Novel antitumor antibiotics, saptomycins D and E.
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Biomedical subjects
Publications and source records attributed to H Uchida.
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We experimentally investigated the pharmacokinetics of adriamycin (ADM) in a similar of transcatheter arterial chemoembolization therapy (TAE) of hepatocellular carcinoma using emulsion of lipiodol (Lp) mixed with ADM followed by gelatin sponge, and the difference resulting from composition and method of preparation of the emulsion as well as behavior after mesenteric arterial injection in rat. In in vitro study, the emulsion with iopamidol (iopamiron 300 : IP) was more stable than with amidotrizoic acid (60% Urografin : UG). The highest stability was found in the mixing ratio of Lp. IP and distilled water at 1 : 0.42 : 0.08. Frequent pumping also made the emulsion more stable. But in optimally composed emulsion, pumping 20 or 50 times made no difference in the stability during 30 min. which may be longer than the time from preparation to injection time of the emulsion in clinical application. After injection of the emulsion into the mesenteric artery which may simulate injection into the hepatic artery in hepatocellular carcinoma, the arterial blood flow was suspended. In the peripheral arteries the emulsion separated into two phases of Lp and ADM solution, forming striped pattern, and Lp embolization of the peripheral artery persisted for over 45 min. while ADM extravasated. These findings suggest that after Lp-TAE, Lp maintains an embolizing effect while ADM penetrates into the surrounding tumor tissue, and that this is an underlying mechanism for the anti-cancer effect of Lp-TAE.
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The patient had elevated plasma PIVKA-II and serum AFP levels. However, no tumor was detected with an ultrasonography, angiography, abdominal computed tomography (CT), and magnetic resonance imaging (MR). Gastric endoscopic examination disclosed gastric cancer and then subtotal gastrectomy was done. Shortly after the surgery, both plasma PIVKA-II and serum AFP levels returned to each normal level. The extirpated tumor revealed histologically immature and mature cancer cells. It was pathologically diagnosed as IIc early cancer. The localization of PIVKA-II and AFP in gastric cancer cells was demonstrated by the immunostaining method using monoclonal antibody. Taken together, these results indicate that cancer cells may produce PIVKA-II or AFP in this patient.
The anterior capsule was preserved intact in pars plana lensectomy in 14 cases of pars plana vitrectomy carried out for proliferative diabetic retinopathy in 9 cases, sarcoid uveitis in one case, proliferative vitreo-retinopathy in 3 cases and retinal detachment with a giant break in one case. Follow-up periods ranged from 6 to 17 months, with a mean of 11 months. Simultaneous posterior chamber intraocular lens implantation anterior to the anterior capsule was performed in 7 cases, and in one case secondary implantation was performed 4 months later. In 11 cases anterior capsules remained clear and in 9 of them lens epithelial cells had been thoroughly removed up to the equator using a Terry squeegee. Posterior synechia occurred in 4 cases in which air or gas tamponade had been done. This method allows complete anterior vitrectomy and is adaptable not only to simultaneous but also secondary posterior chamber intraocular lens implantation.
Two cases of eosinophilia-associated acute peri-myocarditis which coursed favorably are reported. Case 1 was a 47-year-old man whose ECG revealed QS, ST-T change, bundle branch block, and arrhythmias. Case 2 was a 30-year-old man whose ECG showed ST segment depression. The chest radiographs of both patients revealed enlarged hearts. Left ventriculography showed abnormal regional wall motion. Their endomyocardial biopsies revealed eosinophilic infiltration of the myocardium, but few eosinophils were degranulated. In Case 1, the development of eosinophilia preceded perimyocarditis and the eosinophilia continued even after the symptoms of peri-myocarditis were improved. In conclusion, it seems that eosinophilia did not have specific relation to the initial manifestation of the disease but that it occurred as a secondary reaction to peri-myocarditis of unknown etiology in these cases.
A 53-year-old Japanese woman suffered hypophosphatemic osteomalacia secondary to bone tumor. Her clinical symptoms did not improve for a long time following the oral administration of Alfacalcidol (vitamin D3). A bone survey using radiographs revealed a small tumor located in the proximal head of the left fibula. Hypophosphatemia and low levels of 1-alpha,25-dihydroxycholecalciferol (1-alpha,25(OH)2D3) returned towards normal levels soon after an en-bloc tumor resection, and bone pain and muscle weakness gradually disappeared. The histology, especially of the trabecular bone of the left fibula, showed typical features of osteomalacia with demineralization. The tumor comprised numerous small blood vessels, spindle shaped or oval neoplastic cells, a few multinucleated giant cells, osteoid tissue with or without calcification, chondroid tissue and hemangioma. The spindle shaped or oval cells contained a round nucleus with no mitotic figures. These clinical and histological findings coincide well with a diagnosis of benign ossifying mesenchymal tumor of the bone with vitamin D resistant hypophosphatemic osteomalacia.
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The respiratory and hemodynamic responses to postoperative reversal by naloxone of high-dose fentanyl anesthesia were studied in 101 patients after open heart surgery. Respiratory and hemodynamic changes after drip infusion of naloxone were minimum. Change of systolic blood pressure (BPs), mean blood pressure (BPm), CVP and PO2 were statistically significant. BPs increased for 3.8 +/- 14.0 mmHg, BPm increased for 1.6 +/- 8.2 mmHg. CVP decreased for 0.4 +/- 2.1 mmHg, and PO2 decreased for 8.6 +/- 3.4 mmHg. Severe side effect was not observed. Multi-factorial analysis revealed that the abrupt recovery of consciousness from anesthesia and acidosis were the most important factors that attenuate hemodynamic response to naloxone.
Two cases of massive hemorrhagic shock induced by tracheo-innominate artery fistula are reported. The first case is a 4 year-old girl with encephalitis under prolonged mechanical ventilation. The second case is a 6 year-old tracheostomized girl with mental and motor retardation of congenital origin who has been taken care of at her home. This catastrophic complication is usually caused by long term placement of tracheostomy tube with the cuff inflated especially in malnourished pediatric patients. The cuff pressure is apt to be concentrated on one side of the tracheal wall especially in mechanically ventilated immobilized patients. Although this complication is rare because cuffed tube is currently avoided in pediatric patient, sophisticated care should be taken in managing tracheostomized patients.
Efficacy of intraoperative electron beam radiotherapy (IOER) on N-nitrosobis (2-hydroxypropyl) amine (BHP) induced pancreatic carcinomas transplanted into the pancreas of the Syrian golden hamsters were studied and the following results were obtained. 1. Selective electron beam application to the carcinoma transplanted into the pancreas of hamsters was accomplished using an electron beam collimator. 2. Intra-pancreatic transplantability of BHP-induced serially transplantable subcutaneous pancreatic carcinomas was 100%. 3. Intra-pancreatic transplanted pancreatic carcinomas disappeared in 2 out of 19 hamsters (11%) by 10 Gy irradiation and 7 out of 15 (47%) by 20 Gy irradiation given 2 weeks after intra-pancreatic transplantation. 4. In contrast to the linear growth of tumor size in the non-irradiated group, the tumor size showed an electron dose-dependent reduction in the irradiated group. 5. Histologically, marked necrosis was noted in the irradiated group, and the intensity of necrosis differed between the 10 Gy and 20 Gy groups. 6. Direct invasion of tumor to the stomach, small intestine, large intestine, liver and abdominal wall was noted. Its incidence tended to decrease as the electron dose increased (5/19 or 26% for the control group, 4/19 or 21% for the 10 Gy group, and 1/17 or 6% for the 20 Gy group), although the difference was not statistically significant. 7. The incidences of liver and lymph node metastasis were not different between the non-irradiated and the irradiated groups. These results suggest that selective IOER on BHP-induced pancreatic carcinomas has an effectiveness to kill cancer cells in hamsters.
A toxicokinetic study of norfloxacin-induced arthropathy in juvenile animals was undertaken using nalidixic acid as a standard drug. Norfloxacin and nalidixic acid were subcutaneously administered to rats and rabbits, orally administered to dogs, and norfloxacin was orally dosed to monkeys once a day for 7 consecutive days. Of the dose levels tested, the minimum arthropathic doses of norfloxacin were 100, 25, and 50 mg/kg/day in rats, rabbits, and dogs, respectively. At these doses, the peak serum concentrations (Cmax) on Day 6 were 16.1, 9.73, and 5.11 micrograms/ml, and the areas under the serum concentration/time curve (AUC0----infinity) were 31.9, 22.9, and 26.2 micrograms.hr/ml, in respective animals. Monkeys showed no arthropathy with norfloxacin at doses of less than 500 mg/kg/day, at which the Cmax and AUC0----infinity were 15.6 micrograms/ml and 103 micrograms.hr/ml, respectively. The minimum arthropathic doses of nalidixic acid were 50, 100, and 25 mg/kg/day in rats, rabbits, and dogs, respectively. The Cmax and AUC0----infinity of nalidixic acid were higher than those of norfloxacin in all animals. Joint tissues took up more norfloxacin than nalidixic acid, but when arthropathy was present the articular cartilage concentrations of the two drugs were in the same range. The penetration of norfloxacin into the articular cartilage was the same regardless of the joint's anatomical locations, but differed among species, being highest in rats and lowest in monkeys. The Cmax and AUC0----infinity of norfloxacin in animals at their arthropathic doses were far higher than those measured clinically in children, whereas those of nalidixic acid in animals did not differ much from its clinical parameters.
An effective technique using an Escherichia coli plasmid system was developed to clone fragments of exogenous DNA of as large as 100 kilobase pairs. The characteristic features of this technique are the use of a low copy number (one to two) mini-F based plasmid vector and the introduction of artificial lambda cosR ends into the termini of DNA sources and then of the cosL ends into those of linearized vector molecules. This terminal modification greatly facilitated the formation of active large recombinant molecules, which was rarely achieved when the modification was omitted. The efficiency with which large recombinant clones can be generated is high enough to allow construction of a comprehensive library of higher organisms. All analyses of the plasmids recovered have revealed that the inserts were faithful replicas of the human DNAs used as sources.
Thirty-five complete arterial occlusions of pelvis and extremity in 29 patients were treated with intraarterial urokinase infusion therapy. In 28 limbs, the occlusions were due to arteriosclerotic change and in 7 lesions, the occlusions were due to Burger's disease. The patients with arteriosclerotic change ranged in age from 52 to 84 years with a mean age of 68 years, and the patients with Burger's disease ranged in age from 35 to 47 years with a mean age of 43 years. There were 24 men and 5 women. The estimated duration of the occlusion was from 5 days to 5 years with a mean duration of 11 months. The length of the occluded segments ranged from 1 to 45 cm with a mean length of 13.9 cm. The occlusion was located in the iliac artery in 13 patients, the femoral artery in 11 patients, both the iliac and the femoral artery in 2 patients, the popliteal artery in 5 patients, the femoro-popliteal artery in 1 patient, the brachial artery in 2 patients and the radial artery in 1 patient. The infusion catheter was gently advanced into the proximal portion of the clot over a flexible guide wire, and urokinase was infused at a rate of 5000-10000 IU/min, as a short term high dose infusion (SHI), until antegrade blood flow was reestablished. The catheter was then withdrawn to a point proximal to all of the remaining clot, and the infusion rate was reduced to 10000-20000 IU/h as a continuous low dose infusion (CLI). After thrombolytic recanalization, a percutaneous transluminal angioplasty (PTA) was performed in those cases which demonstrated a residual narrowing of the lumen. The initial success rate was 86%. Reocclusions were observed in 5 lesions (17%) and a second recanalization was successful in 2 of 3 patients. The 1-year cumulative patency rate following recanalization was 88.4% and the 2-year patency rate was 78.6%. No significant complications directly related to the procedure were observed. SHI combined with CLI and PTA appears to be an effective and safe therapy for chronic long segmental arterial occlusion.
In vivo 23Na magnetic resonance images of guinea pig kidney were obtained at 2.1 T using a spin-echo sequence with an echo time of 19 ms. The intact kidney showed a very strong signal intensity in the sodium image. The signal intensity of the kidney decreased to 55% after ligation of the renal artery together with the vein and the ureter. The total sodium content in the excised kidney after arterial occlusion, measured by flame photometry, was 24% higher than that in the intact kidney. The transverse relaxation time (T2) of the extracellular sodium in the isolated kidney decreased to one-third of that in the intact kidney. This shortening of T2 may be partly responsible for the decrease in the 23Na signal intensity from the kidney after arterial occlusion.