Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma.

BACKGROUND: Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field. METHODS: In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. RESULTS: Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. CONCLUSION: Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine.     

Selective modification at the N-terminal region of human growth hormone that shows antagonistic activity

A new analogue of recombinant human growth hormone (hGH), hGH des(1–6,14) was expressed in Escherichia coli, refolded and purified to homogeneity. The mutation decreased the hormone's ability to bind lactogenic and somatogenic receptors through its site 1, and almost completely abolished its ability to bind these receptors through site 2, as evidenced by both binding and gel-filtration experiments. More specifically, the binding to prolactin receptors (PRLRs) from various species or their soluble recombinant extracellular domains (ECDs) was decreased 1.5–4-fold, whereas the binding to hGH receptor (hGHR) was decreased 10–85-fold. These changes caused an almost total loss of hormone agonistic activity in several in vitro bioassays and subsequently, the hGH des(1–6,14) analogue acquired antagonistic properties. This antagonistic activity was dependent upon modification of site 1. In those cases in which the binding was reduced only slightly, e.g. binding to rabbit PRLRs, hGH des(1–6,14) acted as a strong antagonist, whereas in others in which the binding of site 1 was reduced to a higher degree, such as other PRLRs and, in particular, hGHR, the antagonistic activity was correspondingly weaker. Circular dichroism spectra of the analogue suggested that these changes do not result from a decrease in overall -helix content, but rather from minor local structural modifications at the N-terminus.     

Percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease using a transluminal endatherectomy catheter (TEC): Initial results and angiographic follow-up

Purpose To evaluate the clinical results of percutaneous transluminal rotational atherectomy in the treatment of peripheral vascular disease. Methods Rotational atherectomy was performed in 39 patients aged 39–87 years (mean 66.6 years). A total of 71 lesions (43 stenoses and 28 occlusions) were treated in 40 limbs. Additional balloon angioplasty was required in 54% of lesions. Fifteen patients (37.5%) presented in Fontaine stage II, 10 patients (25%) in Fontaine stage III and 15 patients (37.5%) in Fontaine stage IV. Rotational atherectomy at 750 rpm was carried out over a 0.014-inch guidewire with continuous aspiration into a vacuum, bottle. Follow-up angiography and color flow Doppler examinations were performed in 22 patients (23 limbs) after a mean period of 6 months (range 2–14 months) Results There was one primary technical failure. In 36 of 40 lesions there was a good angiographic result with residual stenoses in less than 30%. In 70 lesions treated by rotational atherectomy, however, 54% showed residual stenoses of 30%–50% and these cases required additional balloon angioplasty. The mean ankle-brachial index improved significantly (p<0.001), from 0.49 before the procedure to 1.01 after the procedure. A single distal embolus, related to primary recanalization, occurred and there were two large inguinal hematomas. Cumulative clinical patency after 6 months was 83.8% and cumulative angiographic patency after 6 months was 79.1%. Conclusion Percutaneous rotational atherectomy is a promising approach for the treatment of chronic peripheral vascular disease. Further prospective, randomized studies are necessary to compare percutaneous transluminal angioplasty with this new technical approach.     

Decomposing Area of Residence Differences in Multiple Regression Studies: The Relative Contributions of Independent Variables and Model Coefficients

When rural/urban differences are found in health status or health care use, it is often desirable to identify those factors (such as age, social structure, income, etc.) that influence such differences. To this end, researchers often test rural/urban differences in age, social structure, income, etc., for statistical significance. Also, researchers commonly perform multivariate analyses (such as multiple regressions) to examine rural-urban differences in the influence of various independent variables on the dependent variable of interest. Frequently, researchers discover: (1) statistically significant rural/urban differences in the independent variables (such as age, social structure, income, etc.) and (2) statistically significant rural/urban differences in the effects of these independent variables (i.e., statistically significant rural/urban differences in regression coefficients). The analysis typically stops here, without addressing the relative contributions of (1) and (2) to the rural/urban differences in the dependent variable. This paper argues that the relative contributions of (1) and (2) have important implications for the way policy-makers address rural health problems. This paper presents a method for assessing the relative contributions of differences in the independent variables and differences in regression coefficients to observed differences in the dependent variable, and illustrates the application of the method by analyzing rural/urban differences in the risk of institutionalization.     

An analytical solution for the SSFP signal in MRI.

Among previous analyses of the steady-state free-precession (SSFP) signal in rapid MRI, one treatment resulted in equations that require the evaluation of infinite binomial series. Here, an analytical solution is derived by a transformation into the power series expansion of the derivative of the inverse sine function, which is essentially a root. The treatment is extended to include higher-order signals. The results demonstrate the identity of the vastly different equations for the SSFP signals reported so far. Applications consist of the derivation of closed expressions for the signal in echo-shifted MRI and a corresponding analysis of TrueFISP sequences.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute G_i/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca²⁺/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute μ-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of {ie195-2} subunits ({ie195-3} scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that {ie195-4} is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Effect of Ethanol and Stress on Plasma Catecholamines and Their Relation to Changes in Emotional State and Performance

The "tension reduction hypothesis" of ethanol was investigated with respect to stress- and ethanol-induced changes of plasma catecholamines and their relations to changes in emotional state and performance. Twenty-two healthy male volunteers were tested under the influence of 0.8 g/kg ethanol and compared to 22 matched controls receiving a placebo drink. Stress was induced by mental arithmetic applied prior to and 45 min after fluid consumption. Plasma epinephrine (E) and norepinephrine (NE) obtained from an indwelling cannula inserted 50 min prior to stress application were determined prior to and after each stress session. Percentage changes were compared within and between groups and correlated with respective changes of emotional states and performance in mental arithmetic. While ethanol decreased performance and stress-related emotional arousal, it did not affect stress-induced changes in plasma catecholamines. Rather, the fluid (ethanol as well as placebo) increased NE levels. Emotional tension reduction was associated with low resting or average levels of E in the placebo group but this relationship was disrupted by ethanol. High NE resting levels and drink induced increases predicted emotional tension reduction with placebo but an increase in stress induced depression with alcohol. "Biochemical tension reduction" (represented by both reduced E and NE stress response) may be predicted from generally lower levels of activation and elation by alcohol but not with the placebo condition. Although performance was positively related to low NE resting levels and stress responses, no influence of alcohol on this relationship was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ethanol on plasma amino acids and related compounds of stressed male rats

Plasma amino acid levels in rats are known to be affected by ethanol or by immobilization stress. This paper investigated the effect of ethanol on plasma amino acid levels of stressed rats. Rats received ethanol (2 g/kg, IP) 15 minutes prior to a 30-min immobilization period. Blood samples were obtained from individual rats before, during and after stress. Ethanol lowered the concentration of most plasma amino acids (AA) or related compounds in stressed rats (e.g., aspartic acid, threonine, serine, glycine, alanine, valine, tyrosine, phenylalanine, tryptophan). Some compounds remained unaffected (e.g., taurine, cystine, ethanolamine and methylhistidines) and one (phosphoethanolamine) increased initially. A comparison of the effects of ethanol on plasma AA and related compounds in resting and stressed rats shows similarities and differences. In general, ethanol tends to change the concentrations of these compounds away from normal levels in nonstressed rats, whereas in stressed rats, ethanol tends to antagonize stress-induced changes. This study shows that ethanol can affect individual AA and related compounds differently in nonstressed and stressed rats and that ethanol reduces stress-induced changes. The latter finding supports the "tension-reduction hypothesis" of ethanol.