Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial

A multicenter, randomized placebo-controlled double-blind trial of nimodipine in poor-grade aneurysm patients was carried out in 17 Canadian hospitals. Of 188 patients enrolled in the trial, 32 were excluded for protocol violations and two were excluded due to statistical considerations, leaving 154 patients for valid outcome analysis. Nimodipine treatment was associated with a significantly better outcome (p less than 0.001): 21 (29.2%) of 72 nimodipine-treated patients had a good outcome at 3 months after subarachnoid hemorrhage (SAH) compared to eight (9.8%) of 82 placebo-treated patients. Delayed ischemic deficits from vasospasm alone were significantly less frequent in the nimodipine group (p less than 0.05) with permanent deficits occurring in five nimodipine-treated patients (6.9%) and in 22 placebo-treated patients (26.8%). Improvement in the good outcome rate and reduction in delayed ischemic deficits from vasospasm alone occurred in both Grade 3 and 4 patients, with no difference between nimodipine- and placebo-treated patients being found in Grade 5 patients. Repeat angiography after Day 4 was carried out in 124 patients. There was no significant difference in the incidence of moderate or severe diffuse spasm, which was seen in 64.3% of nimodipine-treated patients and 66.2% of placebo-treated patients. The authors conclude that nimodipine treatment in poor-grade patients with SAH results in an increase in the number of good outcomes and a reduction in the incidence of delayed neurological deterioration due to vasospasm. This effect occurs by a mechanism other than prevention of large-vessel spasm as visualized on angiography.     

变形链球菌表面蛋白和葡糖基转移酶基因疫苗对唾液变形链球菌和牙菌斑的影响

目的　了解变形链球菌表面蛋白和葡糖基转移酶基因疫苗单独及联合免疫对定菌鼠唾液变链菌和牙面菌斑的影响。方法　 2 8d龄 Wistar大鼠 3 6只 ,随机分为 pc DNA3 - pac组、pc DNA3 - gtf B组、pc DNA3 - pac联合pc DNA 3 - gtf B组、变形链球菌灭活全菌组、pc DNA3空载体组和 PBS液组 ,进行三次双侧颌下腺腺周注射免疫 ,建立定菌鼠模型 ,作诱龋实验 3个月。唾液变链菌计数和菌斑计分。结果　唾液变链菌菌落计数和牙面菌斑计分在 pc D-NA3与 PBS组最高 ,其次为单基因疫苗免疫组 ,联合基因疫苗和灭活全菌细胞免疫组最低 ,各组间有显著性差异 ( P<0 .0 5 )。结论　 pc DNA3 - gtf B和 pc DNA3 - pac具有明显的免疫抑菌作用 ,联合基因疫苗免疫优于单基因疫苗     

Effect of captopril on functional mitral regurgitation in dilated heart failure: a randomised double blind placebo controlled trial.

OBJECTIVE--To determine the efficacy and dose requirements of captopril to reduce functional mitral regurgitation in patients with dilated heart failure. DESIGN--A randomised double blind placebo controlled parallel arm trial. Incremental daily doses of 25 mg, 50 mg and 100 mg captopril used for a four week period each for a total of 12 weeks preceded by a two week placebo washout. Twenty eight ambulatory patients (mean age 72) New York Heart Association (NYHA) class II or III with apparently controlled ischaemic dilated heart failure (ejection fraction 29% (0.04%)) on digoxin, diuretics, and nitrates were randomised. All had at least grade 2/4 functional mitral regurgitation (> 5 cm2 regurgitant area on colour flow Doppler). RESULTS--Twenty three patients completed the study (13 on placebo and 10 on captopril). Significant improvements were confined to the captopril group. Compared with placebo the following improvements were noted in the captopril treated group: mitral regurgitant area decreased from a threshold at 50 mg/day (p < 0.05, mean (95% confidence interval (95% CI)) 3.1 (0.2 to 6.0) cm2), with a further decrease at 100 mg/day (p < 0.01, mean (95% CI) 5.3 (3.1 to 7.5) cm2). Significant improvements in all the other measurements were noted only after 100 mg/day. Stroke volume increased (p < 0.01, mean (95% CI) 11, (1.4 to 21) ml), systemic vascular resistance decreased (p < 0.05, mean (95% CI) 414 (35 to 793) dyn s cm5), left atrial area decreased (p < 0.05, mean (95% CI) 4.3 (0.03 to 8.6) cm2), and deceleration time increased (p < 0.01, mean (95% CI) 52 ms (7 to 98) ms). Left ventricular diameter decreased marginally (p = 0.06, mean (95% CI) 4 (-0.05 to 9 mm). Duke activity index score increased (p < 0.001, median (95% CI) 6.8 (4.5 to 12) points). Heart rate, mean arterial blood pressure, serum creatinine, and serum potassium did not change with either placebo or captopril. No patient was withdrawn directly due to the side effects of captopril. In an open phase nine placebo patients given captopril in rapid increments reaching 100 mg/day in the fourth week showed similar improvements. CONCLUSION--Captopril is efficacious in reducing functional mitral regurgitation in dilated heart failure. Patients require and must tolerate high doses (50-100 mg/day) for additive effects over supervised conventional treatment to occur.     

Cell survival characteristics of a human colon adenocarcinoma cell line after photodynamic treatment: a comparison of Photofrin II and TPPS

A comparison has been made of the in vitro light-activated drug cytotoxicities of two different porphyrin compounds, Photofrin II and TPPS4. An early passage human colon adenocarcinoma cell line, WiDr, has been exposed to either drug for 24 h, the excess drug washed from the cells and the cells irradiated with light using quartz-tungsten-halogen lamps. Neither light nor drug alone under the experimental conditions employed was toxic to WiDr cells. Together, considerable cytotoxicity could be seen and the shapes of the cell survival curves following exposure to either drug then irradiation with light, were similar. For equal amounts of drug in the medium, Photofrin II was a more efficient photosensitizer of WiDr cells than TPPS4, and differences in cellular uptake could only partly explain this. When the experimental procedure was changed by reducing the temperature of irradiation, a reduction in photosensitizing efficiency could be demonstrated. This was more pronounced for Photofrin II, and was seen as a change in the slope of the final portion of the survival curve; and as a change in the shoulder for TPPS4. Two different batches of the two drugs were compared and shown to give slightly different results for Photofrin II (change in shoulder) but not to differ for TPPS4.     

Effects of external pH on ionic currents in smooth muscle cells from the basilar artery of the guinea pig.

pHo is an important determinant of vascular tone in cerebral blood vessels. We investigated the effects of changes in pHo on isolated smooth muscle cells from the basilar artery of the guinea pig. Single cells contracted rapidly in response to an elevation in pHo (constant CO2), and contraction was blocked by nifedipine, suggesting a role for dihydropyridine-sensitive Ca2+ channels. In whole-cell patch-clamp experiments, changes in pHo (pHo 5.7-8.1, pHi 7.2 with 10 mM HEPES) strongly affected the amplitude of the peak Ca2+ channel current (10 mM Ba2+, +15 mV, holding potential of -55 mV), with an apparent pK of 6.9. The current-voltage curves were minimally shifted, indicating no important effect of surface charge. To separate the slowly inactivating L-type Ca2+ channel current from the more rapidly inactivating B-type current, the decaying portions of inward currents from cells studied with repetitive 1-second pulses (+15 mV, holding potential of -55 mV) were fit to a two-component model. Titration curves for the L-type and B-type currents indicated maximum increases by factors of 3.65 and 1.28 at alkaline pHo and gave apparent pK values of 7.71 and 6.47 (Hill coefficient unity). The time constant of inactivation for the B-type current at +15 mV was little affected by pHo, whereas that for the L-type current increased somewhat with increasing pHo. Additional experiments showed no significant effect of pHo on holding current or on voltage-activated outward currents (pCai 7 with 11 mM EGTA). Our results provide additional evidence for participation of Ca2+ channels in regulating basal tone in cerebral smooth muscle and indicate that pHo regulates current through slowly inactivating, dihydropyridine-sensitive L-type Ca2+ channels.     

Randomized clinical trial of tacrolimus- vs cyclosporine-based immunosuppression in pediatric heart transplantation: preliminary results at 15-month follow-up.

BACKGROUND: While Tacrolimus (Tac) and Cyclosporine (Cya) immunosuppression are used after cardiac transplantation (tx), few studies have evaluated their use in pediatric patients. METHODS: We randomized 26 heart transplant recipients (pts) in a prospective, open-label trial to Tac (n = 14) or Cya (n = 12) to compare their efficacy and side-effects. Mean age at tx was 4.2 years for Tac and 5.8 years for Cya. Mean follow-up was 26 months (range: 11-39 months) for Tac and 24 months for Cya (range: 33-13 months). RESULTS: Our data suggest that both regimens are efficacious in the pediatric population. Conversion from Cya to Tac was useful for dealing with persistent rejection, although this sample did not suggest lower incidence of acute cellular rejection in the Tac group. CONCLUSIONS: Further studies are required to establish pharmacokinetic parameters to enhance therapeutic monitoring of these patients to minimize side effects and enhance outcomes.     

On the Use of Paramagnetic Beads and Ferrofluids to Assess and Eliminate the Leukocytic Contribution to Oxygen Radical Generation by Human Sperm Suspensions

PROBLEM: To develop a methodology to determine a) the leukocytic contribution to reactive oxygen species generation by human sperm suspensions and b) the therapeutic value of removing these cellular contaminants. METHODS: Leukocytes were removed with paramagnetic beads or colloidal ferrofluids coated with anti-CD45 antibody. The sperm suspensions were monitored for oxidant generation by chemiluminescence, leukocyte contamination by immunocytochemistry, and fertilizing potential using zona-free hamster oocytes. RESULTS: Percoll®-prepared human sperm suspensions exhibited a competence for PMA-induced reactive oxygen species generation which was significantly correlated with leukocyte contamination. However, the purified spermatozoa remaining after paramagnetic bead treatment, also demonstrated an intrinsic capacity for PMA-responsive reactive oxygen species generation and, freed from the oxidative stress created by the leukocytes, exhibited a significantly enhanced capacity for sperm-oocyte fusion. CONCLUSIONS: Although human spermatozoa can generate reactive oxygen species, sperm function is inhibited by the additional oxidative stress created by contaminating leukocytes. Removal of these cells with paramagnetic beads enhances fertilizing potential.     

The characterization and pathological significance of gastric Campylobacter-like organisms in the ferret: a model for chronic gastritis?

Gastric campylobacter-like organisms (CLO) were isolated from gastric tissues removed at sacrifice from 17 mature ferrets; all animals were colonized, but no macroscopic mucosal lesions or histological features of chronic gastritis were seen. The isolates resembled Campylobacter pylori in many cultural and biochemical characteristics, and produced substantial urease activity, but there were sufficient differences from C. pylori to suggest that ferret gastric CLO represents a separate species. Comparison of human C. pylori and ferret gastric CLO may help to elucidate the pathogenicity of the former in patients with gastritis, and the ferret may serve as a useful animal model for the study of C. pylori infection.