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Biomedical subjects

E Okajima

Publications and source records attributed to E Okajima.

At least 55 records · Page 3Linked to original sources

[Long-term follow-up of female tetraplegic patients with cutaneous vesicostomy].

Tetraplegic women who underwent a cutaneous vesicostomy in our institutions were studied to evaluate long-term urinary complications and their quality of life (QOL). A total of 5 patients (C4, C5 and C6 injuries in one patient each and C7 injury in 2) were followed for 98 to 125 months (mean 107 months). Autonomic hyperreflexia disappeared after surgery in all patients. None of the patients showed deterioration of the upper urinary tract. Urinary tract infections were noted in 3 of 5 patients, but not severe. Bladder stones developed in 2 patients and a stomal stricture in 1. A questionnaire survey showed the patients to be satisfied with the operation, which had improved their QOL. These findings suggest that a cutaneous vesicostomy is an excellent surgical procedure for tetraplegic women.

Adult↗

Infrequent Ki-ras and an absence of p53 mutations in hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats.

Mutations of Ki-ras and p53 genes in hepatocellular carcinomas (HCCs) induced by the choline deficient L-amino acid defined (CDAA) diet in rats were investigated by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis followed by direct sequencing. Male Fischer 344 rats, 6 weeks old, were continuously given a CDAA diet for 70 weeks and then sacrificed. Macroscopically detectable nodules which were histologically confirmed to be well-differentiated HCCs were dissected free from the surrounding tissue and subjected to gene mutation analysis along with samples of non-tumor areas. Conformational change in the Ki-ras gene was detected in 1 out of 7 HCCs, involving a GGC to GTC transversion at codon 13. No p53 mutations were detected in 7 HCCs and also neither Ki-ras nor p53 mutations were found in non-tumor areas. The results suggest that neither Ki-ras nor p53 genes play an important role in hepatocarcinogenesis caused by long term expose to a CDAA diet in rats.

Amino Acids↗

Enhancement of N-nitrosodiethylamine-initiated hepatocarcinogenesis caused by a colchicine-induced cell cycle disturbance in partially hepatectomized rats.

The effects of a colchicine-induced M-phase block of regeneration after partial hepatectomy on early-stage liver carcinogenesis were studied in rats. When administered 1 or 3 days after N-diethylnitrosamine initiation and partial hepatectomy, colchicine increased the mitotic index of regenerating hepatocytes at days 4-6 without evidence of liver cell necrosis. When the protocol was combined with a selection procedure (E. Cayama et al., Nature (Lond.), 275: 60-62, 1978), a significant increase in the size but not number of gamma-glutamyltranspeptidase-positive foci at week 5 was observed in a colchicine dose-dependent manner. This was associated with an elevated incorporation of 5-bromo-2-deoxyuridine into the gamma-glutamyltranspeptidase-positive cells. In a longer-term experiment, the numbers, sizes, and 5-bromo-2-deoxyuridine labeling index of persistent nodules were increased significantly in colchicine-treated rats at week 9. This was associated with significant increases in the incidences and numbers of hepatocellular carcinomas at week 42. The above results raise the interesting possibility that a cell cycle disturbance in the early stage of liver carcinogenesis provides a persisting growth advantage for initiated cells, resulting in enhanced growth of foci and persistent nodules that evolve into hepatocellular carcinomas.

Animals↗

Infrequent somatic alteration of p16/MTS1 in human primary superficial bladder cancers.

Although superficial bladder cancer, usually presenting as low grade transitional cell carcinomas, are easily resected by transurethral intervention, their frequent recurrence and progression of satage or grade of the recurrent tumors in some cases is a major problem in urology. Deletion of chromosome 9, bands 9p21-22 in bladder cancers including the lowest grade and stage, suggest potential location of candidate tumor suppressor genes. Recently, p16/MTS1 was isolated from 9p21-22 as a multiple tumor suppressor gene, which regulates the cyclin dependent kinase 4 in the G1/S phase of the cell cycle. In the present study, somatic alterations of p16/MTS1 were examined concentrating on histologically defined superficial bladder carcinomas by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) technique using paraffin embedded materials. Infrequent alterations of p16/MTS1 in superficial bladder cancers, one deletion and one silent mutation in 15 cases, were detected. The results suggest that p16/MTS1 mutation is not involved in the development of superficial urinary bladder carcinomas.

Base Sequence↗

Urethral opening pressure in patients with myelodysplasia.

We evaluated 60 patients with myelodysplasia using the urethral opening pressure (UOP) which is defined as the total intravesical pressure at the moment when urine passes through the external sphincter by the Credé or the Valsalva maneuver. Twenty nine of the patients showed UOP value greater than 35 cmH2O and 31 below 35 cmH2O. In the high pressure group, patients showed a tendency to preserve sphincter activity and had mild paralysis of the lower extremities. In contrast, most of patients in the low pressure group showed an underactive sphincter and severe paralysis of the lower extremities. The incidence of deterioration of the upper urinary tract, vesicoureteral reflux (VUR) and bladder deformity were significantly high in the high pressure group than those in the low pressure group (75.9% vs 16.1%, 72.4% vs 22.6%, 82.8% vs 29.0%, respectively, P < 0.05). During the follow-up period (42 months on average), the voiding methods were changed in 15 patients from the Credé maneuver to clean intermittent catheterization, and total of 12 operations were performed (10 antiVUR operation and two with an ileocystoplasty). Finally, approximately 90% of the patients in both the high and the low pressure groups were evaluated as improved or stable in the upper urinary tract, VUR and bladder deformity after conservative or surgical managements. UOP is considered to be one of the useful parameters to select the high risk patient in the urological management of myelodysplastic patients.

Adolescent↗

Disturbance of the cell cycle with colchicine enhances the growth advantage of diethylnitrosamine-initiated hepatocytes in rats.

The effect of cell cycle disturbance due to colchicine on the induction of enzyme-altered foci during liver regeneration in rats was studied. For initiation, diethylnitrosamine (DEN) at a dose of 10 mg/kg was injected intraperitoneally and partial hepatectomy (PH) was performed 4 h thereafter. Colchicine at doses of 0, 0.1, 0.25 and 0.5 mg/kg was injected intraperitoneally 1 and 3 days after the initiation, followed by application of selection pressure consisting of 2-acetylaminofluorene (AAF) and carbon tetrachloride (CCl4) administration. As end point lesions, gamma-glutamyltransferase (GGT)-positive enzyme-altered foci were assayed at week 5. There was no significant effect of colchicine on numbers of foci. However, a significant, dose-dependent increase in the area of GGT-positive lesions in the groups treated with colchicine was observed. Bromodeoxyuridine labeling indices were higher in foci induced in colchicine-treated rats than in the untreated rats. In a separate experiment, serum glutamic pyruvic transaminase was not increased significantly after DEN and colchicine treatment, and the mitotic index at 6 days after PH was increased in the liver of colchicine-treated rats. These results suggest that the cell cycle disturbance induced by colchicine causes more pronounced selective growth of cells initiated by DEN and colchicine, and this experimental model may be useful for analyzing the mechanisms underlying that growth advantage and the effects of cell cycle abnormalities in liver carcinogenesis.

Animals↗

Shortened telomere length in hepatocellular carcinomas and corresponding background liver tissues of patients infected with hepatitis virus.

The telomere length in 20 surgically resected human hepatocellular carcinomas (HCCs) and adjacent non-cancerous livers with hepatitis virus infection were investigated. All the HCC samples examined demonstrated shorter telomere length than the corresponding non-cancerous liver tissues, the respective average values being 5.4 kbp and 8.8 kbp (P < 0.001). The shortening of telomere length was most prominent in HCCs larger than 30 mm in diameter, and in both tumors and non-cancerous livers it was more marked with hepatitis B virus as compared with hepatitis C virus infection. These results indicate that telomere shortening is associated with not only progression, but also development of HCC, and there is a possible difference in the nature of the association in patients with hepatitis viruses of B and C types.

Adult↗

Estimate criteria for diagnosis and severity in benign prostatic hyperplasia.

BACKGROUND: Standard severity criteria for benign prostatic hyperplasia (BPH) are needed to facilitate clinical and epidemiologic investigations in the common terminology. PATIENTS AND METHODS: A total of 692 BPH patients from 8 institutions were judged by specialized physicians for their overall disease severity and severity in 4 domains: symptom, function, anatomy, and quality of life (QOL). The items measuring severity in these 4 domains were the International Prostate Symptom Score (I-PSS) questionnaire, uroflowmetry, transrectal ultrasonography (TRUS), and questionnaires on bother and I-PSS QOL index, respectively. By Spearman's rank correlation and multiple regression analysis using physicians' judgement as the criterion variable (gold standard) the items and their cut-off levels were selected so that high predictivity, practicality and clinical significance were maintained, while the number of items in use was minimized. RESULTS: The item(s) and their ranges of values for each severity grade were summarized as follows; the evaluation domain (the selected item(s): range of mild, moderate, severe): symptom (I-PSS: 0-7, 8-19, 20-35), function (maximum flow rate and residual urine volume: > or = 15 mL/s and < 50 mL, > or = 5 mL/s and < 100 mL, < 5 mL/s or > or = 100 mL), anatomy (prostate volume on TRUS: < 20 mL, < 50 mL, > or = 50 mL), QOL (QOL index: 0 and 1, 2 to 4, 5 and 6). The overall severity was efficiently predicted when defined according to the combinations of severity grades of the 4 domains. These criteria predicted physicians' judgement with accuracy of about 80% for overall severity and severity of individual domains. CONCLUSION: The proposed criteria are valid, practical, and would be useful for the common scale of the BPH severity in clinical and epidemiologic studies.

Humans↗

Estimate criteria for efficacy of treatment in benign prostatic hyperplasia.

BACKGROUND: Various treatment modalities for benign prostatic hyperplasia (BPH) have emerged and are now in use or await evaluation of clinical usefulness. It is difficult, however, to compare their efficacies on a single scale, because standardized criteria for therapeutic efficacy of BPH treatments have not been established. PATIENTS AND METHODS: A total of 692 BPH patients from 8 institutions in Japan received various treatments, and were judged by specialized physicians for overall efficacy, and for efficacy in 4 domains: symptom, function, anatomy, and quality of life (QOL). Efficacy of treatment was graded as excellent, good, fair or poor, and assessed using items based on conventional clinical measurements. These items included 1) the difference (post-pretreatment value), 2) relative ratio (post/pre) and, 3) the individual values of pre- or posttreatment measurements. The cut off levels for each grade were heuristically selected by Spearman's rank correlation and multiple regression analysis so that the results accurately predicted physicians' judgement, while the feasibility was maintained. RESULTS: The results for each efficacy grade (range of excellent, range of good, range of fair, range of poor) were summarized as follows: Symptom: (post/pre treatment ratio of I-PSS) < or = 0.25, < or = 0.5, < or = 0.75, > 0.75. Function: (post-pre of Qmax) > or = 10 mL/s, > or = 5 mL/s, > or = 0.25 mL/s, < 0.25 mL/s. Anatomy: (post/pre ratio of prostate volume) < or = 0.5, < or = 0.75, < or = 0.9, > 0.9. QOL: (pre-post of QOL index) > or = 4, 3, 2 and 1, < or = 0. The overall efficacy grade was defined as the median of efficacy grades of 3 domains: symptom, function and QOL. The agreement rates between the criteria and physicians' judgement on the dichotomous efficacy (either excellent plus good, or fair plus poor) were approximately 80% in individual domains and overall estimate, and consistent among various treatments. CONCLUSION: The proposed criteria are fairly accurate, simple, and practical, and thus may be useful as a standard method for assessing the clinical efficacy of BPH treatments.

Evaluation Studies as Topic↗

[Treatment for hormone-refractory or relapsing prostatic cancer].

Androgen ablative treatments for advanced prostatic cancer have achieved great progress with new concepts of therapy in the last decade such as chemical castration with LH-RH analogue and total androgen ablation. However, in treatment for hormone-refractory or relapsing prostatic cancer it remains controversial whether cytotoxic chemotherapy is acceptable or palliative, and whether there is an alternative treatment for this incurable disease. The current status of cytotoxic chemotherapy for advanced prostatic cancer patients in Nara Medical University since 1980 is reported in this paper with the some review of recent advances in hormone-independent prostatic cancer treatment. The overall objective response rate of CDDP-based multi-drug regimens including CDDP monotherapy was 49.6% (CR 0% + PR 49.6%). Response rate of primary chemotherapy group constituted with untreated patient was 67.2%, against 23.9% in the hormone refractory or relapse group. Five-year survival rate was 61.1% in the primary chemotherapy group, 35.5% in the hormone refractory group and 40.6% in the relapse group. Basically, there was no significant difference in response rates and survival rates among the groups of CDDP monotherapy, CDDP+bleomycin+vinblastine, CDDP+cyclophosphamide+adriamycin or CDDP+etoposide. The different response rates among the regimens seemed mainly to depend on the population of refractory or relapsing cases in each group. The important problems remaining unsolved in the research of chemotherapy for prostatic cancer are that there is no effective breakthrough agent and the lack of the harmonization in response criteria. The new agents are under development based on the cellular biology of hormone-refractory prostatic cancer, and there is a bright future in the treatment of this intractable disease.

Aged↗

[Plasma allantoin in patients undergoing maintenance hemodialysis].

Recently, it has been noted that radical molecules participate in the pathogenesis of some of the complications associated with long-term dialysis therapy, such as amyloidosis. Since allantoin is produced from uric acid almost exclusively by the hydroxy radical, we investigated the plasma concentrations of allantoin in 71 patients with chronic renal failure who were on maintenance hemodialysis. Our specific objective was to investigate the relation of allantoin to the plasma concentrations of beta2-microglobulin and methylguanidine to evaluate the potential of allantoin as a significant parameter of the radical reaction. Although plasma allantoin was not detected in 15 healthy controls, plasma concentrations of allantoin increased markedly in all of the hemodialysis patients (42.6 +/- 37.7 nmol/mL) and wide variation was observed from 4.3 to 185.2 nmol/mL. In addition, we confirmed significant correlations between plasma concentrations of allantoin and beta2-microglobulin as well as serum concentrations of methylguanidine/creatinine and hyaluronic acid (r - 0.456, p < 0.0005, r = 0.313, p < 0.005, r = 0.368, p < 0.01, respectively). Although evidence for a direct link between plasma allantoin levels and amyloidosis was not obtained, the increase in the plasma concentrations of allantoin suggested its clinical significance as a parameter of the radical reaction that is thought to participate closely in the pathogenesis of dialysis-related amyloidosis. From a practical point of view, the measurement of plasma allantoin can be expected to become a significant method of measuring radical members which may be useful in the prophylaxis of some of the complications induced by free radicals.

Adolescent↗

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral↗

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral↗

[Serum and urinary pyridinium cross-links in patients with predialysis chronic renal failure].

The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were simultaneously measured in both serum and urine samples by ion-paired high-performance liquid chromatography in 27 patients with predialysis chronic renal failure. The patients consisted of 19 males and 8 females, whose creatinine clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal function on serum Pyr and the clinical significance of serum and urinary Pyr were analyzed in patients with predialysis chronic renal failure. There were significant correlations between serum Pyr and serum Cr (r = 0.76) and between Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3) was correlated with neither serum nor urinary Pyr. There was no correlation between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH, osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr, although it was statistically significant (p < 0.1). These date led to the following conclusions: (1) serum Pyr in patients with oredialysis chronic renal failure is influenced by reduced renal function and (2) urinary pyr shows a state of bone resorption when an adegvafe level of renal function is maintained. This suggests that patients with an advanced stage of renal osteodystrophy are included among cases of predialysis chronic renal failure.

Adult↗

[Serum prostate specific antigen for the early detection of prostate cancer in outpatients of internal medicine].

Screening was performed on 102 patients aged 60 years or older who visited the Outpatient Department of Internal Medicine in Tane General Hospital between June 1994 and May 1995. Of those screened, 36 patients (35.3%) had elevated prostate specific antigen (PSA) values, and 20 of them visited the Urological Department, and underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for further screening. Of the 16 patients who underwent ultrasound guided biopsies of the prostate, 7 patients were found to have prostate cancer. Therefore, the cancer detection rate was 6.9%, which was about 4 times higher than that of mass-screening examinations previously reported in the Japanese literature. These findings suggested that the screening using PSA in outpatients of Internal Medicine may be useful for the early detection of prostate cancer.

Aged↗

[The role of prostate specific antigen in diagnosis of localized adenocarcinoma of the prostate. Nara Uro-Oncology Research Group].

The number of cases of prostate carcinoma (PCA) is steadily inceasing in Japan. The clinical application of a reliable tumor marker, prostate specific antigen (PSA) for the diagnosis, as well as the increasing elderly population in Japan may account for this increase. The subjects were patients at the Nara Medical University and its affiliated hospitals; 1) 687 cases without PCA were evaluated for age-specific PSA and the incidence of abnormal PSA following urological manipulations, 2) 135 cases with histological proven BPH by transurethral resection of prostate (TUR-P) were examined for PSA density (PSAD) and positive PSA rate in BPH, 3) 135 cases receiving a needle biopsy with suspicion of PCA were examined for the efficacy of PSA and PSAD and other parameters, and 4) 459 PCA cases treated between 1988 and 1994, were examined for specific PSA and PSAD values by stage and degree of cell differentiation. The PSA assay used in this study was MARKIT-M PA (normal range < or = 3.6 ng/ml). The PSA was decreased gradually with age in non-PCA patients, and abnormal PSA was found in 5.5% of these patients following manipulations. The average PSA was 2.95 +/- 2.03 ng/ml in 130 BPH patients (mean age: 71.1 +/- 7.0 years old. and average prostate volume: 32.9 +/- 16.1 ml). And abnormal PSA level (more than 3.61 ng/ml) was found in 22.3%. The mean PSAD was 0.1.0 +/- 0.06, and PSAD was below 0.15 in 86.1% of these BPH cases. Among the 135 cases receiving a needle biopsy, 33 cases had PSA values between 3.61 and 10.0 ng/ml. Of these cases, PCA was found in 18.5% of the 27 cases with a PSAD below 1.5, and in 33.3% of the 6 cases with a PSAD over 1.5. PSA and PSAD were proportionally increased with stage, and a significant difference in the PSA value was observed between stage B1 and B2, and stage C and D (P < 0.05). However, PSA and PSAD values were not significantly correlated with the cell differentiation in PCA stage A2-C. In total, PSA was 18.1 ng/ml in well, 23.9 ng/ml in moderately and 35.9 ng/ml in poorly differentiated type PCA. The positive rate of PSA was 22.3, 65.4 and 83.5%, that of prostate acid phosphatase (PAP) was 10.0, 17.8 and 45.8%, and that of GSM was 25.0, 14.7 and 68.4%, in BPH, stage A PCA and stage BPCA, respectively. In conclusion, PSA is the most reliable tool in the diagnosis of localized PCA. However, the differential diagnosis of BPH and localized PCA is difficult when the PSA value is between 3.61 and 10.0 ng/ml, and accurate staging of localized PCA is difficult with PSA or PSAD alone. At present, it is necessary to use all possible tools for the early detection of localized PCA, and to perform the needle biopsy in all PCA-suspicious cases.

Acid Phosphatase↗

[Clinical study of testicular cancer].

Since April 1986, a prospective clinical trial for testicular cancer has been underway by our Nara Uro-Oncology Research Group. One hundred and forty-eight cases of germ cell tumor were entered into this study between April, 1986 and August, 1995. They included 99 cases (66.9%) of seminoma and 49 cases (33.1%) of non-seminomatous germ cell tumor (NSGCT). The mean age of seminoma cases (39.7 yrs) was higher than that (30.2 yrs) of NSGCT cases. One hundred and twenty-three cases were treated according to our protocol. In the treatment group, one patient with stage I seminoma died of other diseases and one patient each with stage II and stage III seminoma died of cancer. Three patients with stage III NSGCT died of cancer. The 5-year survival rate was 100% for stage I seminoma, and stage I and stage II NSGCT, 75.0% for stage II seminoma, 0% for stage III seminoma and 66.7% for stage III NSGCT. These findings suggest that new treatment modalities should be introduced into our protocol in the future.

Adolescent↗