Search PubMed⌕ Search

Biomedical subjects

A Gotoh

Publications and source records attributed to A Gotoh.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of retinoic acid and interferon-gamma on expression of the retinoic acid receptor in mouse renal cell carcinoma.

The clinical outcome of interferon-gamma treatment of metastatic renal cell carcinoma remains unsatisfactory. To overcome this, a reagent that has a different action on cancer cells is desired. One such candidate may be 13-cRA (cis retinoic acid), a vitamin A derivative known to markedly regulate the differentiation and proliferation of normal and neoplastic cells. Moreover, 13-cRA demonstrates a remarkable synergistic effect with IFN-gamma in certain types of cancer. We investigated the efficacy of concomitant administration of 13-cRA and IFN-gamma. The in vivo anti-tumor effects were evaluated in a lung metastasis model using a mouse renal cell carcinoma cell line (RenCa). The in vitro anti-tumor effects were also assessed by MTT assay. The presence of retinoic acid receptors (RAR)-alpha, -beta and -gamma was examined by PCR analysis. The influence of IFN-gamma on these retinoic acid receptors was evaluated by Northern blotting. IFN-gamma showed anti-tumor effects both in vivo and in vitro. This effect was enhanced synergistically with concomitant 13-cRA treatment. RenCa cells expressed RAR-alpha, and -gamma, but not -beta according to PCR analysis. IFN-gamma treatment increased the expression level of RAR-alpha and RAR-gamma according to Northern blot analysis. Combination therapy using IFN-gamma and 13-cRA showed synergistic anti-tumor effects, which exceeded those of each therapy alone. Moreover, IFN-gamma treatment increased RAR-alpha and RAR-gamma expression. Thus, the augmented anti-tumor effects of IFN-gamma and 13-cRA may be attributable to enhanced expression of RAR-alpha and RAR-gamma by IFN-gamma treatment.

Animals↗
PubMed2001

[Laparoscopic radical prostatectomy: initial 17 case report].

PURPOSE: We report our early experience of laparoscopic radical prostatectomy for clinically localized prostatic cancer. MATERIAL AND METHOD: Between April and December 2000, 17 patients with clinical stage T1c to T2b prostatic cancer underwent laparoscopic radical prostatectomy. The median age was 70.9 year old, the median preoperative PSA and the median Gleason score of biopsy specimens was 7.1 ng/ml, 6, respectively. We followed the operation technique from the "Montsouris technique". Briefly, we used five trocars (two 10-mm and three 5-mm trocars) and the operation was performed transperitoneally. Pelvic lymph node dissection was performed in only one patient (case 3). Urethrovesical anastomosis was performed with 6 to 9 interrupted 3-0 absorbable sutures. RESULTS: No conversion to open surgery or reoperation was required in all cases. Median operation time was 450 minutes (range 290 to 750) and median intraoperative bleeding (including urine) was 600 ml (range 100 to 3,135). Only one case (case 3) needed homologous blood transfusion. Median postoperative Foley catheterization period was 9 days (range 5 to 19). Intraoperative complications related to operation procedure were one rectal injury and three vesical injuries, which were treated by absorbable suturing laparoscopically. Major complication was one complete A-V block (case 3) who was required a transient discontinuance of the procedure. Surgical margins were negative in 13 cases. Postoperative pathological evaluation was one pT0, five pT2a, seven pT2b and four pT3a. PSA value decreased less than 0.2 ng/ml after surgery in all patients. Although six months have passed after the surgery in only 4 patients, all of them were fully continent. CONCLUSION: Although the operation time is still longer than that of conventional open procedures, intraoperative magnified vision allows a more precise and safer dissection, especially for apical dissection. We believe that operative time will decrease with more experience. These results show that laparoscopic radical prostatectomy can be an acceptable treatment option for localized prostatic cancer.

Aged↗
PubMed2001

Long-term results of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with clinically localized prostate cancer: biochemical and pathological effects.

The objective of this study was to evaluate the long-term biochemical and pathological effects induced by neoadjuvant hormonal therapy (NHT) in patients with clinically localized disease. Between March 1993 and May 1997, 24 patients with clinically localized prostate cancer received NHT for 3 to 11 months (median: 5 months) using luteinizing hormone-releasing hormone analogue prior to radical prostatectomy and pelvic lymphadenectomy. The clinical stage was T1 in 1 patient, T2 in 17 and T3 in 6, the pretreatment serum prostate-specific antigen (PSA) value was < or = 10 ng/ml in 5 patients, 10 to 20 ng/ml in 4 and > 20 ng/ml in 15 (mean: 34.7 micrograms/l), and the Gleason score was < or = 4 in 9 patients, 5 to 7 in 11 and > 8 in 3. The mean prostate specific antigen (PSA) value 3 months after NHT had reduced below 2 ng/ml in 18 of the 24 patients (67%), and finally decreased by an average of 95% (i.e., 1.9 ng/ml) prior to surgery. The pathological stage was pT0 in 2 patients, pT2 in 10 and pT3 in 12. The incidence of organ-confined disease (OCD) was significantly higher in patients with clinical stage T1 or T2a than with T2b or T3, with pretreatment PSA values < or = 10 ng/ml than with PSA values > 10 ng/ml, and with PSA values < or = 2 than with PSA values > 2 at 3 months after NHT; in contrast, the Gleason score had no significant impact on the rate of OCD. After a median follow-up of 49 months (range 34 to 85 months), 6 patients (25%) had a recurrence evidenced by rising PSA, and the 3-year recurrence-free survival rate was 79%. These results suggest that NHT appears not to be of significant additional benefit to patients who have a higher clinical T stage, higher pretreatment PSA values and/or in patients whose PSA values do not normalize early in the treatment process.

Aged↗
PubMed2001

[Prospects for molecular research in urological oncology: gene therapy].

The recent great advances in genetic engineering are now making possible the identification and isolation of the trigger genes of many hereditary illnesses, and the clarification of the relevant molecular mechanisms. The idea that if the genetic abnormalities responsible for illness could be established at a DNA level, treatment at the genetic level repairing damaged genes or supplying absent ones would also be possible was the incentive for the recent boom in gene therapy. Clinical research into gene therapy began in 1990 and currently over 3,000 patient cases are being studied. Some 70% of these are cancer patients. This is not simply because such patients are relatively numerous, but is also a sign of the wish, held earnestly by many researchers and clinicians as well as cancer patients and their families, to at last overcome this intractable disease. Gene therapy, so far conducted mainly in the United States, has hitherto not lived up to initial expectations in its concrete results. The reason for this results mainly in technical factors, such as the rate of success in implanting genes into target cells, the rate of successful expression of the implanted genes, and the successful achievement of specific expression at the target site. Gene therapy in the form of clinical research into renal cancer and lung cancer is now under way in Japan. It is too early at this stage to evaluate this work, but the present paper takes this opportunity to give an outline of gene therapy, and to examine its current state, future prospects and problem areas with particular reference to cancer.

Bone Neoplasms↗
PubMed2000

Long-term assessment of serum vitamin B(12) concentrations in patients with various types of orthotopic intestinal neobladder.

OBJECTIVES: Vitamin B(12) deficiency is an important long-term problem after urinary diversion using an intestinal segment. In this study, we examined serum vitamin B(12) concentrations in patients with neobladders constructed from various intestinal segments to determine the anatomic factors important for avoiding vitamin B(12) deficiency. METHODS: Twenty-two patients (19 men and 3 women) had an ileal neobladder (modified Studer type); 9 men had an ascending colonic neobladder (Goldwasser type); 30 patients (24 men and 6 women) had a sigmoid neobladder (modified Reddy type); and 18 (15 men and 3 women) had an ileocolic neobladder (Mainz type). The postoperative follow-up ranged from 3 months to 11 years (mean +/- SD, 3.4 +/- 2.8 years). The serum vitamin B(12) concentration was determined at several points after surgery. RESULTS: No patient with a neobladder fashioned from ascending or sigmoid colon developed a low vitamin B(12) concentration. Of the 18 patients with an ileocolic neobladder, 3 (16.6%) developed decreased serum vitamin B(12) concentrations after 5 to 6 years. Of the 22 patients with an ileal neobladder, 3 (13.6%) developed a low serum concentration of vitamin B(12) between 9 months and 3 years after surgery. No patient developed megaloblastic anemia or neurologic symptoms. CONCLUSIONS: Preservation of the terminal 15 cm of ileum is not sufficient to ensure adequate vitamin B(12) absorption, and thus, preserving the ileal length is important. Use of colonic segments to construct neobladders appears to be preferable to ileal segments to preserve vitamin B(12) absorption.

Aged↗
PubMed2000

Health-related quality of life with orthotopic neobladder versus ileal conduit according to the SF-36 survey.

OBJECTIVES: To compare health-related quality of life (HRQOL) in patients with a neobladder and in patients with an ileal conduit. METHODS: HRQOL was assessed using the SF-36 survey, supplemented with a questionnaire concerning micturition status. RESULTS: Patients (n = 36) with a neobladder were significantly younger at time of surgery and time of survey than patients with an ileal conduit (n = 20). Mean (+/- SD) follow-up periods for patients with a neobladder and with an ileal conduit were 31.3 +/- 33.1 and 44.8 +/- 30.7 months, respectively. No significant difference was apparent in any scale score between neobladder and ileal conduit groups. Role-physical functioning (RP) and role-emotional functioning (RE) scale scores in both neobladder and ileal conduit patients appeared to be below the general U.S. population norm. Patients with neobladder 65 years old or older (n = 17) showed significantly lower RP and RE scores than those younger than 65 years (n = 19; P <0.05). Duration of follow-up was not related to scale scores. Continence status did not measurably affect HRQOL. CONCLUSIONS: All scales concerning HRQOL except RP and RE were favorable with both neobladder and ileal conduit, and no significant differences were observed between these two types of urinary tract reconstruction. Generally, patients with a neobladder or an ileal conduit were satisfied with their overall quality of life and health.

Aged↗
PubMed2000

Tissue-specific promoters in gene therapy for the treatment of prostate cancer.

Delivery of therapeutic toxic genes to and their expression in tumor cells through the use of tissue-specific promoters could decrease their toxic effect on neighboring normal cells when virus-mediated gene delivery results in their infection. We have demonstrated the utility of two prostate cancer-specific promoters, long PSA and osteocalcin, for tissue-specific toxic gene therapy for prostate cancer. The two promoters were highly active in both androgen-dependent and androgen-independent prostate cancer cells. We also introduce the Phase I trial of osteocalcin promoter-based toxic gene therapy for bone metastases of prostate cancer, which is in progress at the University of Virginia.

Acyclovir↗
PubMed2000

Tumor necrosis factor-alpha represses androgen sensitivity in the LNCaP prostate cancer cell line.

PURPOSE: Prostate tumor progression is characterized by development of androgen independence and a heterogeneous distribution of the androgen receptor (AR). Tumor necrosis factor alpha (TNFalpha) has been demonstrated to contribute to the progression of several cancers and thus may play a role in prostate cancer progression. Accordingly, we examined if prostate cancers express TNFalpha and the effect of TNFalpha on androgen sensitivity and AR expression in LNCaP prostate cancer cells. MATERIALS AND METHODS: Immunohistochemical analysis of prostate tissues, ELISA, and northern blotting of LNCaP cell lines were carried out for detection of tumor necrosis factor-alpha (TNFalpha). To see the effect of TNFalpha on androgen receptor (AR), western blotting and northern blotting were performed after extraction of total protein and total RNA from LNCaP cells. Regulation of androgen-sensitivity by TNFalpha was investigated with cell proliferation assay and luciferase assay using PSA promoter after transfection of LNCaP cells. RESULTS: Immunohistochemical analysis demonstrated that TNFalpha protein was strongly expressed in epithelial cells of prostate cancer tissue but not in normal prostatic tissue. Basal level of TNFalpha in cell culture medium from LNCaP cells was very low. However, 12-O-tetradecanoylphorbol 13-acetate (TPA) induced TNFalpha secretion into medium up to 1600 pg/ml/day. Furthermore, 24 hr. post-TPA treatment TNFalpha mRNA levels were increased 15-fold compared to pre-treatment levels. TNFalpha (0 to 30 ng./ml. for 4 days) repressed AR protein and mRNA levels in a dose-dependent fashion in LNCaP cells. Pre-treatment of cells with actinomycin D treatment revealed that repression of mRNA levels was exerted at the post-transcriptional level. TNFalpha inhibited the ability of 10-9 M dihydrotestosterone (DHT) to induce LNCaP cell proliferation and activation of the prostate specific antigen (PSA) gene promoter. This inhibition was partially reversed by overexpression of transgenic androgen receptor. CONCLUSIONS: TNFalpha is present and inducible in prostate cancer cells and short-term TNFalpha diminishes androgen-sensitivity in LNCaP cells through down-regulation of AR protein and mRNA levels. These results suggest that TNFalpha may play a role in the initiation of an androgen-independent state in prostate cancer through its ability to inhibit AR sensitivity in prostate cancer.

Antibiotics, Antineoplastic↗
PubMed2000

Outbreak of cryptosporidiosis after contamination of the public water supply in Saitama Prefecture, Japan, in 1996.

An outbreak of cryptosporidiosis occurred in Ogose Town, Saitama Prefecture. Japan, in June 1996. Of 12,345 respondents to a questionnaire sent to households in the town (population; 13,809), 8,812 (71.4%) reported an acute gastrointestinal illness some time between May and July. In addition, 274 traceable visitors at local inns, golf courses, and the like during this period and 54 employees from out of town were infected. Cases of cryptosporidiosis were estimated to 9,140. Of these, 2,856 subjects were treated at outpatient clinics and 24 subjects were hospitalized (some subjects counted twice). No deaths were attributed to the outbreak. Among the visitors to Ogose who were traced, 7 persons who stayed only one day during the outbreak and drank half a glass to 2 glasses (100 to 360 ml) of tap water had cryptosporidiosis confirmed by laboratory tests. The median incubation period for the 14 persons for whom this calculation was possible was 6.4 days (range, 5 to 8 days). Of 469 pupils reporting details of their fever and diarrhea, abdominal cramps, or these combined signs and symptoms, the median maximum body temperature was 37.8 degrees C (range, 36.7 to 40.3 degrees C). The duration of illness, reported by 608 of the pupils, was 5.2 days (range, 1 to 15 days), and that reported by 187 employees was 4.8 days (range, 1 to 18 days). The longest known time for discharge of oocysts after onset was 44 days. Blood was not found in the 609 stool specimens examined. The outbreak was caused by contamination of the town's potable water by Cryptosporidium parvum oocysts. The town's water treatment plant treated river water by coagulation, sedimentation, sand filtration, and chlorination. Contamination arose because of various natural and artificial factors: one was that the monthly precipitation in May was much lower than average, causing the river water level to drop. Another factor was heavy rainfall one night in May that increased water turbidity. The amounts of the coagulant added seemed to be insufficient. There are two inns, three public lavatories, and two small-scale wastewater treatment plants upstream 400 m and 1,200 m of the intake point of the town's water treatment plant. However, there are no farms with livestock in the area. We suggest that the location of the water treatment facilities was inappropriate, and that oocysts had circulated from the potable water to humans to sewage to the river and back to the potable water.

Adolescent↗
PubMed2000

In vitro activities of rabeprazole, a novel proton pump inhibitor, and its thioether derivative alone and in combination with other antimicrobials against recent clinical isolates of Helicobacter pylori.

The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinical Helicobacter pylori strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole. Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined. Moreover, no apparent antagonistic effect appeared among all of the strains tested.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Changes in calcium metabolism and bone demineralization after orthotopic intestinal neobladder creation.

PURPOSE: We evaluated calcium metabolism and bone demineralization by measuring specific markers for bone reabsorption and bone mineral density in patients with an intestinal neobladder. MATERIALS AND METHODS: We studied 33 men 55 to 72 years old who underwent creation of an orthotopic sigmoid (23), ileocolic (8) or ascending colon (2) neobladder after cystectomy. Mean followup plus or minus standard deviation (SD) was 28.4+/-30.1 months (range 4 to 114). Serum electrolytes and arterial blood gases were measured. As markers of bone absorption we assayed urinary pyridinoline, deoxypyridinoline and N-terminal pyridinoline cross-linked telopeptides, and serum pyridinoline cross-linked C-terminal telopeptide of type I collagen. Bone mineral density of the spine and femur was determined by dual x-ray absorptiometry. RESULTS: Mean blood pH plus or minus SD was 7.38+/-0.04 (range 7.29 to 7.43). Mean plasma bicarbonate was 22.9+/-3.4 mmol./l. and mean base excess was -1.63+/-3.61 mmol./l. Serum sodium, potassium, calcium, alkaline phosphatase and phosphate were normal in most patients. Mean serum chloride was 108.0+/-3.5 mEq./l., and was elevated in 9 of the 33 patients (27.3%). Serum intact parathyroid hormone was normal in all patients, osteocalcin was increased in 2 and 1alpha, 25-dihydroxyvitamin D3 was decreased in 2. Pyridinoline cross-linked C-terminal telopeptide of type I collagen was higher in 19 of 33 cases (57.6%) and N-terminal pyridinoline cross-linked telopeptides were elevated in 6 (18.2%). Pyridinoline and deoxypyridinoline were higher than normal in 19 (57.6%) and 7 (21.2%) patients, respectively. C-terminal telopeptide of type I collagen and deoxypyridinoline significantly correlated with serum pH (p = 0.017 and 0.0418, respectively). Z score for the bone mineral density of L2 to L4, the femoral neck and Ward's triangle was -0.350+/-1.031, -0.82+/-0.99 and -0.94+/-1.01, respectively. CONCLUSIONS: In patients with a neobladder of intestinal segments metabolic acidosis results in increased bone absorption and decreased bone mass. Thus, attention should be given to bone metabolism in patients with even mild acidosis after orthotopic neobladder creation.

Aged↗
PubMed2000

Sigmoid neobladder in women after radical cystectomy.

PURPOSE: Neobladder reconstruction using an intestinal segment is the common procedure of choice in men after cystectomy. Recently this procedure has been extended to women. We present our surgical and functional experience with the sigmoid neobladder in women. MATERIALS AND METHODS: A total of 11 women 49 to 74 years old (mean age plus or minus standard deviation 60 +/- 8.5) with transitional cell carcinoma of the bladder underwent lower urinary tract reconstruction with a modified sigmoid neobladder after nerve and urethral support sparing cystectomy. After at least 3 months voiding pattern and continence status were evaluated. Pressure flow studies and uroflowmetry were performed, the urethral pressure profile and neocystourethral angle were measured, and blood chemistry was analyzed. RESULTS: After at least 3 months complete daytime continence was achieved in 2 patients, while 8 had mild stress incontinence. At night 8 of the 11 women (72.7%) were continent with or without voiding at regular intervals. All except 1 patient voided to completion. Of the 2 patients with complete continence 1 needed clean intermittent catheterization 4 months postoperatively. Mean maximal urinary flow was 19.9 +/- 10.5 ml. per second. Excluding the woman who required catheterization mean residual urine volume was 15 +/- 13.7 ml. Postoperatively maximal urethral pressure was slightly lower and functional urethral length was about 10 mm. shorter than preoperatively. The mean neocystourethral angle was 131.9 +/- 21.7 degrees. Mean pH, bicarbonate and base excess were 7.38 +/- 0.03, 23. 48 +/- 2.34 mmol./l. and -0.92 +/- 2.50, respectively. CONCLUSIONS: After nerve and urethral support sparing cystectomy a modified sigmoid neobladder may be constructed in women to obtain satisfactory continence and voiding results.

Aged↗
PubMed2000

Diagnostic value of MRI for the female urethral diverticulum.

A woman, who discharged pus at the time of intercourse, was diagnosed to have a urethral diverticulum by combination of urethroscope and MRI. MRI provided clear view of the diverticulum in terms of the relationship with the surrounding organs.

Adult↗
PubMed1999

Modulation of integrin function in hematopoietic progenitor cells by CD43 engagement: possible involvement of protein tyrosine kinase and phospholipase C-gamma.

Attachment of cells to extracellular matrix components is critical for the regulation of hematopoiesis. CD43 is a mucin-like transmembrane sialoglycoprotein expressed on the surface of almost all hematopoietic cells. A highly extended structure of extracellular mucin with negative charge may function as a repulsive barrier to hematopoietic cells. However, some investigators have shown that CD43 has proadhesive properties, and engagement of CD43 has been reported to upregulate integrin-mediated cell adhesion in T cells. We found that cross-linking of CD43 with monoclonal antibodies (MoAbs) enhanced integrin alpha4beta1 (very late antigen [VLA]-4) and alpha5 beta1 (VLA-5)-dependent adhesion of human cord blood CD34(+) cells to fibronectin. CD34(+) CD38(hi), but not CD34(+)CD38(-/low) cells responded significantly to the stimulus, suggesting that committed, but not stem and more immature progenitors are sensitive to CD43-mediated activation of integrin. To elucidate the molecular mechanism leading to integrin activation, we used the growth factor-dependent cell line MO7e. Cross-linking of CD43 induced tyrosine phosphorylation of several intracellular molecules including the protein tyrosine kinase Syk, the proto-oncogene product Cbl, and phospholipase C (PLC)-gamma2 in MO7e cells. Moreover, protein tyrosine kinase inhibitor herbimycin A and PLC inhibitor U73122 both blocked CD43-induced enhancement of adhesion to fibronectin. These results indicate that signals mediated through CD43 may increase integrin affinity to fibronectin via a pathway dependent on protein tyrosine kinase and PLC-gamma activation in hematopoietic progenitors.

Antibodies, Monoclonal↗
PubMed1999

SDF-1 suppresses cytokine-induced adhesion of human haemopoietic progenitor cells to immobilized fibronectin.

The process of haemopoietic cell homing to the microenvironment includes migration and adhesion. SDF-1 is a C-X-C chemokine that acts as a chemoattractant for haemopoietic progenitors. Adhesion of haemopoietic progenitors to immobilized fibronectin is up-regulated by stimulation with cytokines. We assessed the effects of SDF-1 on cytokine-induced adhesion of progenitor cells to fibronectin. In factor-dependent human MO7e cells and primary CD34+ cord blood cells, treatment with SDF-1 dose-dependently suppressed cytokine-induced adhesion. Pretreatment with pertussis toxin reversed adhesion-inhibition, suggesting that activation of G-coupled proteins are involved in the intracellular signalling of this process. These data suggest that SDF-1 not only acts as a chemoattractant but also participates in modulating adhesiveness of haemopoietic progenitors to extracellular matrix components.

Cell Adhesion↗
PubMed1999

Outcome of precise vesicourethral anastomosis following retropubic radical prostatectomy using a Foley catheter.

PURPOSE: In order to evaluate precise anastomosis using a Foley catheter, complications following radical retropubic prostatectomy were examined. METHODS: Twenty-one patients underwent radical retropubic prostatectomy. Precise vesicourethral anastomosis was performed, visualizing the urethral stump by raising up the urogenital diaphragm using a Foley catheter. Complications, such as prolonged urinary extravasation and temporary urinary retention, were checked when the catheter was removed. Incontinence was evaluated both within 6 weeks and more than 6 weeks after operation. Anastomotic and urethral strictures were also checked during follow up. RESULTS: The follow-up period ranged from 4 to 47 months (mean (+/- SD) 22.0 +/- 12.1 months). Eighteen of 21 patients (85.7%) achieved continence after the operation. However, two patients still had stress incontinence and one patient had mild incontinence. Neither prolonged urinary extravasation nor temporally urinary retention were observed. Anastomotic and urethral stricture were not experienced during follow up. CONCLUSIONS: Precise anastomosis using a Foley catheter is technically easy and useful, even for relatively inexperienced urologists, to perform. Patients can often achieve continence following this procedure.

Adult↗
PubMed1999

Pharmacokinetics of natural human IFN-alpha in hemodialysis patients.

A pharmacokinetic study of natural human interferon-alpha (IFN-alpha) was conducted in hemodialysis patients. Natural human IFN-alpha was intramuscularly (i.m.) administered to 8 hemodialysis patients at a single dose of 5 million IU and to 7 patients undergoing hemodialysis at the same dose once daily for 5 successive days. The serum antiviral activity was determined by a cytopathic effect bioassay. In the single dose study, the serum antiviral activity reached a maximum (Cmax) of 56.4 +/- 33.3 IU/ml at 8.3 +/- 2.7 h after dosing, and the area under the serum concentration-time curve (AUC0-24h) was 957.2 +/- 601.8 IU h/ml. The Cmax and AUC0-24h values at day 5 following the repeated dosing were both 2.6-fold higher than those of day 1, and the serum antiviral activity reached a steady state within 3 days after initiation of repeated administration. The serum antiviral activity in hemodialysis patients showed a tendency to increase compared with that in the subjects with normal renal function, but the magnitude of the differences was not great. In one nonhemodialysis patient with poor renal function (creatinine clearance < 30 ml/min), no increases in serum antiviral activity owing to repeated dosing were observed. The main adverse events seen were fever (4 of 13, 30.8%), leukopenia (3 of 13, 23.1%), and fatigue (2 of 13, 15.4%). These results suggest that dosage modifications of natural human IFN-alpha are unnecessary for patients with low renal function, even those undergoing hemodialysis.

Aged↗