Development of total artificial heart with economical and durability advantages.

To develop a total artificial heart (TAH) pump system, we created a design paying particular attention to durability and cost. We adopted a pneumatically driven sac type artificial heart, where the configuration of the sac was decided according to the methodology of flow visualization. Its configuration is almost round to achieve as little stagnation as possible and a low turbulent flow. The main body of the sac was made using polyvinyl chloride (PVC) paste. The paste was poured into an external mold, and heated in a hot air drying oven. Coating was performed using polyurethane. The basic performance of this pump system was tested using a model circulation circuit, and a fitting study through acute animal experiment, using a healthy adult goat, was carried out. As for the TAH produced experimentally, a pump output exceeding 5.0 l/min in the model circulation circuit was provided. Implantation in the internal pleural cavity of a healthy adult goat, 55 kg in weight, proved possible and quite easy in comparison. It is thought that a more refined design in the connector part is desirable. Furthermore, a chronic experiment with the TAH will be carried out, and examination will need to be repeated in the future.

Drastic genetic instability of tumors and normal tissues in Turcot syndrome.

Turcot syndrome is characterized by an association of malignant brain tumors and colon cancer developing in the patient's teens. Since the mechanism of carcinogenesis in Turcot syndrome is still unclear, we analysed genetic changes in tumors from a Turcot patient with no family history of the condition. All tumors, including one astrocytoma, three colon carcinomas, and two colon adenomas, exhibited severe replication error (RER), and all colon tumors showed somatic mutations at repeated regions of TGFbetaRII, E2F-4, hMSH3, and/or hMSH6 genes. Somatic APC mutations were detected in three of three colon carcinomas, and somatic p53 mutations were detected in the astrocytoma and two of three colon carcinomas, both of which showed two mutations without allele loss. We also found that normal colon mucosa, normal skin fibroblasts and normal brain tissue from this patient showed respective high frequencies of RER, in contrast to usual HNPCC patients in which RER was very rare in normal tissues. These results suggest that extreme DNA instability in normal tissues causes the early development of multiple cancer in Turcot syndrome. A missense mutation (GAG to AAG) at codon 705 of hPMS2 gene was detected in one allele of this patient, which was inherited from his mother without tumors. Additional unknown germline mutation may contribute to the genetic instability in normal tissues.

[Two cases of catheter tip dislocation to the duodenal bulb: a rare complication of hepatic arterial infusion chemotherapy].

Case 1: A 63-year-old woman underwent transverse colectomy and hepatectomy for colonic cancer and liver metastasis. A hepatic arterial infusion port (HAIP) was implanted. Continuous infusion of 5-FU (total amount, 7,500 mg) caused a hemorrhagic duodenal ulcer 15 months after. Follow-up endoscopy revealed the catheter tip was in the duodenal bulb. Case 2: A 62-year-old man underwent abdominoperineal resection for rectal cancer. Repeated hepatectomy for liver metastases was performed at 3 and 5 years after the first operation. HAIP was implanted at the last operation, but was not available at all due to the wound infection. The port was removed, but the catheter remained. Three years after, the catheter tip was found in the duodenal bulb by endoscopy.

[Experience of a combination chemotherapy consisting of 5-FU, MMC, and FT-207--side effects against kidney].

We are using 5-FU, MMC, and FT-207 in combination for the treatment of the patients with gastric cancer for a long term, and the renal dysfunction was found in two cases. The 1st case was a 69 years old male, suffering from gastric cancer which was unresectable. He was treated with the anticancer drugs for 2.5 years after exploratory laparotomy and no development of gastric cancer was detected endoscopically. But renal function of the patient was damaged. The 2nd case was a 58 years old male, also suffering from gastric cancer. The chemotherapy lasting for 1.5 years after gastrectomy resulted also in renal dysfunction.

[Clinical evaluation of cefoxitin for the treatment of severe gastrointestinal infections].

Some 23 patients suffering from severe gastrointestinal infections were treated with cefoxitin (CFX) at the Bokuto Metropolitan Hospital, surgical ward, from September to November, 1982. Clinical examinations were conducted and the findings bacteriologically evaluated. The following clinical results were obtained: Of 23 patients, 11 were treated for diffuse peritonitis, 5 for localized peritonitis, and 7 for cholangitis. Following treatment, 5 were judged "excellent", 12 "good", 4 "fair", and 2 "poor." The clinical efficacy rate was 74%. Antibiotic disc susceptibility testings for ampicillin, cephalexin, gentamicin, and CFX were conducted. Gram-negative rods, such as E. coli, Klebsiella sp., Proteus sp., and especially, anaerobic B. fragilis, indicated susceptibility to CFX. B. fragilis was resistant to the remaining 3 antibiotics. Transient elevations in S-GOT and S-GPT levels were observed in 2 patients. However, this was not thought to be caused by CFX. No other irregularities were found. CFX is considered to be a drug of first choice for the treatment of severe gastrointestinal infections. However, for infections due to mixed Pseudomonas aeruginosa and other bacteria, concomitant treatment with CFX and an aminoglycoside is recommended.

[Influence of schizophyllan, streptomycin and rifampicin on histopathological changes in mice infected with tubercle bacilli (author's transl)].

Experimental tuberculosis in mice infected with streptomycin-resistant Mycobacterium tuberculosis SCHACHT strain was treated with streptomycin or rifampicin alone and in combination with schizophyllan. The histopathogical tests of various organs of the treated mice were carried out. 1) In the group of mice treated with streptomycin alone, the moderate focal proliferation of RE cells were seen at the beginning of infection. However, durable activation of RE cells and the prolongation of life-span could not be recognized as compared with control animals. 2) The treatment with streptomycin-schizophyllan combination appeared to be somewhat more effective than schizophyllan alone, the phagocytic capacity being more strongly stimulated. 3) In the group treated with rifampicin alone, the therapeutic effect could be exhibited by the direct antibacterial action of rifampicin, but the activation of RE cells was slight. When rifampicin was discontinued, the growth of tubercle bacilli was rapidly resumed, and the durable therapeutic effect seemed not to be expected. Degeneration of hepatic cells tended to develop. 4) In the group treated with rifampicin-schizophyllan combination, the antibacterial effect of rifampicin appeared to be potentiated by the strong activation of RE cells by schizophyllan, showing the durable therapeutic effects.