Yasushi Kuyama

Luminal bile regulates cholecystokinin release in conscious rats.

The effects of intraluminal bile on cholecystokinin release and pancreatic exocrine secretion were studied in conscious rats. Since it has been suggested that bile acid may influence pancreatic secretion indirectly by interacting with luminal protease activities, intraduodenal protease activities were eliminated by pancreatic juice diversion accompanied with simultaneous intraduodenal infusion of aprotinin. This treatment resulted in gradual increases in pancreatic juice flow, bicarbonate and protein outputs, and an increase in plasma cholecystokinin levels, reaching plateau levels 2 hr after the start of the treatment. When endogenous bile was excluded from the intestine, the pancreatic secretion and plasma cholecystokinin concentrations further increased. The intraduodenal infusion of sodium taurocholate during bile pancreatic juice diversion inhibited cholecystokinin release, while pancreatic protein output was only transiently decreased. The results indicate that bile in the duodenum directly regulates cholecystokinin release, probably through its major components, bile salts.

No difference in seroprevalences of Helicobacter pylori infection between patients with pulmonary tuberculosis and those without

A previous article reported a possible relationship between a history of tuberculosis and Helicobacter pylori infection. Epidemiologic similarities exist between the two infections: Mycobacterium tuberculosis and H. pylori are transmitted from person to person and the risk of acquiring them is elevated in underprivileged environment. This study was conducted to investigate the relationship between the two infections. Serum concentrations of anti-H. pylori IgG antibody were measured in 40 tuberculosis inpatients on antituberculosis chemotherapy for no more than 3 months (group I; 52.4 +/- 21.4 years of age), 43 tuberculosis inpatients on it for more than 3 months (group II; 57.3 +/- 16.3 years), and 60 nontuberculosis outpatients (control subjects; 55.9 +/- 16.7 years). H. pylori seropositivities were similar among control subjects (73.3%), group I (65%), and group II (69.8%). The difference in the antibody concentrations was significant between control subjects and group I (353.7 +/- 321.2 vs. 176.5 +/- 197.9 U/ml) but was not significant between control subjects and group II (353.7 +/- 321.2 vs. 229.9 +/- 249.5 U/ml). The seroprevalences may not be different between patients with pulmonary tuberculosis and those without, and antituberculosis therapy may not decrease the antibody concentrations.

Pharmacokinetic interaction between acetaminophen and lansoprazole

Because of its minimal gastric toxicity, acetaminophen is the analgesic of choice for patients with gastric acid-related disorders. Because proton pump inhibitors are widely used, concomitant prescription of acetaminophen and lansoprazole would be prevalent. This crossover study was conducted to investigate an acetaminophen-lansoprazole interaction. On one occasion, each of six healthy, fasted, male volunteers ingested 1.0 g acetaminophen dissolved in 200 mL water. On another occasion, at least 1 week apart, 30 mg lansoprazole was administered orally, simultaneously with acetaminophen, after pretreatment with the same dose of lansoprazole once daily for 2 days. Plasma acetaminophen concentrations were measured at 0, 0.25, 0.5, 0.75, 1, 2, 3, 5, and 8 hours after dosing. The peak plasma concentration of acetaminophen and the time to its occurrence were significantly higher and shorter, respectively, during the lansoprazole session than during the control session. Neither the elimination half-life nor the area under the curve was significantly different between the two sessions. Lansoprazole hastens the absorption of acetaminophen solution, but little modifies its elimination rate and bioavailability.

Modified 13C-octanoate breath test and impact of sampling points.

In recent years, the 13C-octanoate breath test has attracted attention as a simple and noninvasive method of assessing gastric emptying of solids. However, practical procedures for test meals, parameters used, and sampling points have not yet been established. Moving toward a more convenient method, here we examined the influences of sampling interval and duration on the 13C-octanoate breath test performed on 15 healthy subjects using a commercially-available instant cupcake. Breath samples were obtained every 15 minutes within 4 hours, and every 30 minutes in the subsequent 2 hours. Using computer simulation, the time it took for the fitting curve to peak (Tpeak) was calculated in each setting with each interval (15, 30, 60, and 120 minutes) and test duration (3, 4, 5, and 6 hours). When the sampling interval widened over 30 minutes, the difference from the original 6-hour data became larger than 20% of the coefficient of variance. When the sampling duration was shortened to 3 hours, no appropriate fitting curve could be achieved. These results suggest that a sampling duration of 4 hours at 30-minute intervals seems to be suitable for practical use of the test.

Urinary Antibody Titers to Helicobacter pylori and an Impact of Clinical Characteristics

This study evaluates the clinical usefulness of titers of antibody to Helicobacter pylori (Hp) in a urine-based enzyme-linked immunosorbent assay (URINELISA; Otsuka Pharmaceutical, Tokushima, Japan) by comparing values of serum antibody to Hp in an already commercialized kit in a population of 250 asymptomatic individuals. Influences of physical and laboratory characteristics on the relationship between serum and urinary titers of antibody to Hp were also estimated using simple and multiple regression analyses. Specific urine gravity, urine pH, proteinuria, and age of the subjects were regarded as significant factors relating to urinary titers of the anti-Hp antibody on simple regression analyses. Both the urinary and serum titers strongly correlated on simple regression analysis (r = 0.782, P < 0.0001). On multiple regression analysis, an additional two factors, specific urine gravity and urine pH, were picked up, and the correlation coefficient was improved (r = 0.795, P < 0.0001). The present results indicate that URINELISA had not only qualitative but quantitative accuracy. However, careful attention should be paid to cases with abnormalities in urinalysis when used quantitatively.

Endoscopic microwave treatment

Endoscopic therapy of gastrointestinal hemorrhage and neoplastic polyps has been practiced widely since the development of high frequency wave probe and snare techniques.! The introduction of the laser modality added another dimension to therapy,2 and since 1980 our department has conducted studies in YAG laser treatment. However, the laser apparatus is expensive, requires eye protection, and risks tissue damage that may be comparatively large. Development of a microwave coagulation apparatus has been undertaken to avoid these drawbacks. A microwave coagulation apparatus developed by Tabuse et a1.,5 produces only a small electrical field, as the microwave is irradiated directly from the tip of the microwave electrode. Thus, the risk of thermal burn is less compared to conventional high frequency waves, where the electric field is less limited. We have evaluated a microwave apparatus as well as its clinical application in endoscopic treatment since January 1983.,7 Thirty-seven cases have been studied thus far. We report here the safety and effectiveness of microwave therapy compared to other treatment modalities.

Synovial sarcoma metastatic to stomach and duodenum

A 49-year-old Japanese man presented witha painful mass on his right calf that was foundby histopathologic and immunohistochemical anal-yses of an open biopsy specimen to be a synovialsarcoma of the monophasic fibrous type. An SYT-SSX1 fusion gene, resulting from the chromosomaltranslocation of t(x;18)(p11.2;q11.2) was detected byreverse transcription polymerase chain reaction.After amputation of his right leg, the patientunderwent chemotherapy and radiotherapy to treatlung metastases. Subsequently, he developed me-lena and was found to be anemic. Upper endoscopydemonstrated multiple protruding lesions with acentral depression in the stomach and duodenum(A,B,C).Freshclotwasattachedtooneofthelesions.Biopsy specimens from one of the gastric lesionsrevealed spindle cell proliferation in the mucosa(D, H&E, orig. mag. 333) that was similar to thesynovial sarcoma from the right calf.

Hepatic Encephalopathy Due to Portal Venous Thrombosis in a Patient with Pancreatic Tumor

To the Editor: Portal venous thrombosis (PVT) is a relatively rare condition in patients with pancreatic tumor that is found incidentally or due to mild hepatic dysfunction in most cases. The coincidence of hepatic encephalopathy is uncommon (1). Here we report on a patient with a pancreatic tumor who developed acute hepatic encephalopathy due to PVT. A Japanese man 84 years of age with diabetes who underwent screening sonography in May 1999 was found to have a hypoechoic mass lesion of the pancreas head, about 2.0 cm in diameter, accompanied by dilatation of the main pancreatic duct (Fig. 1A). Tumor markers, including carcinoembryonic antigen, also showed abnormalities, so the clinical diagnosis of pancreatic cancer was made and radiation therapy was performed (total, 56 Gy). However, tumor markers mildly increased, and the patient gradually became debilitated. In April 2000, he was readmitted to Toranomon Hospital for progressive mental alteration over a 2-day period. He was unconsciousness on admission. There was no icterus at the jugular conjunctiva. The laboratory data showed not only marked dehydration with high glucose concentration (245 mg/dL) but also hyperammonemia (275 g/dL; normal range, <50). Sonography showed occlusion of the portal vein without cavernous transformation and mild ascites (Fig. 1B). The portal trunk had been compressed by the tumor. Serum concentrations of protein S and antithrombin III proved normal, but protein C activity had decreased to 48%. Anticoagulation therapy was not performed because of the patient’s poor general condition. After conservative treatment, the consciousness level was temporarily improved in association with a decline in the serum ammonia level. The general condition gradually became worse, however, and the patient died of biliary tract infection on hospital day 70. Autopsy was not permitted. PVT commonly develops in liver cirrhosis, autoimmune disorders, connective tissue diseases, or disorders involving abnormality of the coagulation system. Presence of a pancreatic mass is regarded as a risk factor for development of PVT because it sometimes compresses the portal vein directly, resulting in a decrease in blood flow, and because tumor cells may invade the portal vein, presenting as tumor thrombus (2). However, portal occlusion develops gradually, and coincidence of hepatic encephalopathy may be infrequent. There have been few previous reports in the literature of hepatic encephalopathy developing in patients with pancreatic tumor (1). In our case, the patient had some predisposing factors for thrombus, including decreased protein C activity, a pancreatic mass, and radiation therapy. In addition, he was severely dehydrated at the time of onset. Therefore, thrombotic occlusion might occur and rapidly progress, inducing hepatic encephalopathy. Here we reported on a rare case of pancreatic tumor in a patient who developed PVT with hepatic encephalopathy. Although such occurrences are infrequent, clinicians who encounter unknown comatose patients should consider the possibility of hepatic encephalopathy and PVT (3).

Pharmacokinetic characteristics of minocycline in debilitated elderly patients.

A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 +/- 6 years. The elimination half-lives at beta-phase averaged 25.0 +/- 16.4 hours, the volume of distribution averaged 32.9 +/- 13.4 L, and the total clearance averaged 1.14 +/- 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54 (P =.06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.

Endoscopic hemostasis techniques for upper gastrointestinal hemorrhage: A review.

Upper gastrointestinal hemorrhage (UGIH) is an urgent disease that is often encountered in daily medical practice. Endoscopic hemostasis is currently indispensable for the treatment of UGIH. Initially, when UGIH is suspected, a cause of UGIH is presumed from the medical interview and physical findings. After ample primary treatment, urgent endoscopy is performed. Many methods of endoscopic hemostasis are in wide use, including hemoclip, injection and thermo-coagulation methods. Although UGIH develops from a wide variety of diseases, such as esophageal varices and gastric and duodenal ulcer, hemostasis is almost always possible. Identification of the causative diseases, primary treatment and characteristic features of endoscopic hemostasis are needed to allow appropriate treatment.