Effects of Proteolytic Enzyme Inhibitors on the Nasal Absorption of Vasopressin and an Analogue

Proteolytic enzyme inhibitors were examined as absorption enhancers for the nasal delivery of vasopressin (AVP) and desmopressin (l-d-8-DAVP) in rats. Aprotinin, soybean trypsin inhibitor, and camostat mesilate were used as enzyme inhibitors. The nasal absorption of AVP and l-d-8-DAVP was evaluated by measuring its antidiuretic effect. Nasal administration of AVP (0.005 IU/kg) or l-d-8-DAVP alone (2.5 ng/kg) produced a small antidiuretic effect. Coadministration with aprotinin (1000 and 10000 KIU/kg) or soybean trypsin inhibitor (1.25 and 6.25 mM) did not change the antidiuretic effect. However, coadministration with camostat mesilate (1 to 50 mM) significantly increased the antidiuretic effect and, thus, the nasal absorption of AVP and l-d-8-DAVP. The activities of aminopeptidase, cathepsin-B, and trypsin in the nasal mucosal tissue of rats were 7 nmol/min/mg protein, 0.7 nmol/min/mg protein, and 4.6 pmol/min/mg protein, respectively. Aprotinin and soybean trypsin inhibitor inhibited only the trypsin activity, whereas camostat mesilate inhibited aminopeptidase and trypsin activities. Aprotinin (MW 6500) and soybean trypsin inhibitor (MW 8000), with relatively high molecular weights, may not permeate into the nasal mucosal tissue. In contrast, camostat mesilate is slowly absorbed (8%/hr) and could inhibit the proteolytic activity in the nasal mucosa, resulting in enhanced nasal absoprtion of AVP and l-d-8-DAVP.     

Effects of Viscous Hyaluronate–Sodium Solutions on the Nasal Absorption of Vasopressin and An Analogue

The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, l-deamino-8-D-arginine vasopressin (l-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 × 10⁵ daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 × 10⁴ daltons were not effective. The enhancing effects on the nasal absorption of AVP and l-d-8-DAVP were dependent on the concentration in the range of 0–1.5% (w/v) hyaluronate (MW 1.4 × 10⁶ daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and l-d-8-DAVP in hyaluronate solutions (MW 1.4 × 10⁶ and 2 × 10⁶ daltons) increased more than 2- and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 × 10⁶ daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranes in vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and l-d-8-DAVP.     

A Small Gastric Cancer in Association with Menetrier Disease

Abstract: We studied a 57-year-old man who was diagnosed as having giant rugae at a mass-screening for gastric cancer. He was examined endoscopically for check-up purposes. In addition to giant rugal folds which occurred throughout the entire fundus and body of the stomach, a type IIc lesion was noted in the posterior lower wall of the gastric body. A biopsy revealed signet ring cell carcinoma. A total gastrectomy was performed. A resected specimen was serially sectioned and underwent histopathological examination; hypertrophy and cystic elongation of the gastric glands indicative of so-called giant hypertrophic gastritis was seen. The histological type of the type IIc lesion was undifferentiated adenocarcinoma with the signet ring cells being confined to the mucosal layer. This patient had a rare case of Menetrier's disease complicated by intramucosal carcinoma.     

Usefulness of prostate-specific antigen velocity in screening for prostate cancer

BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.     

试论气之原型

将气作为中医的基本概念,是中医界普遍的"常识"。但对其本身的解释与理解已经脱离了它作为掌握人体的媒介的目的,已呈现貌合神离的地步。本文从气功能的角度探讨气的本质与原型。     

Nodule‐aggregating lesion of the ileum: Report of a case and a review of the literature

We describe here a rare case of nodule‐aggregating lesion of the terminal ileum detected by colonoscopy. An 82‐year‐old Japanese woman was admitted to our hospital with diarrhea. Colonoscopy revealed a flat elevated tumor with conglomerated nodular surface involving the entire circumference of the terminal ileum, suggesting a nodule‐aggregating lesion. Magnifying the colonoscopic view showed the branch‐like or gyrus‐like pits. On biopsy, the tumor was diagnosed as a tubulovillous adenoma. Retrograde ileogram using a colonoscope revealed an elevated tumor with nodular irregularity, measuring 5 cm in length. Ileocecal resection was performed. Macroscopically, the tumor in the terminal ileum, 8 cm distant from the ileocecal valve, showed a nodule‐aggregating lesion, measuring 44 × 60 × 6 mm in size. Histologically, the tumor showed a focal carcinoma in tubulovillous adenoma. To our knowledge, this is the fifth case of early cancer of the ileum in Japan, and the first case of nodule‐aggregating lesion of the ileum detected by colonoscopy in the world.     

Frequency of common bile duct motion artifacts caused by inferior vena cava pulsation on magnetic resonance cholangiopancreatography.

PURPOSE: We assessed the frequency of common bile duct (CBD) motion artifacts caused by inferior vena cava (IVC) pulsation on magnetic resonance cholangiopancreatography (MRCP). METHODS: We retrospectively evaluated CBD motion artifacts in 4 MRCP sequences from each of 115 consecutive patients. RESULTS: We observed 37 (32.2%) ghost artifacts at the ventral and dorsal aspects of the CBD on transaxial, half-Fourier acquisition single-shot turbo spin-echo (HASTE-ax) images; no such artifacts were observed on transaxial T(2)-weighted turbo spin-echo images. In 10 patients, we observed 9 (7.8%) pseudo-defects of the CBD on 3-dimensional T(2)-weighted turbo spin-echo with navigator-triggered prospective acquisition correction technique MRCP and 6 (5.2%) pseudo-defects on single-shot rapid acquisition with relaxation enhancement MRCP. Pseudo-defects were significantly more frequent in patients with ghost artifacts than without (9 of 37 [24.3%] versus one of 78 [1.3%]; P<0.01, McNemar test). CONCLUSION: Although uncommon, pseudo-defects of the CBD caused by IVC pulsation are observed on MRCP. MRCP interpretation that includes comparison with HASTE-ax images can diminish the potential misinterpretation of such CBD motion artifact as bile duct tumor or biliary stone.     

The role of percutaneous transhepatic abscess drainage for liver abscess

To evaluate the efficacy of percutaneous transhepatic abscess drainage (PTAD) as an initial choice of treatment for liver abscess, the medical records of 28 patients with liver abscess were retrospectively analyzed. The patients were predominantly men (23 of 28) with a mean age of 59 years (range, 19–86 years). Their chief complaints were fever (86%), right hypochondralgia (32%), and jaundice (11%). Fifteen of the 28 patients (54%) had hepatobiliary and pancreatic carcinoma, and 31% had postoperative liver abscess. PTAD was performed in 23 patients and surgical drainage in 5. The overall success rate for PTAD was 83%. The success rate for PTAD for patients with multiple abscesses was 83% (5 of 6), compared with a success rate of 82% (14 of 17) for patients with solitary abscess. The prognostic factors for survival were cancer and sepsis and the mortality rate for patients with cancer was 40% (6 of 15) while the mortality rate for patients with sepsis was 56% (5 of 9). As a complication of drainage, 1 patient (4%) in the PTAD group had pleural abscess due to the transpleural puncture. Our findings support the use of PTAD as the primary treatment for liver abscess, as it is safe and effective irrespective of the number of abscesses and the patient's condition. Received for publication on Sept. 7, 1998; accepted on Jan. 22, 1998     

The Specificity of the Penetrating and the Superficial Spreading Types of Early Gastric Cancer—Classification of Early Gastric Cancer Using the Interactive Image Analysis System—

Abstract: Specific types of early gastric cancer were investigated in accordance with the cancer surface area and the degree of penetration by means of quantitative measurements of the surface area of early gastric cancer using the interactive image analysis system. The results indicated a significant correlation between the surface area and the penetration depth in ordinary early gastric cancer. However these correlations were not observed in both well and poorly differentiated adenocarcinoma cases of the so-called PEN and SUPER types, which showed a significant specificity when compared with ordinary early gastric cancer. The PEN and SUPER types of early gastric cancer also exhibited various clinicopathological characteristics, and it was suggested that the poorly differentiated PEN type might be the initial lesion of a linitis plastica type gastric cancer. Examination of the conditions of the mucosa surrounding the cancer revealed a difference between the PEN and the SUPER types, and this suggested that the environment at the site of a cancer growth influences the type of growth and the spread of early gastric cancer.