Multi-modal treatment of primarily using continuous subcutaneous interferon-α injection in combination with surgery and/or radiotherapy

PURPOSE: Thirty-nine renal cell carcinoma patients with bony metastasis were intensively treated, primarily with immunotherapy using natural type interferon-alpha (IFN-alpha) continuous subcutaneous injection in combination with surgical resection and radiation therapy. Long-term survival was achieved, including three patients with complete response. The results of this study are presented. METHODS: The mode of administration of IFN-alpha was as follows: natural-type IFN-alpha (25,000,000 IU) was dissolved in 60 mL of distilled water and administered via continuous subcutaneous injection (0.5 mL/h) as 'one course of the treatment'. Two courses of IFN-alpha therapy were given 2 weeks preoperatively, while 13 courses of IFN-alpha therapy were given postoperatively (one course per week). Thus, 15 courses of IFN-alpha therapy were administered during the trial period. Thereafter, IFN-alpha therapy was repeated either every week or every other week depending on the condition of the patient. Additionally, blood levels of IFN-alpha were monitored for four patients following initiation of IFN-alpha continuous subcutaneous injection therapy. RESULTS: Immediately after injection of IFN-alpha, blood levels of IFN-alpha started to rise, reaching 40.5 IU/mL on average at 24 h after initiation of IFN-alpha therapy. Thereafter, blood levels of IFN-alpha remained high and measurable blood levels of IFN-alpha were maintained for up to 24 h after completion of IFN-alpha injection. As a whole, IFN-alpha was detectable for 6-8 days and Cmax (maximum blood concentration of IFN) was 167 IU/mL. Thirty-nine patients with bony metastases were treated as follows: IFN mono-therapy (19 patients), IFN and radiation therapy (15 patients) and IFN and surgical resection of bony metastases (five patients). Fourteen patients survived and the details of these 14 patients are as follows: complete response in three cases, partial response in two, no change in six and progressive disease in three. Twenty-five patients died of renal cell carcinoma. The overall 5-year survival rate was 35.0%. CONCLUSIONS: These findings indicate that IFN-alpha continuous subcutaneous injection therapy is a useful modality for renal cell carcinoma patients with bony metastasis if administered in combination of radical nephrectomy and radiation therapy.     

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.     

Production of Blocking Antibodies by Vaccination With Husband's Lymphocytes in Unexplained Recurrent Aborters: The Role in Successful Pregnancy

ABSTRACT: To elucidate an immunological mechanism in terms of the effectiveness of vaccination of the unexplained habitual aborters with their husband's lymphocytes, 20 patients were selected as the experimental group, and 10 fertile couples were selected as the control group. Subjects were studied by mixed lymphocyte reaction-blocking assay so as to determine whether they had blocking antibodies (BAbs) in their sera. In the experimental group, BAb levels were found to be significantly lower as compared to the ten control multiparous wives; 17 cases (85%) of them were proved not to have sufficient BAbs. Significant sharing of HLA-D/DR antigens was observed in experimental couples. Then, 10 out of 17 patients with evidence of no produced BAbs were vaccinated with their husband's lymphocytes, and all of them were observed to produce BAbs within three vaccinations. After vaccination, seven out of ten patients have so far become pregnant, five of these pregnancies have been successful, with evidence of continuing production of BAbs. In conclusion, vaccination of the patients with husband's lymphocytes was found to stimulate a production of BAbs, and it was thus strongly suggested that this may lead to their production in a subsequent pregnancy, which would allow its success.     

A longitudinal study of blood pressure,cholesterol and left ventricular muscle volume in children: The Shimane Heart Study

Three hundred and forty-four healthy schoolchildren living in Izumo City, Shimane Prefecture, Japan, were assessed at 3 year intervals from 6 to 15 years, starting in 1978 (Cohort 1) or 1981 (Cohort 2). Tracking indices (Ti) were calculated as follows: Ti = (2x + y - z)/N/0.89, where x, y and z refer to the total number in the same, adjacent and remote trisections, respectively, and N = x + y + z. If Ti > 1, there is positive tracking. For systolic blood pressure (SBP) measurements (except at 6 years old) and serum cholesterol levels, all Ti were greater than 1.0 regardless of the time when tracking was commenced. Tracking indices were slightly greater in the serum cholesterol levels than in the SBP measurements. Left ventricular muscle volume indices (LVMVI) were calculated by echocardiographic measurements. In girls, the LVMVI was larger only in the above-median SBP group at the age of 12 years (P < 0.01), but the LVMVI of the higher SBP (above median) group was larger than in the lower (below median) group at every age in boys; the difference was statistically significant (P < 0.05) at 12 and 15 years of age. Left ventricular mass enlargement may occur in the prehypertensive stage in humans as well as in rats.     

Biochemical Changes in Rat Erythrocytes Caused by Ethylene Oxide Exposure

Biochemical Changes in Rat Erythrocytes Caused by Ethylene OxideExposure. MORI, K., INOUE, N., FUJISHIRO, K., KIKUCHI, M., ANDCHIBA S. (1990). Fundam. Appl. Toxicol. 15, 441–447. WhenWistar male rats were exposed to ethylene oxide (EtO) at a concentrationof about 500 ppm, 6 hr a day, 3 days a week for 2, 6, or 13weeks, hematological examination showed macrocytic, normochromicanemia with a high reticulocyte count This result raised thepossibility that the hemolytic process was responsible for theanemia. Thus, the following possible causes of hemolysis wereinvestigated with erythrocytes obtained from control and EtO-exposedrats. (1) Metabolism in erythrocytes; (a) Hexose monophosphatecycle: The activity of glucose-6-phosphate dehydrogenase, 6-phosphogluconatedehydrogenase, or glutathione perox-idase was not affected,but the activity of glutathione reductase (GR) significantlydecreased and did not recover by the addition of flavin adeninedinucleotide. Reduced glutathione content also decreased andthe glutathione stability test was positive, (b) Embden-Meyerhofpathway: Adenosine triphosphate content did not decrease, (c)Lapoport-Luebering cycle: 2,3-Diphos-phoglycerate content wasnot affected. (2) Membrane alterations: Osmotic fragility wasnot affected and the activity of acetylcholine esterase in theghost membranes of the exposed group increased. (3) Hemoglobinstability: The heat test and the isopropanol test were negative.GR has an important function in maintaining the reducing powerin erythrocytes, and the decrease in the activity caused byEtO induced an alteration of the glutathione stability. Althoughthe mechanism of EtO-induced anemia could not be clearly explained,the inhibition of GR activity might be related to the anemia.     

ATP‐Induced Dormant Pulmonary Veins Originating from the Carina Region After Circumferential Pulmonary Vein Isolation of Atrial Fibrillation

Dormant Pulmonary Veins from the Carina Region . Introduction: Elimination of transient pulmonary vein recurrences (dormant PVs) induced by an ATP injection and ablation at the PV carina region is an effective strategy for atrial fibrillation (AF) ablation. The relationship between dormant PVs and the PV carina region has not been evaluated. Methods: A total of 212 consecutive symptomatic AF patients underwent circumferential PV electrical isolation (CPVEI) with a double lasso technique. They were divided into 2 groups in a retrospective review; Group 1: those given an ATP injection during an intravenous isoproterenol infusion after the CPVEI (n = 106), and Group 2: those in which it was not given after the CPVEI (n = 106). Radiofrequency energy was applied at the earliest dormant PV activation site identified using a Lasso catheter on the CPVEI line and then PV carina region if it was ineffective. Results: After a successful PVEI, 54 patients (51%) in Group 1 had PV reconnections during an ATP injection. Acute PVEI sites were observed on the carina region within the CPVEI line in the right PVs (16%) and left PVs (10%). Dormant PVs were reisolated at the carina region in the right PVs (23%) and left PVs (26%). The distribution of the dormant PV sites, except for the RIPV, significantly differed from that of the acute PVEI sites (P < 0.05). Further, AF recurred significantly in the Group 2 patients as compared to those in Group 1 during 16 ± 6.1 months of follow‐up (P < 0.05). Conclusion: PV carina region origins may partly be responsible for an acute PVEI and potential recurrences. (J Cardiovasc Electrophysiol, Vol. 21, pp. 494‐500, May 2010)