Local Delivery of Antithrombotic Drug Inhibits Neointimal Hyperplasia Following Arterial Injury

The efficacy of local delivery of antithrombotic drugs on neointimal hyperplasia was investigated in 41 rabbits. One side of a rabbit iliac artery was injured by a balloon catheter as a control-injured artery. Another side of the iliac artery was also injured, and followed by local delivery of the antithrombotic drug (argatroban: 0.05 mg/kg; heparin 25 U/kg; or batroxobin 1 U/kg + heparin 25 U/kg). One hour after the balloon injury, angioscopy demonstrated occlusive or mural thrombus in all the controls, but few in the local drug-delivery arteries. Four weeks after balloon injury, angiographic percent stenosis in the locally drug-delivered arteries was 8%± 2% in the argatroban group (n = 7. P < 0.001 vs control side; 67%± 33%), 25%± 19% in the heparin group (n = 5, P < 0.005 vs control 66%± 14%), and 5%± 5% in the batroxobin group (n = 7, P < 0.01 vs control 59%± 39%). The activated partial thromboplastin time and fibrinogen did not change significantly. The PDGF-B chain was prominent at the neointimal layer in all the controls, but less so in the locally drug-delivered arteries. Thus, local delivery of antithrombotic drugs can inhibit neointimal hyperplasia after balloon injury by reducing thrombus related growth stimulation.     

Acidosis and raised norepinephrine levels are associated with exercise dyspnoea in idiopathic pulmonary fibrosis

Background and objective:   Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).
Methods:   Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.
Results:   Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO₂ and plasma NE occurred in the late exercise phase after the 'break point'. Compared with controls, patients with IPF had significantly higher HCO₃^- levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (ΔBorg scale/Δminute ventilation) correlated with the pH slope (ΔpH/Δoxygen uptake) (before the break point: r  = −0.537, P  = 0.0022; r  = −0.886, P  < 0.0001, after the break point) and the NE slope (ΔNE/Δoxygen uptake) (before the break point: r  = 0.481, P  = 0.0075; R  = 0.784, P  < 0.0001, after the break point).
Conclusions:   In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.     

Efficacy of Ramelteon in Patients with Insomnia and Nocturia

Objectives: To study the efficacy of ramelteon for patients with insomnia and nocturia. Methods: Forty‐nine patients experiencing insomnia and two or more nocturnal voids were included. The degree of lower urinary tract symptoms and sleep disorders was evaluated using the International Prostate Symptom Score (IPSS), Pittsburg Sleep Quality Index (PSQI) 1 score, and frequency/volume chart (FVC). The patients were treated with ramelteon (8 mg) for four weeks and then reexamined by questionnaire and FVC to evaluate the therapeutic efficacies. Results: The mean IPSS score was 16.1 ± 6.9 at baseline and 12.4 ± 7.1 at four weeks. The subject scores for the number of nocturnal voids also decreased significantly from 3.3 ± 0.9 to 2.9 ± 1.0. In addition, PSQI scores improved significantly from 7.4 ± 2.9 to 5.4 ± 2.8. According to the FVC, the number of nocturnal voids decreased significantly from 3.1 ± 1.2 at baseline to 2.2 ± 1.1 at four weeks, and nighttime bladder capacity improved significantly from 181.4 ± 79.9 to 201.1 ± 93.7 mL. Conclusion: Ramelteon alleviated nocturia and disturbed sleep in patients with insomnia and nocturia and led to increased nighttime bladder capacity.     

T-cell-dependent eosinophilia in the cerebrospinal fluid of the mouse infected with Angiostrongylus cantonensis

Eosinophilia of the cerebrospinal fluid (CSF) in permissive (rats) and non-permissive (mice) hosts infected with Angiostrongylus cantonensis, and the possible mechanism of the eosinophilia were studied. In three strains of thymic mice (ICR, ddY and BALB/c), the infection provoked a marked CSF eosinophilia starting at around day 12, reaching a peak level at day 20 and maintaining significantly high levels until day 35. In contrast, in athymic nude mice of BALB/c strain the infection failed to evoke this eosinophilia, suggesting T-cell dependence of murine CSF eosinophilia. Humoral antibodies did not correlate with the induction of eosinophilia. A time-course study of worm recovery in the mouse brains indicated a gradual but consistent reduction in worm burden in accordance with the rapid rise in CSF eosinophil levels. Bone marrow eosinophilia occurred in mice at day 5, which preceded CSF eosinophilia. Jirds, a permissive but less susceptible host, developed a CSF eosinophilia with a peak level at day 17, but which declined rapidly following the peak. Permissive rat hosts developed significant peripheral and bone marrow eosinophilia at day 35 but their CSF eosinophilia was markedly less prominent than that of mice and jirds. These data clearly indicate that there are distinct differences in the mechanism of eosinophilia and eosinophilia-inducing factors between permissive and non-permissive hosts.     

Role of sildenafil citrate in treatment of erectile dysfunction after radical retropubic prostatectomy

BACKGROUND: Sildenafil citrate was introduced as a treatment for erectile dysfunction in April 1998 in the United States and has been available since March 1999 in Japan. In this article, we assess the efficacy of sildenafil in the treatment of erectile dysfunction in Japanese men after radical retropubic prostatectomy for localized prostate cancer. METHODS: Of 106 men who underwent radical retropubic prostatectomy between January 1994 and March 2000, 43 were prescribed sildenafil at their request after radical retropubic prostatectomy. Medication was initiated at 25 mg, and if this was ineffective, the dose was increased to 50 mg. Of the patients, 18 underwent bilateral and 21 unilateral nerve sparing (NS) procedures, while in 4 patients, a non-NS procedure was performed. These patients were interviewed using a questionnaire about their response to sildenafil and using the 5-item International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: Thirty-three of the 43 patients were eligible for evaluation of the efficacy of sildenafil and 27 completed the IIEF-5 questionnaires. Sildenafil at 50 mg had a better effect on sexual function than 25 mg in most Japanese patients. Of the 16 patients who underwent bilateral NS procedures, 10 (62.5%) had improved ability for intercourse and 3 (18.8%) had improved erections. Of the 13 patients who underwent unilateral NS procedures, 7 (53.8%) had improved ability for intercourse and 4 (30.8%) had improved erections. None of the 4 patients who underwent non-NS procedures had a positive response. Of 24 patients with positive response to sildenafil, 3 (12.5%) did not have to take sildenafil after receiving it because they did not require it for intercourse. Mean IIEF-5 score increased from 4.3 to 11.4 (P < 0.0001). Patient age, time since surgery, PSA and pathological stage did not have statistically significant effects on outcome. The most commonly cited adverse effect was headache (21%). CONCLUSION: Sildenafil is equally effective for erectile dysfunction in Japanese patients who have undergone bilateral and unilateral NS procedures, and aids recovery of natural erectile function after radical retropubic prostatectomy. However, non-NS procedure patients had no response to sildenafil. This study suggested that sildenafil is well tolerated and should be initially used for treatment of Japanese men with erectile dysfunction after radical retropubic prostatectomy.