Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.     

Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.     

The effect of wedged insoles on the thrust of osteoarthritic knees

Summary. We describe a method of quantifying the lateral/medial thrust of the knee which occurs in the early phase of walking. We have used this method to evaluate the effects of wedged insoles on the lateral and medial thrust for normal knees and knees with unicompartment osteoarthritis (OA). A laterally elevated (valgus) insole decreased the lateral thrust of both normal and osteoarthritic knees. A medially elevated (varus) insole increased the lateral thrust. In 50 symptomatic knees with medial compartment OA, decreasing the lateral thrust with a valgus insole reduced pain on walking in 27. Patients whose pain was reduced by valgus insoles tended to have earlier OA and to have a significantly greater reduction in the lateral thrust than in the 23 remaining unaffected knees. A varus insole was effective in decreasing the medial thrust and reducing pain in all ten knees with lateral compartment OA. We recommend the use of valgus insoles for patients with painful early medial compartment OA and the use of varus insoles for lateral compartment OA.

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Résumé. Les auteurs présentent une méthode d’évaluation quantitative, avec mesure par un accéléromètre, des écarts internes ou externes qui se font au niveau du genou dans la première phase du pas. Ils ont étudié les effets dynamiques et l’utilité clinique des semelles à coin valgisant ou varisant pour les genous atteints d’arthrose unicompartimentale. Une semelle à coin externe (valgisante) diminue l’écart externe ou augmente l’écart interne que subit le genou normal ou arthrosique. L’effet est inverse pour une semelle à coin interne. Sur 50 genoux atteints d’arthrose interne avec écart externe, la semelle à coin valgisant diminue les douleurs à la marche dans 27 cas et est inefficace dans 23 cas. Les genoux pour lesquels les semelles valgisantes sont efficaces ont une réduction significative de l’écart externe par rapport à ceux pour lesquels ces semelles sont inefficaces. La semelle valgisante est plus efficace en cas d’arthrose du genou débutante qu’en cas d’arthrose évoluée. La semelle varisante est active pour les 10 genoux avec arthrose compartimentale externe et écart interne.

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Accepted: 28 February 1996     

A Case of a Patient with a Rectal Ulcer Who Had an Unusual Defecation Habit

Abstract: This case report describes a patient with a rectal ulcer who had an unusual defecation habit. Complete healing was recognized colonoscopically after the patient was instructed to break this habit. A polyp of the ascending colon was detected by a barium enema in a 37-year-old man complaining of anal bleeding. He was admitted to our division to undergo a polypectomy. At the time of the polypectomy, a round ulcer, measuring 1 cm in diameter, was detected on the right wall of the rectum 3 cm from the anal verge. A diagnosis of mucosal prolapse syndrome of the rectum could not be made because the patient did not exhibit the characteristic habit of excessive “straining” mentioned by patients with this syndrome, and no characteristic finding of fibromuscular obliteration was found on histological examination of biopsied specimens taken endoscopically from the lesion. Repeated history taking, however, revealed that the patient had the unusual habit of inserting his finger into his rectum after defecation. He broke this habit following instruction to do so. As a result, on colonoscopic examination 15 month later, the ulcer was found to have become a scar:     

Desmoid tumor of the abdominal wall preoperatively suspected as urachal tumor: a case report]

A case of desmoid tumor of the abdominal wall which was preoperatively suspected as urachal tumor is presented. The patient was a 56-year-old man, who was referred to our clinic for further examination of the mass detected incidentally in the ventral region of the urinary bladder by computed tomography. Ultrasonography showed that the mass had a heterogenous and hypoechogenic content. An urachal tumor was suspected and surgery was performed to remove the tumor. During the operation we found that the tumor was completely separated from the urinary bladder and that it had originated from the left rectus abdominal muscle. The pathological diagnosis was desmoid tumor of the abdominal wall. Since urachal tumor has no characteristic findings on the imaging examinations, it is difficult to differentiate desmoid tumor of the lower abdominal wall from urachal tumor, preoperatively.     

Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation.

We used the Gorog Thrombosis Test to analyze the factors influencing the occlusion time, which represents platelet activation and subsequent occlusive thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean age, 45.0 +/- 12.0 years). The Gorog Thrombosis Test was designed to evaluate platelet aggregation and thrombolytic activity under a high shear stress condition (175 dynes/cm) in a native blood sample in vitro. The mean +/- SD occlusion time was 154.8 +/- 64.7 s (men, 153.4 +/- 64.2 s and women, 165.4 +/- 56.5 s). The occlusion time was inversely correlated with von Willebrand factor ristocetin cofactor activity (VWF:Rco) (r = -0.242, P = 0.0055) and von Willebrand factor antigen (r = -0.230, P = 0.0080). The mean occlusion time in the group with VWF:Rco of at least 170% (137 s) was significantly shorter than that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts, other coagulation markers and smoking showed no significant correlations with occlusion time. Red blood cells (r = -0.177, P = 0.0365), hemoglobin (r = -0.191, P = 0.0245) and hematocrit (r = -0.182, P = 0.0329) also showed inverse correlations with the occlusion time. This report is the first to clearly demonstrate the role of von Willebrand factor in the formation of occlusive thrombi in the Gorog Thrombosis Test.     

The relationship between histopathological findings in oral squamous cell carcinoma and FDG uptake on PET

Objectives It is known that, in fluorine-18 fluorodeoxyglucose Positron Emission Tomography (FDG PET) for the diagnosis of oral cancer, FDG uptake may vary even among different cases of the same squamous cell carcinoma. However, the details of this phenomenon have not yet been elucidated. In this study, we analyzed the relationship between histopathological findings in oral squamous cell cancer and PET findings on FDG uptake. Methods We examined 45 patients with oral squamous cell carcinoma who had undergone FDG PET before treatment. FDG uptake was assessed by a standardized uptake value (SUV) calculated according to the PET-measured tissue concentration of FDG, the administered dose of radionuclide, and the body weight of the patient. The relationship between the mean SUV and each of the following parameters was examined: histological grade of malignancy, degree of cell differentiation, size and/or local extent of the primary lesion, and cell density of the tumor. Results The mean SUV of FDG uptake did not depend on the histological grade of malignancy or on the degree of cell differentiation, but tended to be greater the larger the primary lesion. SUV also depended on cell density, increasing with the percentage of tumor parenchyma. Conclusions It is concluded that cancer cell density greatly influences the SUV of FDG, in that a tumor with fewer cellular elements in cancer tissue tends to become a false negative.     

MULTICENTER STUDY DESIGN OF THE EX VIVO EVALUATION OF ENDOCYTOSCOPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Optical technological innovations enable us to visualize cellular nuclei endoscopically. Herein is described a protocol design for a multicenter study for the ex vivo evaluation of endocytoscopy. The present study was performed by the Endoscopy Forum Japan study group.