Clinical phase I study of T-2588

A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses.     

A case report of inflammatory breast cancer effectively treated with cis-platinum

A 50-year-old woman with bilateral inflammatory breast cancer (T4, N1b, M1, Stage IV) underwent right extended radical mastectomy and left modified radical mastectomy following pre-operative administration of carcinostatics (ADM, 5-FU) and irradiation. However, tumor recurrence was observed at the skin and right pleural cavity after the operation. Adriamycin-containing combination chemotherapy and radiation therapy were performed, but no significant response was obtained. CDDP was then administered intravenously at a daily dose of 62.5 mg/m2 at intervals of 60 days. The pleural effusion disappeared and the extent of skin metastasis was reduced, resulting in partial response which lasted for 90 days. The serum CEA level decreased from 13.1 ng/ml to 2.3 ng/ml. As the side effects of this therapy, slight nausea, vomiting and general fatigue were observed. This result suggested that CDDP is an effective drug for inflammatory breast cancer.     

Role of red blood cell deformation in toxicity of contrast media in cerebral angiography

The authors investigated the effect on the brain of red blood cells that had been modified by contrast media. Rat blood was mixed with an equivolume of contrast media, and up to 200 microL of the mixture was infused to the internal carotid artery of the rat. Evans blue was administered intravenously to assess the integrity of the blood-brain barrier (BBB). Immediately after the death of the animal, or 2.5 hours after the infusion, the brain was removed for evaluation of the degree of BBB destruction and edema. Extensive destruction of the BBB, cerebral edema, and death of the animals were induced by infusion of blood mixed with an ionic contrast medium, such as diatrizoate and iothalamate, which deformed red blood cells. Microscopic observation showed atrophy and necrosis of nerve cells and decomposition of nerve fibers in the affected area of the brain. Cerebral damage was not observed in rats injected with blood mixed with a nonionic contrast medium such as iopamidol, iopromide, or metrizamide, which had less effect on red blood cells. Cerebral damage also was observed in the rats injected with blood mixed with a hyperosmotic solution of mannitol, as well as washed red blood cells mixed with an ionic contrast medium. This study's results indicate that hyperosmotic ionic contrast media affect red blood cells and cause disturbance in cerebral circulation.     

Klinische Erfahrungen mit der Knorpel-Knochen-Transplantation

The treatment of deep cartilage defects in load-bearing joints is a problem that still has no satisfactory solution. Full-thickness defects of the articular cartilage rarely heal spontaneously, usually leaving damage that can lead to early arthrosis. Techniques currently available for the treatment of chondral defects include abrasion, drilling, micro-fracturing, transplantation of tissue autografts and allografts, and cell transplantation. Osteochondral autograft transplantation is currently the only surgical cartilage repair technique known to lead to the formation of genuine hyaline articular cartilage and its retention at least in the medium term. The Draenert method, in which a water-cooled diamond bone-cutting system is used, is an effective procedure for resurfacing the joints affected by localised cartilaginous defects, even when there is also severe bone loss. Donor-side morbidity can be kept to a minimum by filling the defect caused by harvesting with a press-fit cylinder of cancellous bone covered with periosteum for protection.     

The concept of culture: A core issue in health disparities

Contemporary discourse contains numerous examples of use of the concept of culture by social and behavioral scientists. Simple reification, where the speaker makes culture into a thing capable of action exemplifies one usage in public discourse. Some quantitative social scientists attempt to characterize people’s cultural identities by means of a single categorical variable, which often “lumps” people into categories such as “Hispanic” or “Black” that in fact have numerous culturally bounded subcategories. Approaches that emphasize cultural process are preferable to those who attempt to categorize; more complex measures of acculturation help investigators to make convincing analyses of circumstances in which health disparities occur. Examples in which investigators make appropriate use of cultural characterizations demonstrate their utility in investigating health disparities in Haitian American women, injecting and noninjecting drug users, Hispanic youth, and adult Hispanics at risk of HIV infection. Focus on culture in the study of health disparities can identify entanglements between structural factors such as poverty and lack of education and cultural factors such as beliefs about health. Qualitative methods coupled with quantitative methods have great potential to improve investigators’ grasp of cultural nuance while capturing the distribution of qualitatively derived behaviors.     

Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing.