[On the regional characteristics of total fertility rates: the entropy model approach].
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Biomedical subjects
Publications and source records attributed to H Uehara.
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In this article, we first present our clinical data on PDT for the treatment of gastric cancer and make a comparison between a continuous wave laser and a pulsed laser. The reasons for PDT failure in certain cases are also discussed. In the fifteen years from 1981 to 1995, we have treated a total of 76 gastric cancer lesions (73 cases), which was consist of 69 early gastric cancer lesions (66 cases) and seven advanced gastric cancer lesions (seven cases) by PDT. From 1981 to 1990, we used an argon dye laser (ADL, Models 171-08 and 375-03, Spectra-Physics, Mountain View, Calif., US) as an excitation light source for PDT with HpD (Photofrin I), DHE (Photofrin II) or PHE (freeze-dried Photofrin II). From analysis of the results in terms of the depth of cancer invasion in these 44 lesions (41 cases), the rate of cure for mucosal carcinomas was 57% (13/23), that of submucosal carcinomas was 53% (10/19), and that of carcinomas invading more than the muscularis propria was 0% (0/2). These data can be interpreted to indicate that the ADL laser beam could not penetrate and supply sufficient energy to activate HpD not only in the submoucosal layer but also in the mucosal layer. In 1990, therefore, we investigated an excimer dye laser (EDL, Hamamatsu Photonics, Hamamatsu, Japan), because its pulsed beam with extremely high peak power was expected to be more efficient at exciting HpD than continuous wave lasers such as ADL and high frequency pulsed lasers such as cooper vapor dye laser (Cu VDL). From 1990 to 1995, twenty-seven early gastric cancer lesions (27 cases) and five advanced gastric cancer lesions (five cases) were treated by PDT with EDL and PHE. Of these 32 lesions, the rate of cure for mucosal carcinomas was 100% (15/15), that of submucosal carcinomas was 75% (9/12), and that of carcinomas invading more than the muscularis propria was 20% (1/5). For the purpose of determining how much energy was required for a complete cure in early gastric cancer, and to compare the efficacy of ADL and EDL, the relation between the response (cure or no cure) and irradiated energy intensity (dose: J/cm 2) was evaluated by the depth of cancer invasion and kind of laser used in PDT. A smaller EDL dose was more effective than ADL in terms of photodynamic action.
Parathyroidectomy (PTX) is one of the treatments of choice for secondary hyperparathyroidism in chronic dialysis patients. Due to the large increase in long-term dialysis patients, hyperparathyroidism is becoming a common clinical problem. Several studies on PTX have reported various surgical procedures, but limited information is available on the incidence and risk factors of the surgery. The Okinawa Dialysis Study (OKIDS) registry is a community-based dialysis registry. It covers the entire area of Okinawa from when the use of chronic dialysis began in 1971. By the end of 1990, a total of 1,986 chronic dialysis patients were registered and 128 of these had undergone PTX by the end of 1993. The cumulative incidence of PTX was 4.3 in DM and 15.2 in non-DM per 1,000 patient-years. About half of the PTX patients underwent the surgery within 10 years of dialysis. By logistic analysis, the risk of PTX was seen to increase significantly with the duration of dialysis, P < 0.0001. Other clinical variables such as sex, age at the start of dialysis and the presence of diabetes mellitus were not significant predictors of PTX. The probability of PTX increased linearly with the duration of dialysis (r = 0.83, p < 0.0001). After the introduction of active vitamin D in 1981, the probability of PTX was significantly decreased (p < 0.05) compared to the pre-vitamin D period ('71-'80). With prolongation of the duration of dialysis, the risk of PTX increased steadily and was estimated to be 10 percent in 10 years and 20 percent in 20 years. Other uremic factors determining a pathological transformation of parathyroid tissue from reactive to autonomous growth remained to be investigated.
OBJECTIVES: Recently, it was reported that detection of K-ras point mutation at codon 12 in pancreatic juice is an objective method for the diagnosis of pancreatic cancer, but a few reports have suggested that this might represent an early event in pancreatic oncogenesis. In the present study we examined, in various patients, the occurrence of K-ras codon 12 point mutation in pancreatic juice and compared it with pancreatic juice cytology, which is also a reliable diagnostic method. METHODS: Pancreatic juice was obtained endoscopically from patients with various pancreatic disorders and those without definite diseases, and was examined cytologically and for the occurrence of K-ras codon 12 point mutation. The K-ras gene was amplified by polymerase chain reaction (PCR) and the mutation at codon 12 (GGT-->GAT) was examined by slot blot hybridization analysis. RESULTS: K-ras point mutation at codon 12 was detected in seven of 14 (50%) pancreatic cancers, in four of 10 (40%) mucin-producing tumors, in four of 13 (31%) chronic pancreatitis, and in two of 10 (20%) pancreas without definite disorders. K-ras point mutation was detected in nine of 18 (50%) pancreatic juice samples containing cancer cells, in eight of 18 (44%) pancreatic juice samples containing atypical cells, but in none of such samples containing only normal cells. CONCLUSION: Cancer cells were detected from pancreatic cancer exclusively, but K-ras point mutation at codon 12 was detected in pancreatic juice, not only from pancreatic cancer, but also from other diseases.
Two-dimensional echocardiography was used for diagnosing coronary vasospasm during the cold pressor stress test immediately after hyperventilation in five patients with suspected vasospastic angina. The test consisted of hyperventilation for 6 min and cold water pressor for 2 min under continuous electrocardiographic and echocardiographic monitoring. Coronary angiography with intracoronary injection of acetylcholine was performed in all patients within 1 month after the stress test. During the stress test, new asynergies of both the anterior and inferior walls were seen in three of the five patients, and new asynergy of the anterior wall in the other two patients. All acetylcholine induced coronary artery spasms occurred at the same locations as the new asynergies provoked by the stress test. In three patients, wall motion abnormality occurred earlier than ST segment elevation, and the other two patients had no ST changes. Chest pain was induced in three patients and delayed in comparison to electrocardiographic and echocardiographic changes. Echocardiographic monitoring during the stress test could detect spasms unaccompanied by either ST segment changes or chest pain, and could detect multivessel coronary spasms. Hyperventilation and cold pressor stress echocardiography may be used for the diagnosis of vasospastic angina.
In the treatment of adenocarcinoma of the pancreas, surgical resection is the only curative strategy. However, the long-term survival rate after pancreatectomy remains poor, and most patients died of loco-regional and/or hepatic recurrence. Thus, we should perform effective adjuvant therapies in combination with surgery, in order to completely prevent these two types of cancer relapse. The present article is designed to introduce the recent reports on the adjuvant chemo-and/or radio-therapies for this cancer. As for loco-regional control, extended pancreatectomy plus chemoradiation seems to be most promising, and preoperative chemoradiation will be more popular in the near future. In order to decrease hepatic metastasis, our "2-channel chemotherapy", a continuous infusion of 5-FU via both hepatic artery and portal vein, is very promising. If postoperative survival is improved by combining these two types of regional therapy, the role of pancreatectomy will be enlarged and more widely understood in the near future.
The relative effect of renal transplantation on survival was examined in chronic dialysis patients in Okinawa, Japan. Of 3,035 patients (1,722 men and 1,313 women) who were registered by the end of 1994 and followed up until April 1, 1995, 141 (91 men and 50 women) had undergone a renal transplantation during the follow-up period. The type of donor was a cadaver in 38 (26.9%) and a living relative in 103 (73.1%). At the end of the follow-up period, 12 (8.5%) of the patients with a renal transplant had died, 35 (24.8%) had returned to dialysis treatment, and 94 (66.7%) were alive with a functioning graft. In the patients who did not receive a transplant, 1,134 (39.2%) had died and 1,760 (60.8%) were alive and on dialysis. Cox proportional hazard analysis was performed with adjustment for sex, age at first dialysis, presence of diabetes mellitus, year of first dialysis, and predialysis co-morbid conditions. The hazard ratio (95% confidence interval) in the group with a transplant was 0.33 (0.18 to 0.59) when the hazard ratio of the group without a transplant was taken as 1.00. The patient survival rate was better in the former group. Our data provide fundamental evidence supporting the effectiveness of renal replacement as treatment. Whether the life-saving merit of renal transplantation is substantial enough to actively encourage donation remains to be clarified.
Sparganosis mansoni rarely occurs in the inguinal and perineal regions in Japan. A case of Sparganosis mansoni with a painless mass in the left inguinal region is presented. A 67-year-old male visited our hospital with a complaint of a painless mass in the left inguinal region in May, 1995, and another mass appeared in the scrotum two days after the first visit. Ultrasonography revealed a solid subcutaneous mass 2 cm in diameter. These masses were surgically excised by an inguinal approach and a parasite, 10 cm in length, was found in the mass. The parasite was diagnosed histologically as Sparganosis mansoni, which is a larva of the genus Diphyllobothrium.
Imaging the expression of successful gene transduction has been demonstrated in vivo for the first time by using an appropriate combination of "marker gene" and "marker substrate" in an experimental animal model. The herpes simplex virus 1 thymidine kinase (HSV1-tk) gene was selected as an example of a marker gene, and the recombinant STK retrovirus containing HSV1-tk was used to transduce RG2 glioma cells in vitro and in vivo. RG2TK+ cell lines expressing the HSV1-tk gene and three potential marker substrates for the HSV1-TK enzyme were evaluated. Radiolabeled 5-iodo-2'-fluoro-2'deoxy-1-beta-D-arabinofuranosyluracil (FIAU) was shown to be a substantially better marker substrate for the HSV1-TK enzyme than 5-iodo-2'-deoxyuridine or ganciclovir. The magnitude of FIAU accumulation in different RG2TK+ clones corresponded to their sensitivity to ganciclovir and to the level of HSV1-tk mRNA expression. Imaging the expression of HSV1-tk in transduced RG2 tumor cells was demonstrated in animals using quantitative autoradiography; 2-[14C]FIAU accumulation was shown to be high in RG2TK+ brain tumors growing in one hemisphere and very low in nontransduced RG2 tumors in the contralateral hemisphere. Transduction of RG2 tumor cells with the HSV-tk gene in vivo resulted in tumors which accumulated FIAU to high levels and produced clearly defined images. Given the level of FIAU accumulation in the transduced tumors, it is likely that a clinically applicable method for imaging HSV1-tk gene expression can be implemented using existing clinical imaging techniques.
The effects of concomitant administration of bombesin and of the diuretic drug amiloride on the development of large and small intestinal tumors induced by azoxymethane (AOM), the incidence of their metastasis to the peritoneum and the labeling index of intestinal adenocarcinomas were investigated in inbred Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of AOM for 10 weeks and s.c. injections of bombesin and/or a higher or lower dose of amiloride hydrochloride (amiloride) every other day until the end of the experiment in week 45. Administration of bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal adenocarcinomas. Although administration of both doses of amiloride with bombesin had little or no influence on the enhancement of intestinal tumorigenesis by bombesin, the location, histological type, depth of involvement or labeling index of intestinal adenocarcinomas, a higher dose of amiloride significantly reduced the incidence of cancer metastasis to the peritoneum. Our findings indicate that amiloride possesses an anti-metastatic activity.
The effects of prolonged administration of neuropeptide substance P (SP) on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labeling index of gastric mucosa were investigated in Wistar rats. Rats received subcutaneous injections of 12 micrograms/kg body weight of SP every other day after 25 weeks of oral treatment with MNNG. Long-term administration of SP significantly increased the incidence of gastric cancers in week 52. However, it did not affect the histological type and depth of involvement of gastric cancers. SP also caused a significant increase in the labeling index of the antral and fundic epithelial cells in week 52. These findings indicate that SP promotes gastric carcinogenesis and suggest that this effect may be related to its stimulation of antral epithelial cell proliferation.
BACKGROUND: The early diagnosis of pancreatic carcinoma through the use of traditional radiographic or ultrasonographic methods is extremely difficult. METHODS: To detect an early and potentially curable cancer of the pancreas, endoscopic retrograde pancreatography (ERP) and aspiration cytology of pure pancreatic juice were performed in 295 consecutive patients who had symptoms or findings that suggested pancreatic disease but in whom there was neither a pancreatic mass nor ductal stenosis. RESULTS: Positive cytologic results were obtained in 12 patients (4%). With the aid of intraoperative cytodiagnosis, all 12 early neoplasms of the pancreas were successfully resected. Of these 12 resected specimens, 4 were adenocarcinoma with minimal invasion, 3 were in situ adenocarcinoma and 5 were marked atypia. All 12 patients were alive with no evidence of recurrence for an average of 32 months after surgery. The 283 patients who had negative ERP-cytology results were observed, but no further cases of pancreatic cancer were found. CONCLUSIONS: Because ERP-cytology is simple to perform, safe, and reliable, it is useful in the diagnosis of patients who have early neoplasm of the pancreas.
The effects of peptide histidine isoleucine (PHI) on the incidence and histology of colon tumors induced by azoxymethane (AOM), and on the labeling index of colon mucosa were investigated in Wistar rats. Rats received weekly s.c. injections of 7.4 mg/kg body weight of AOM for 10 weeks, and of 1.0 or 4.0 nmol/kg body weight of PHI until the end of the experiment in week 35. Administration of PHI at the higher, but not the lower dosage, significantly increased the incidence of colon tumors. PHI had no influence on the histology of colon tumors or adenocarcinomas. It also caused significant increase in the labeling index of colon epithelial cells. These findings indicate that PHI enhances colon carcinogenesis, and that its effect may be related to increasing proliferation of colon epithelial cells.
The effects of combined administration of vasoactive intestinal peptide (VIP) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on development of colon tumors induced by azoxymethane (AOM), on ODC activity of the colon wall, and on the labelling index of colon epithelial cells were investigated in inbred Wistar rats. Rats received weekly subcutaneous injections of AOM for 10 weeks and subcutaneous injections of VIP every other day and drinking water containing DAP (2.5 milligrams) ad libitum until the end of the experiment at week 45. Administration of VIP significantly increased the incidence of colon tumors at week 45. It also resulted in significant increases in colon ODC activity and in the labelling index during administration of AOM, but not after its cessation. Administration of both DAP and VIP significantly reduced the enhanced colon carcinogenesis by VIP. The DAP significantly attenuated the VIP enhancement of colon ODC activity and of the labelling index during AOM administration. These findings indicate that ODC inhibition attenuated enhancement of colon carcinogenesis, and suggest that enhancement of colon carcinogenesis by VIP may be mediated through its polyamine biosynthesis.
The effects of the neuropeptide galanin on the development of colon tumors induced by azoxymethane (AOM) and on the labeling index of colon epithelial cells were investigated in Wistar rats. Treatment with galanin significantly decreased the incidence of colon tumors at week 45. Galanin did not influence the histological appearance of the colon tumors, but it slightly increased the frequency of sub-mucosal adenocarcinomas. Furthermore, it significantly decreased the labeling index of colon mucosa during and after AOM treatment. These findings indicate that galanin inhibited the development of colon tumors and that this effect may be related to its suppression of colon-epithelial-cell proliferation.
The accuracy of endoscopic ultrasonography (EUS) for diagnosis of pancreatic cancers was evaluated in consecutive 232 patients with possible pancreatic cancer, and that for assessment of their locoregional spread was evaluated in 28 patients with pancreatic cancer subjected to pancreatectomy, in comparison with the accuracies of transabdominal ultrasonography (US) and computed tomography (CT). EUS was found to be significantly more accurate than US or CT and was especially useful for detecting small pancreatic cancers of less than 2 cm in diameter. With EUS, pancreatic cancers could be detected as a hypoechoic mass with a relatively unclear margin and irregular internal echoes. EUS was also more sensitive than CT and US for detecting venous and gastric invasions: it was more useful for detecting direct invasion of pancreatic cancers when the tumors were less than 3 cm in diameter. These findings indicate that EUS is an accurate method for diagnosis of pancreatic cancer and assessment of their locoregional spread and is particularly useful for detecting small tumors.
The effects of amiloride on the incidence and histology of colon tumors induced by azoxymethane, on the labeling index of the colon mucosa and on the activity of ornithine decarboxylase in the colon wall were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body wt azoxymethane and s.c. injections of 5 or 7.5 mg/kg body wt amiloride in depot form every other day for 35 weeks. Prolonged administration of amiloride at a dose of 7.5 mg/kg, but not 5 mg/kg, significantly reduced the incidence of colon tumors at week 35. However, administration of amiloride had little or no significant influence on the histological types of colon tumors and cancers. Administration of amiloride at 7.5 mg/kg significantly decreased the labeling index of the colon mucosa and ornithine decarboxylase activity in the colon wall during and after administration of azoxymethane. These findings suggest that amiloride inhibits development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by amiloride is its suppression of proliferation of colon tumor cells.
The effects of combined administration of NaCl and the ornithine decarboxylase (ODC) inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the ODC activity of the gastric wall and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats were given drinking water with or without 2.5 g/l DAP and chow pellets with and without 10% NaCl ad libitum after 25 weeks of oral administration of MNNG. At week 52 feeding 10% NaCl resulted in significant increases in the incidence of gastric cancers, in the ODC activity of the antral portion of the gastric wall and in the labeling index of antral epithelial cells. Administration of both NaCl and DAP significantly reduced the enhancements by NaCl of gastric carcinogenesis, ODC activity of the antral wall and the labeling index of antral epithelial cells. These results suggest that inhibition of ODC attenuates NaCl enhancement of gastric carcinogenesis and that enhancement by NaCl of gastric carcinogenesis is mediated by polyamine biosynthesis.