Influence of concurrent and staggered dosing of semi-solid nutrients on the pharmacokinetics of orally administered carbamazepine in rats.

In the present study, we examined the effects of concurrent and staggered dosing of PG-soft ace-MP TM (PG), novel semi-solid enteral nutrients, on the pharmacokinetics of orally administered carbamazepine (CBZ) in rats due to the high possibility of drug interaction during the absorption process. The pharmacokinetic behavior of CBZ was considerably altered when administered concurrently with PG. The maximum serum CBZ concentration (Cmax) significantly decreased and the mean residence time (MRT) significantly increased. The elimination constant (ke) also significantly increased, but there were no significant changes in the area under the serum CBZ concentration versus time curve (AUC) and the time to reach Cmax (Tmax). However, these changes in the pharmacokinetic parameters were eliminated by waiting 20 min, the time interval equivalent to the Tmax described above, between CBZ administration and PG dosing. This study suggested that PG interferes with CBZ absorption from the digestive tract, although staggered administration of CBZ and PG prevented their interaction.

Clinical manifestations of Takayasu arteritis in India and Japan--new classification of angiographic findings.

In this retrospective review 102 Indian and 80 Japanese patients with Takayasu arteritis were compared in regard to their clinical manifestations and angiographic findings. Regardless of nationality, most patients were initially affected in their teens or twenties. Japanese patients were female in a larger ratio compared with the ratio in India. Clinically, the two groups exhibited several different features. More Japanese patients were found to be pulseless (P < 0.01) whereas many Indian patients were hypertensive (P < 0.01). Inflammatory conditions in Japanese patients were more severe (P < 0.01) and tended to be more prolonged than those in the Indians. More Japanese patients suffered from aortic regurgitation (P < 0.01), but Indians suffered from hypertension (P < 0.01). Angiographic findings revealed that the aortic arch and its branches were mainly involved in Japanese patients (type I, IIa) whereas the abdominal aorta and its branches were mainly involved in Indian patients (type IV). However, the diffusely involved type (type V) was the one most commonly found in both countries. From the analyses of vascular lesions in both Indian and Japanese patients, 510 and 396, respectively, different progressions of vasculitis are speculated. In Japanese patients, vasculitis generally occurs in the ascending aorta, the aortic arch, and/or its branches and extends into the thoracic and abdominal aorta, subsequently forming various complicated lesions with prolonged inflammatory activity. On the other hand, in Indian patients, vasculitis generally occurs in the abdominal aorta involving renal arteries, subsequently extending into the thoracic aorta within one or two decades, simple vascular lesions being formed. Data analysis suggests that this morbid condition progresses differently in India and Japan, in spite of some common etiologic factor(s).

[Clinical analysis of adjuvant chemotherapy using 5-fluorouracil, leucovorin and cis-diamminedichloroplatinum for patients with advanced and recurrent gastric cancer].

The chemotherapy combining 5-FU, CDDP, and LV was conducted in 17 patients with advanced and recurrent gastric cancer. The regimen consisted of 5-FU (by continual infusion 600 mg/m2/day for 5 days), CDDP (low-dose consecutive drip infusion, 2 hours 20 mg/m2/day for 3 days) and LV (by bolus infusion 20 mg/ m2/day for 5 days). Advanced gastric cancer was found in 12 cases (operation performed in 9 cases and 7 cases resectable) and recurrent in 5 cases. Macroscopic judgment of efficacy in 10 recurrent and inoperable cases revealed CR in 1 patient, PR in 5 patients, NL in 2, and PD in 2 patients. The overall response rate was 60.0%. There were 7 resectable cases, 4 PR patients, 1 MR and 2 NC patients. The overall response rate was 57.1%. Operations were done in 9 of 12 patients with advanced gastric cancer. The histological effects in 7 cases with resectable cases were as follows: 1 patient of grade 0, 2 patients of grade 1a, 3 patients of grade 1b, and 1 patient of grade 2. The main adverse reactions were gastrointestinal symptoms, but in 3 cases thrombocytopenia was found. This chemotherapy for advanced and recurrent gastric cancer shows excellent clinical efficacy.

[Efficacy of combination chemotherapy with mitoxantrone, vincristine, doxifluridine and prednisolone for recurrence of breast cancer].

We treated fifteen patients with recurrent breast cancer by a combination of mitoxantrone (8 mg/m i.v., day 1), vincristine (1.2 mg/m i.v., day 1), doxifluridine (800 mg/body po, everyday) and prednisolone (30 mg/body po, day 1-7). Cycles were repeated every 3 weeks and all patients received more than 2 cycles. A response to treatment was observed in 9 of 15 evaluable patients (60.0%) with 4 complete remissions and 5 partial remissions. Eight patients were previously exposed to anthracyclines. In 5 of 7 cases with no previous chemotherapy, treatment was effective, and in 4 of 8 cases previous chemotherapy was effective. The toxicity was primarily leucopenia (86.7%), and 9 patients received G-CSF therapy. Other toxicities (alopecia, neurologic and general fatigue) were mild. Two patients with heart failure were recognized and treated with other therapy. This chemotherapy is effective for the treatment of recurrent breast cancer.

Angiographic findings of Takayasu arteritis: new classification.

Having proposed a new classification on angiographic findings of patients with Takayasu arteritis, we evaluated the angiographic findings of 80 Japanese patients and 102 Indian patients according to this classification. Japanese patients showed a higher frequency of involvement of the ascending aorta, aortic arch and its branches than did the Indians (P < 0.01). On the other hand, the frequency of involvement of the abdominal aorta and/or renal arteries was higher in Indian patients (P < 0.01). Type III cases of the new classification which involves the thoracic descending aorta, abdominal aorta and/or renal arteries were observed in 3% of the Indian patients, but not at all in the Japanese. In conclusion, in Japanese patients, vascular lesions tend to occur primarily in the ascending aorta, aortic arch and/or its branches and extend into the abdominal aorta. On the other hand, in Indian patients, the tendency is primarily in the abdominal aorta including renal arteries and extending into the thoracic aorta.

[A case report of an advanced esophageal carcinoma treated by neoadjuvant chemotherapy (CDDP + 5-FU) and evaluation of effect on metastatic lymph nodes].

A 69-year-old woman was diagnosed to have type 2 advanced esophageal carcinoma measuring Im 9 cm by X-ray and endoscopic examination. CT scan revealed much swelling of No. 106 and 9 lymph nodes. As the patient had dry cough and these lymph nodes, we tried neoadjuvant chemotherapy for reduction of metastatic lymph nodes. The regimen consisted of CDDP 80 mg/m2 (day 1), 5-FU 800 mg/m2 (day 1-4, continuous). After 2 courses, an operation was performed. Histopathological examination of the section of the primary tumor revealed that only a few cancer cells nests (sq. c.c., mod.) remained in the muscle layer. In 41 dissected lymph nodes, 12 lymph nodes had metastatic cancer cell nests before neoadjuvant chemotherapy and only 4 lymph nodes had a few remaining cancer cells nests. The effect of CDDP + 5-FU therapy is the same for primary tumor and lymph nodes.

Comparative studies between Japanese and Korean patients: comparison of the findings of angiography, HLA-Bw52, and clinical manifestations.

A Japan-Korea cooperative survey on Takayasu arteritis has shown some differences in the features between Japanese and Korean patients with this disease. In angiographic findings, Japanese patients more frequently had lesions at the aortic arch and/or its branches (58% of 75 cases), while, in Korean patients, the abdominal aorta is the site of relatively frequent lesions (30% of 112 cases). Higher occurrence of HLA-Bw52 was found in Japanese patients in comparison with Korean patients (46% vs 15%). The presence of HLA-Bw52, however, might have a close association with Takayasu arteritis in Korea as well as in Japan. The complications in 126 Japanese and 88 Korean patients were also compared. The complications occurring with higher frequency in Japanese patients were aortic regurgitation, ischemic heart disease, and visual disturbances, while, in Korean patients, the more frequent complications were renovascular hypertension as well as hypertension of some other etiology.

Pregnancy in Takayasu arteritis from the view of internal medicine.

To evaluate the influence of pregnancy on the morbid condition of Takayasu arteritis, we summarized the clinical data and pregnant courses of 18 patients with Takayasu arteritis and a total of 22 deliveries. We followed C-reactive protein (CRP) scores in 16 of 18 patients (20 of 22 deliveries) to ascertain the inflammatory condition inherent in Takayasu arteritis 1 year prior to, during, and 1 year after pregnancy. We also evaluated digital plethysmograms (pulse amplitude, pulse wave, crest time) to follow the hemodynamical condition of patients before, during, and after pregnancy. CRP scores improved significantly during pregnancy and 1 year after delivery. In the digital plethysmograms, pulse amplitude and wave also exhibited improvement after delivery, but crest time remained unchanged. This indicated that pregnancy is a state favorable to this disease. Some factors, such as the sex hormone progesterone, may induce this condition, but the details are still unknown. In conclusion, inflammatory activity and the hemodynamic state improve with pregnancy in patients with Takayasu arteritis. The physiologic aspects which cause this improvement should be maintained even after pregnancy.

Takayasu arteritis: follow-up studies for 20 years.

We reviewed retrospectively 126 (5 male, 121 female) patients suffering from Takayasu arteritis who had been treated in our clinics from 1971 to 1990. The patients' ages ranged from 19 to 80 yrs old (1990) with a mean age of 48.7 +/- 11.8 years. HLA typing analysis in 98 patients revealed that 45 patients (47%) were confirmed as carrying the Bw52 antigen, a high result that is statistically significant as compared with that in healthy Japanese. Arteriograms (performed in 75 patients) revealed that 28 patients (37%) were affected in the aorta and its main branches by this disease (type IV by Nasu's classification) and 23 patients (31%) were affected only in the main branches (type I). The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved significantly from 2.55 +/- 0.28(+) and 57.0 +/- 5.69 mm/hr to 0.53 +/- 0.12(+) and 31.2 +/- 3.45 mm/hr, respectively after treatment including steroid and antiplatelet therapy (P < 0.01). Patients with Bw52 exhibited more severe inflammatory conditions than those without Bw52. Lung scintillations performed in 81 patients showed pulmonary arterial lesions in 50 patients (62%). Echocardiograms revealed aortic regurgitation (AR) in 44 patients (35%), with a significant difference noted between the Bw52 positive group and the Bw52 negative group [29/40 (73%) versus 11/47 (23%), respectively, P < 0.001]. Patients with Bw52 were prescribed higher doses of steroids (P < 0.05) for longer periods (P < 0.01) than those without Bw52.(ABSTRACT TRUNCATED AT 250 WORDS)