Susumu Taguchi

A Cooperative Randomized Study on Tegafur plus Mitomycin C versus Combined Tegafur and Uracil plus Mitomycin C in the Treatment of Advanced Gastric Cancer

A randomized controlled trial involving 13 institutions in Japan was conducted in order to compare the efficacy of tegafur plus mitomycin C (MMC) (Regimen A) and UFT (a combination of uracil and tegafur at a molar ratio of 4 to 1) plus MMC (Regimen B) for patients with advanced gastric cancer, who had not received any prior cancer chemotherapy. Regimen A (tegafur+MMC) consisted of 5 mg of MMC/m2/week given intravenously, and 500 mg of tegafur/m2/day given orally. Regimen B consisted of the same schedule of MMC and 375 mg of UFT/m2/day given orally. One hundred and eighty‐six patients with primary gastric cancer were entered; 183 were eligible and 3 were ineligible for the study. A total of 169 were evaluable for efficacy of the treatment, including 90 patients with Regimen A and 79 with Regimen B. A response rate of 7.8% (7/90 cases) for Regimen A and one of 25.3% (20/79 cases) for Regimen B were obtained, indicating a significantly higher response rate for Regimen B according to the Criteria for Evaluating Efficacy of Chemotherapy /Radiation Therapy in the Treatment of Gastric Cancer (P= 0.004), Regarding side effects, no marked differences in either severity or incidence were observed between the two groups. The group assigned to Regimen B showed a significant survival advantage after adjustment for major prognostic factors using a proportional hazards model (P=0.0398). Moreover, a close correlation of antitumor effect and survival duration was found when the above criteria were used.

Do Vascular Lesions and Related Risk Factors Influence Responsiveness to Donepezil Chloride in Patients with Alzheimer’s Disease?

The purpose was to identify vascular influences on the responsiveness to donepezil chloride. The study included 50 untreated probable Alzheimer’s disease patients with the Modified Hachinski Ischemic Score <4. We assessed baseline cognitive status using the Revised Hasegawa Dementia Scale (HDS-R), Clinical Dementia Rating (CDR) and the clock drawing test (CDT). The response to 5 mg of donepezil was monitored by the CDT for 12 months. Patients were classified as true responders (TR), unchanged (UC) and non-responders according to changes on the CDT in response to treatment. High HDS-R scores, low CDT scores, low CDR and presence of hypertension (HBP) and periventricular hyperintensities (PVH) predicted a TR- or UC-type outcome. Aggravation of executive function by HBP and/or PVH and its improvement by donepezil may have been detected by the CDT.

Esophageal carcinoma with high serum parathyroid hormone-related protein (PTHrP) level.

Abstract: We report two patients with esophageal carcinoma with high levels of serum parathyroid hormone-related protein (PTHrP). Patient 1 was a 66-year-old man in whom the serum calcium level was also high, and patient 2 was an 81-year-old woman. The serum PTHrP level was 411 pM (normal range, 13.8–55.3 pM) in patient 1 and 94.5 pM in patient 2 (in whom the serum granulocyte colony-stimulating factor level was also high). We demonstrated PTHrP immunohistologically in esophageal carcinoma cells in both patients. After admission, patient 1 died of pneumonia on the 17th day of hospitalization (the 48th day after he had had an episode of frequent hiccuping) and patient 2 died of acute circulatory failure on the 12th day of hospitalization (the 25th day after she had vomited after a meal). Neither of these patients died of cancer. Pneumonia in patient 1 was believed to be due to weakened body defenses, while the acute circulatory failure in patient 2 was due to emaciation. Since esophageal carcinoma with humoral hypercalcemia of malignancy and leukocytosis is characterized by rapid progression and metastasis, early diagnosis and treatment are mandatory.

Inhibitory effects of the cholecystokinin antagonist loxiglumide on pancreatic exocrine secretion and pancreatic growth in conscious rats

SummaryThe effects of cholecystokinin (CCK) receptor antagonist Loxiglumide (CR 1505) on pancreatic exocrine secretion and growth stimulated by chronic bile-pancreatic juice diversion to the ileum were studied in conscious rats. Pancreatic secretion was measured each day at 0900 h for 7 d. Pancreatic flow and protein output were significantly increased 24 h after bile-pancreatic juice diversion. Protein output increased each successive day, reaching maximal values of 3.6-fold above basal by the 6th and 7th d of chronic bilepancreatic juice diversion. Fluid output reached maximal values of approx 3.5-fold above basal by the 3rd d of chronic bile-pancreatic juice diversion. Plasma CCK increased threefold above basal levels after 24 h of bile-pancreatic juice diversion and remained three- to fourfold above basal. Intragastric bolus infusion of CR 1505 (50 mg/kg) on the 7th d of chronic bile-pancreatic juice diversion inhibited pancreatic protein and fluid secretion by 80 and 75%, respectively, 60 min after administration and by 52 and 71%, respectively, 5 h later. Pancreatic wet wt after 7 d of chronic bile-pancreatic juice diversion was significantly increased by 56%, and this was completely suppressed by 50 mg/kg of CR 1505 given intragastrically every 12 h. These rests indicate that the rat with chronic bile-pancreatic juice diversion is a useful model to examine both potency and duration of the action of CCK receptor antagonists and show that CR 1505 inhibits pancreatic exocrine secretion and growth induced by endogenous CCK.

Comparison of oral falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism: a randomized, crossover trial.

BACKGROUND Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral falecalcitriol treatment with those of intravenous calcitriol treatment. METHODS Twenty-one patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. RESULTS Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, -200.1 +/- 107.0 with falecalcitriol vs. -200.8 +/- 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, -137.1 +/- 73.1 with falecalcitriol vs. -120.4 +/- 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral falecalcitriol treatment did not change any bone metabolic marker level. CONCLUSION The present study showed that oral falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.

Effects of 22-Oxacalcitriol and Calcitriol on PTH Secretion and Bone Mineral Metabolism in a Crossover Trial in Hemodialysis Patients With Secondary Hyperparathyroidism

Abstract:  The purpose of this crossover comparison study is to elucidate the differences between the effects of a novel calcitriol analog, 22‐oxacalcitriol, and calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty‐three patients with moderate to severe SHPT were included in a random 2 × 2 crossover trial with two vitamin D analogs (12 weeks for each treatment). Two patients withdrew during the run‐in period for personal reasons. Serum electrolyte, bone metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured periodically. The primary endpoint measure was a decrease in serum iPTH level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH and wPTH levels by similar degrees. Serum Ca, P, and Ca × P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. 22‐Oxacalcitriol significantly decreased the levels of bone metabolic markers, namely, bone‐specific alkaline phosphate, intact osteocalcin, pyridinoline, and cross‐linked N‐telopeptide of type I collagen, after a 12‐week treatment. In contrast, calcitriol did not change any of the levels of bone metabolic markers. The present study showed that 22‐oxacalcitriol is equally effective for PTH suppression, and Ca and P metabolism. In addition, 22‐oxacalcitriol might have putative actions on bone remodeling independent of its PTH suppression. Further study is necessary to confirm the effects of 22‐oxacalcitriol on bone metabolism in SHPT.

Hyperamylasemia and S-type isozyme dominance in liver cirrhosis

SummaryTo investigate the mechanisms of serum amylase abnormalities in liver disease, we determined serum amylase levels, S-type isozyme proportion, clinical symptoms, and laboratory data in 38 cases of histologically confirmed liver cirrhosis and 19 controls. Of the 12 patients who were hyperamylasemic (12/38, 32%), 5 showed S-type isozyme dominance (5/12, 42%), whereas in the 26 normoamylasemic cirrhosis patients, only 5 were S-type isozyme dominant (5/26, 19%). Isozyme percentages were significantly higher (P<0.01) in the dominant-S-type cases than in the controls, and S-type dominance was found more frequently in the hyperamylasemic than in the normoamylasemic cirrhosis cases. Only ascites and esophageal varices were observed more frequently as clinical symptoms in the dominant-S-type cases. Our results suggest that amylase is not produced in the human liver, but that the decreased clearance rate of amylase, especially the S-type isozyme, may be a cause of hyperamylasemia and S-type isozyme dominance in cirrhosis.

Cystic β2-microglobulin amyloidoma in a patient on long-term hemodialysis

We report a patient with β2 microglobulin amyloidosis (β2M) in whom cystic tumors were seen in the bilateral axillary region. The patient was a 68-year-old woman who had been on hemodialysis for more than 20 years because of IgA nephropathy. Computed tomography-guided biopsy was performed to confirm the diagnosis. Congo red staining, β2M immunohistochemistry, and electron microscopy examination of the biopsied sample showed extended β2M deposits in the cystic tumor. β2M-related amyloidosis in patients with long-term dialysis commonly presents as osteoarticular disease, although a soft-tissue pseudotumor, known as amyloidoma, has been reported. This is the first report in the English-language literature of amyloidosis presenting as bilateral axillary cystic tumors.

Reduced reactivity of pancreatic exocrine secretion in response to gastrointestinal hormone in WBN/Kob rats

Abstract: We compared pancreatic exocrine secretion in 5-month-old WBN/Kob rats, a model of chronic pancreatitis, with that in Wistar rats of the same age in a conscious state. Basal pancreatic secretion and pancreatic wet weight in WBN/Kob rats were lower than the values for Wistar rats. There was no difference in plasma cholecystokinin (CCK) concentration between the two types of rats. When CCK-8 was intravenously administered, the stimulation of pancreatic protein secretion in WBN/Kob rats was weaker than that in Wistar rats. When bile and pancreatic juice were diverted from the duodenum, the resulting increase in the plasma CCK concentration was similar in both types of rats, but stimulation of the volume and protein output of pancreatic juice in WBN/Kob rats was weaker than that in Wistar rats. In addition, WBN/Kob rats exhibited little increase in pancreatic wet weight because of this diversion. When secretin was intravenously administered, the stimulation of fluid secretion in WBN/Kob rats was also weaker than that in Wistar rats. The binding of CCK-8 to pancreatic membrane fractions in WBN/Kob rats was much weaker than that in Wistar rats. Histological findings in WBN/Kob rat pancreas showed proliferation of fibrous tissue and atrophy of acinar cells. In conclusion, pancreatic exocrine secretion in response to the gastrointestinal hormones, CCK and secretin, was lower in WBN/Kob rats than in Wistar rats. These findings suggest that the hyposecretion of pancreas in WBN/Kob rats is hyporeaction of pan-creatic membrane to gastrointestinal hormones.

Requirement of the glycosyl parts in platycodin D to stimulate pancreatic exocrine secretion.

The whole structure of platycodin D is found to be essential to stimulate the volumetric increase in the pancreatic exocrine secretion, while the prosapogenins prepared from platycodin D increased only protein output of pancreatic juice.