24-hour urinary excretion of DU isotopes in five positive (238U/235U > 191.00) and six negative (238U/235U > 138.25) veterans was utilized in the mathematical estimation of the pulmonary burden at the time of exposure. A minimum value for the biological half-life of ceramic DU oxide in the lungs was derived from the Battelle report of the minimum dissolution half-time in simulated interstitial lung fluid corresponding to 3.85 years. The average DU concentration was 3.27 x 10(-5) mg per 24 hours in DU-positive veterans and 1.46 x 10(-8) mg in DU-negative veterans. The estimated lung burden was 0.34 mg in the DU-positive and 0.00015 mg in the DU-negative veterans. Our results provide evidence that the pulmonary concentration of DU at time zero can be quantitated as late as 9 years after inhalational exposure.     

Adenovirus-catheter compatibility increases gene expression after delivery to porcine myocardium

Endomyocardial injection of adenoviral gene vectors enables localized delivery to comprised myocardial tissue. However, many materials used in endomyocardial delivery catheters may not be compatible with adenoviral gene vectors. In this study, a series of catheter-based endocardial and epicardial (direct visualization) procedures were performed to assess catheter-adenovirus compatibility in an in vivo model. A standard Nitinol-stainless steel (Ni-SS) catheter was compared with a novel Stiletto catheter designed for improved biocompatibility. In 4 animals 40 endocardial injections of adenovirus encoding beta-galactosidase (beta-Gal) were performed with the 2 catheters. After sectioning of the hearts only 8 of 20 Ni-SS beta-Gal+ sites could be identified (40% retrieval) whereas 16 of the 20 Stiletto injection sites were identified (80%). Within these areas successful transfection was observed (12.2 +/- 4.0 beta-Gal+ cells/high-power field [HPF] in the Ni-SS group vs. 30.1 +/- 6.8 beta-Gal+ cells/HPF in the Stiletto group; p = 0.03). After epicardial delivery to distinct areas of the myocardium adenoviral delivery as assayed by beta-galactosidase protein activity was >21 +/- 16-fold (range, 5 to >43-fold) greater than after Stiletto delivery. In conclusion, this study highlights the importance of adenovirus-material compatibility in gene delivery to the myocardium. Efficiency was greater when using the catheter designed to enhance biocompatibility.     

Evidence That Emotional Maladjustment Is Worse in Men Than in Women with Psychogenic Nonepileptic Seizures

The purpose of this study is to examine the effects of gender on adjustment and cognition in patients with psychogenic nonepileptic seizures (NES) and on patients with epilepsy. We compared 57 women and 27 men, all at least 16 years old, with only NES as documented by long-term EEG-video monitor studies, to equal numbers of randomly selected women and men with only epileptic seizures. Variables examined included age, age of onset, education, scales from the MMPI, the WAIS-R, and the number of tests outside normal limits from the Neuropsychological Battery for Epilepsy. We found no significant differences in mean age, intelligence, or percentage of neuropsychological tests outside normal limits across the four groups. Women and men with NES had significantly later age of onset of attacks compared with subjects of either gender with epilepsy (26 years vs 13 years, P < 0.001) and men with NES had greater educational achievement than women with NES or patients with epilepsy (P < 0.02). However, the most important findings were seen on the MMPI. Men with NES exhibited significantly greater elevations on multiple scales (especially Hysteria, Depression, Hypochondriasis, Psychoasthenia, Schizophrenia) compared with men with epilepsy or women with either epilepsy or NES. We conclude that men with NES have significantly worse patterns of emotional adjustment, as measured by the MMPI, than women with NES or subjects of either gender with epilepsy.