Arterial switch operation for simple transposition of the great arteries in infancy

Five infants (22-42 days of life) underwent arterial switch operation for simple transposition of the great arteries under deep hypothermic cardio-pulmonary bypass. Three babies required prostaglandin E1 infusion to keep ductus arteriosus opened widely before surgery. Balloon atrioseptostomy was necessary in 0-10 days of life in all babies because of poor condition. Left to right ventricular peak pressure ratio ranged from 0.75 to 0.86, preoperatively. Four of the five survived the operation, and one died of coronary insufficiency because of kinking of the implanted coronary artery. Hypothermic circulatory arrest was used in three (38-41 minutes). Aortic cross clamp time was 70-100 minutes, and cold crystalloid cardioplegia was given only one time just after aortic clamp in 3 babies. Single dose of cardioplegia protected left ventricular muscle well in babies with transposition of the great arteries as same as multiple dose method used in those with ventricular septal defect.     

Essential thrombocythemia transformed to acute myeloblastic leukemia

A 48-year-old woman was referred to Tohoku University Hospital in November 1981 because of leukocytosis pointed out in a group examination. At that time white blood cell count was 26.8 x 10(3)/microliters with no blasts, platelet count 268.0 x 10(4)/microliters and hemoglobin 11.4 g/dl. Bone marrow aspirates showed marked increase of megakaryocytes (15,900/microliters). Bone marrow chromosome analysis revealed 46, XX, -18, +mar without Ph1 chromosome, and DNA analysis showed no bcr rearrangement. She was diagnosed as having essential thrombocythemia and was treated with busulfan. On November 1986, she developed remarkable leukocytosis with leukemic blasts. White blood cells reached 153 x 10(3)/microliters with 33% blasts. Her blasts were positive for peroxidase staining, but negative for platelet peroxidase on electron microscopic study and platelet specific glycoproteins. A diagnosis of acute myeloblastic leukemia (M2) was made. The patient received various combination chemotherapy, which was ineffective, and she died due to pneumonia on June, 1989. In Japan, there has been reported only 8 cases of essential thrombocythemia transformed to acute leukemia. The clinical pictures of these 9 cases were discussed.     

Characterization of polyethylene glycol-modified L-asparaginase from Escherichia coli and its application to therapy of leukemia

For the purpose of clinical application to the therapy of human leukemia and lymphosarcoma, L-asparaginase from Escherichia coli was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2) by an improved method, which involves a purification step of activated PEG2 by gel filtration. The PEG2-modified asparaginase retained approximately 30% (73 IU/mg of protein) of the enzymic activity of the native enzyme, while it had almost wholly lost the immunoreactivity towards anti-asparaginase antibodies. The modified enzyme retained the characteristics of the native enzyme in terms of the pH- and temperature-dependencies of activity and stability, and the Km value for L-asparagine. Administration of the modified enzyme to a dog with spontaneous lymphosarcoma induced complete remission without any toxic side effects. Seven children with multiple relapses of acute leukemia were treated with a regimen of cycles of methotrexate and native asparaginase. Three of these children developed anaphylactic shock. In contrast to the native enzyme, the successive administration of PEG2-modified asparaginase to those three patients was therapeutically effective without causing any allergic reaction.     

A bioassay of cisplatin by human tumor clonogenic assay

A new bioassay method for cis-diamminedichloroplatinum (CDDP) using a human tumor clonogenic assay (HTCA) was developed and used to examine the pharmacokinetics of the active form of CDDP in different schedules of administration. The inhibition of colony growth of tumor cells decreased with increase in the % of fetal calf serum in RPMI1640 containing CDDP. By means of this assay, four administration schedules (A, B, C and D) of CDDP were examined. In patients given 40 mg/m2 of CDDP by iv infusion on day 1 twice with a 1 hr interval (schedule A), total platinum was still detectable in plasma at 6 hr by atomic absorption assay. However, the active form of CDDP was no longer detectable at 30 min. In patients treated with 20 mg/m2 of CDDP iv for 20 min daily (schedule B) from day 1 to day 4, the level of total platinum showed a cumulative increase. However, the active form of CDDP was no longer detectable at 30 min, and no cumulative effect was observed. In patients given a high dose (120 mg/m2) of CDDP iv for 30 min on day 1 (schedule C), the peak concentration of active form of CDDP was determined to be 5.0 to 7.0 micrograms/ml, and a level of more than 1.0 micrograms/ml was maintained even after 2 hr in one case. In 2 patients of this group the concentrations of active form of CDDP determined by HTCA were the same as those of ultrafiltrable platinum detected by atomic absorption assay. In 2 of 3 patients given 100 mg of CDDP into the pleural cavity, the active form of CDDP was detected in sera. High-dose CDDP administration was concluded to be preferable to low-dose therapy because of the higher peak concentration and longer residence time of the active form of CDDP in the plasma. Furthermore, it is suggested that a systemic effect of CDDP can be expected even when CDDP is given by intrapleural administration.     

An epidemiological study of the influence of sweets intake and toothbrushing on dental caries among children in Japan

The study was designed to determine the influence of confectionery and beverages intake and of toothbrushing on infant dental caries. The participants were 700 three year old Japanese children from an urban area near Tokyo. The prevalence of caries in those who frequently consumed confectionery and beverages was higher than the prevalence in those who did not take them. However, the prevalence in children with a habit of toothbrushing did not differ from that of those without the habit. This study shows that restricting consumption of confectionery and beverages may be effective in preventing dental caries; however, encouragement of toothbrushing may not be effective in limiting dental caries progression.     

Effect of conivaptan, a combined vasopressin V(1a) and V(2) receptor antagonist, on vasopressin-induced cardiac and haemodynamic changes in anaesthetised dogs.

The neurohormonal factor arginine vasopressin (AVP) produces potent systemic vasoconstriction as well as water retention in the kidneys via the V(1a) and V(2) receptors, respectively. Therefore, AVP may be considered as an aggravating factor of cardiac failure. In the present study, the effects of intravenous (i.v.) infusion of AVP on cardiovascular parameters and the effect of conivaptan (YM087, 4'-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride), a vasopressin V(1a)/V(2) receptor antagonist, on AVP-induced cardiac and haemodynamic changes were investigated in pentobarbitone-anaesthetised dogs. The i.v. infusion of AVP (0.12-4mUkg(-1)min(-1)) dose-dependently produced decreases in the cardiac contractility indicator LV dP/dt(max) and cardiac output (CO) and increases in left ventricular end-diastolic pressure (LVEDP) and total peripheral resistance (TPR). These changes accurately mimic the cardiovascular symptoms of congestive heart failure. The i.v. bolus injection of conivaptan (0.1mgkg(-1)) rapidly attenuated the AVP (4mUkg(-1)min(-1))-induced decrease in CO and reversed the AVP-induced elevation in both LVEDP and TPR. In conclusion, i.v. infusion of AVP produced cardiac dysfunction and vasoconstriction in pentobarbitone-anaesthetised dogs. Conivaptan demonstrated the ability to dramatically improve the impaired cardiovascular parameters induced by AVP. The results suggest the potential usefulness of conivaptan in treating congestive heart failure.     

Detection of amplified DNA sequences in gastric cancers by a DNA renaturation method in gel

A DNA renaturation method in gel was used to detect amplified DNA fragments in eight gastric cancer cell lines, KATO-III, OKAJIMA, SCH, MKN1, MKN7, MKN28, MKN45 and MKN74 cells, and tissues of three metastases of gastric cancers to lymph nodes. There were amplified DNA sequences in three gastric cancer cell lines. Judging from the intensities of the bands, HindIII-digested DNA fragments were amplified several hundred times in the KATO-III and MKN7 cell lines. DNA from OKAJIMA cell line contained multiple bands with less intensity. KATO-III cells were found to contain a homogeneously staining region in chromosome 11.     

Histological findings determining disease-free survival rate

Histological findings of malignant tumors were reviewed in relation to the prognosis following surgery, radiotherapy and/or chemotherapy. To say the histological grading of malignancy by differentiation (maturation), estimation of it seemed to be subjective and it did not always correlate with the disease free survival rate. Histological findings which indicated a high degree of tumor-host interaction were a good predictor of the prognosis as well as the cell type, and the disease free survival rate of the cases with these findings was relatively higher following not only surgery, radiotherapy but also chemotherapy.