Correlation between angiographic features and pathologic changes in breast carcinoma.

The correlation between angiographic tumor blushing and underlying pathologic factors was studied. Twenty female patients with breast cancer were divided into three groups according to the degree of tumor blushing. Primary tumors were divided into three areas: marginal, central and intermediate areas. In each area, the number of blood vessels per 10(4) mu 2 was randomly counted in 10 fields and a mean value of vessels was compared among the three groups. It was found that the following pathologic findings were significantly related to strong angiographic staining: (i) well-circumscribed border; (ii) large tumor nest; (iii) severe inflammatory cell infiltration; (iv) mild stromal fibrosis; and (v) absence of lymph node metastasis. The mean value of blood vessels in the strongly positive group was significantly increased in the overall and the intermediate areas. The density of the vessels in the intermediate area was thus thought to be responsible for the tumor blushing.

Six-base deletion occurring in messages of human cytochrome P-450 in the CYP2C subfamily results in reduction of tolbutamide hydroxylase activity.

We isolated and expressed a clone, hPA6, possibly corresponding to the CYP2C9 cDNA. Compared with the other CYP2C9 cDNA clones, hPA6 showed a 6-nucleotide deletion near its middle. From the same cDNA library, we could also isolate another cDNA clone, named hPA22, which retained the 6 bases. For clarification of the effect of the 2-amino acid deletion resulting from the 6-base deletion on enzymatic activities, both clones were expressed in yeast. The expressed enzymes showed tolbutamide hydroxylase activities, and these activities were inhibited by antibodies against P-450-HM2, a probable CYP2C9. The activity of the enzyme encoded by hPA6 was lower than that encoded by hPA22; thus the 2-amino acid deletion in the CYP2C9 reduced the enzymatic activity.

[A case report of atypical coarctation of the aorta with coarctation and left subclavian arterial aplasia].

A 18 year-old female was admitted to our hospital with hypertension of 190/100 mmHg in her right arm and 140/110 mmHg in the left arm. Femoral arterial pulsation was not palpable. Her physical status and growth of the lower limbs were normal. Aortography demonstrated slight coarctation with a pressure gradient of 10 mmHg and descending aortic stenosis with a pressure gradient of 80 mmHg. Main three branches from aortic arch were anatomically normal. However, the left subclavian artery distal to the origin of the left vertebral artery was not visualized and the axillary artery was perfused by collaterals. Atypical coarctation was replaced using a woven Dacron graft of 14 x 40 mm. Postoperatively proximal pressure decreased from 180/113 to 156/98 mmHg and there was no pressure gradient between proximal and distal of the graft. After six months blood pressure in the right arm gradually decreased to 120/78 mmHg.

Fetus-specific expression of a form of cytochrome P-450 in human livers.

The developmentally regulated expression of forms of cytochrome P-450, namely, those encoded by lambda HFL33 and NF25 or HLp cDNAs, which were isolated from respective fetal and adult human liver cDNA libraries, was investigated. When EcoRI fragments of cDNA clones of lambda HFL33 and NF25 were used as probes, these probes hybridized with RNA from both fetal and adult human livers. However, when oligonucleotides specific to the coding and 3'-noncoding region of lambda HFL33 (oli-HFL and oli-HFL3', respectively) were used as probes, these probes gave hybridizable bands with RNA from fetal but not adult livers. On the other hand, an oligonucleotide probe specific to the coding region of NF25 and HLp (oli-NF) gave positive bands with RNA only from adult livers. These results indicate that P-450(HFL33) is expressed specifically in fetal livers and that neither P-450NF nor HLp is expressed in fetal livers, but one or both are expressed in adult livers.

[A radical operation of Chiari's disease using the internal shunt tube of the inferior vena cava].

A case with the Budd-Chiari syndrome due to the right hepatic occlusion who was successfully operated by using the internal shunt tube of the inferior vena cava was reported. The patients was 33 year old male. Midsternal incision and right subcostal oblique incision were made and the internal shunt tube was inserted through the right auricle to the inferior vena cava. The hepatic vein was approached through the longitudinal suprahepatic caval venotomy. Then membranous obstruction in the right hepatic vein ostia was resected. Mesenteric venous pressure dropped immediately from 360mm H2O to 160mm H2O by direct manometry. All the blood bled from the right hepatic vein was transfused through the internal shunt tube to the right atrium. The patient tolerated the procedure and his postoperative course was free from the complication. The resected membrane was congenital anomaly and an operative liver biopsy was demonstrated the evidence of congestive liver with fibrosis.

Ceftazidime concentration in gallbladder tissue and excretion in bile.

Ceftazidime was given to 16 patients with cholelithiasis, and its concentrations in bile and the gallbladder wall were studied. The results suggest that ceftazidime is effective against biliary tract infection.

[Antibiotic susceptibility of bacteria isolated from surgical infection (second report)].

Isolated bacteria from infections in general surgery in 1984 and 1985 have been investigated to find bacterial composition and their susceptibilities to antibiotics in a joint research in which 6 university hospitals in Japan participated. A summary of findings from the investigation is as follows. 1. One hundred and seventy-two (1984) and 211 (1985) cases were included in the study. Cases in which bacteria were detected were 147 and 174 in the respective years. The detection rate was higher than 80% in either year. 2. Total numbers of strains isolated in 1984 and 1985 were 267 and 293, respectively; major sources of these strains were intraperitoneal infection exudates in either year. 3. The most frequent isolate from primary infection cases in both years was Escherichia coli (15-21%), followed by Bacteroides spp. and Staphylococcus spp., in that order. The most frequently isolated from postoperative infection cases were Enterococcus spp. (16-22%), followed by Pseudomonas spp. The diversity of isolated species, as well as the similarity of incidences of different species were noted in cases of postoperative infections. It is suspected that a certain species, even if its pathogenicity is essentially low, may become to be a causative organism once its number increases due to its survival through a perioperative prophylactic use of antibiotics, and also due to the decreased host resistance to infections caused by underlying diseases or surgical stress. 4. Staphylococcus spp. was the most frequent isolate from postoperative infections occurring after clean operations, while Enterococcus spp. and Pseudomonas aeruginosa were major isolates from infections after clean-contaminated operations. Isolates from infections occurring after contaminated operations included Enterococcus spp. greater than E. coli greater than Klebsiella pneumoniae, P. aeruginosa, Bacteroides spp. (1985). 5. In cases without the presence of clinical factors cause by depressed host defense, E. coli and Bacteroides spp. were major isolates, while in cases with the factors, a wide variety of bacterial population tended to be found. 6. Before an administration of antibiotics in primary infections, E. coli, Staphylococcus spp. Bacteroides spp. and Klebsiella spp. were most commonly isolated, while after a chemotherapy, Enterococcus spp. were the most frequent isolates, followed by P. aeruginosa during 1985. These findings reflected the antibacterial spectrum of cephems usually used in surgical field.(ABSTRACT TRUNCATED AT 400 WORDS)

[A surgical case of aneurysm of the persistent sciatic artery].

Seventy two-year-old woman was admitted in September, 1985 to our hospital with complaints of painful mass in the right buttock and ischias. Aorto-peripheral arteriogram showed that enlarged right internal iliac and inferior gluteal arteries passed posteriorly to cross the right hip and down the posterior aspect of the femur to supply the popliteal artery. A saccular aneurysm was seen immediately posterior to the right femoral head. The femoral artery was small in size, but connecting to the popliteal artery. Delayed flow to the popliteal artery through the sciatic artery was noted in contrast to the femoral system. With Osborne's right buttock approach, the gluteus maximus muscle was divided in the direction of its fibers, exposing a 3.5 by 5 cm aneurysm which was located above, the sciatic nerve and adherent to it. The proximal sciatic artery and the trunk of the sciatic nerve passed beneath the piriformis muscle. The pressure of the dorsalis pedis artery decreased from 156/77 to 117/72 mmHg after ligation of the proximal sciatic artery. The aneurysm was dissected free from the sciatic nerve. Postoperatively she had no more gluteal discomfort, nor did she have any ischemic symptoms by walking.

[Clinical studies of BRL 28500 (clavulanic acid/ticarcillin) in the treatment of intraperitoneal infections and biliary tract infections].

Clinical studies have been conducted on BRL 28500 (a formulation containing 15 parts ticarcillin (TIPC) plus 1 part clavulanic acid (CVA]. BRL 28500 was administered at doses of 1.6 g or 3.2 g b.i.d., generally for 10 days by drip infusion to patients with intraperitoneal infections or biliary tract infections. Drug concentrations in the ascites were determined. A total of 76 cases was treated with BRL 28500. These cases included 49 intraperitoneal infections (suppurative peritonitis 29, postoperative peritonitis 20) and 18 biliary tract infections (cholecystitis 5, cholangitis 13). Nine cases were excluded from evaluation according to the committee's assessment. The clinical improvement as assessed by surgeons in charge increased with the duration of continued treatment and efficacies were assessed as 57.1% on day 5, 63.1% on day 7 and 77.8% on day 10 in intraperitoneal infections. Corresponding results in biliary tract infections were 38.9%, 40.0% and 42.9%, respectively. From these results, it is clear that the degree of improvement is related to the duration of treatment. The clinical usefulness as assessed by surgeons in charge of the study was 63.8% in intraperitoneal infections (suppurative peritonitis 75.0%, postoperative peritonitis 47.4%) and 58.8% in biliary tract infections (cholecystitis 100%, cholangitis 41.7%). The overall rate of usefulness was 62.5%. The clinical efficacy rates as assessed by the committee were 81.6% in intraperitoneal infections (suppurative peritonitis 93.1%, postoperative peritonitis 65.0%) and 66.7% in biliary tract infections (cholecystitis 100%, cholangitis 53.8%). In cases where causative organisms were isolated, the efficacies were 92.9% in suppurative peritonitis, 58.8% in postoperative peritonitis, 50.0% in cholangitis and overall, 69.2%. In cases from which TIPC-resistant organisms were isolated, the overall efficacy rate was 65.4% (suppurative peritonitis 88.9%, postoperative peritonitis 58.3% and cholangitis 40.0%). Regarding bacteriological effect as assessed by the committee, the eradication rate was 76.9% in intraperitoneal infections and 40.0% in biliary tract infections (71.0% overall). In cases from whom ticarcillin-resistant organisms were isolated the corresponding rates were 68.4% and 33.3% respectively, (63.6% overall). In 4 patients with peritonitis drug levels in the ascites were determined following administration of BRL 28500 by drip infusion. Good levels of both TIPC and CVA were detected 1 to 3.5 hours after administration.(ABSTRACT TRUNCATED AT 400 WORDS)

[Antibiotic susceptibility of bacteria isolated from surgical infections (first report)].

In vitro activities of several antimicrobial agents against bacterial pathogens isolated from patients with primary and postoperative infections were investigated in 1982 and 1983. Antimicrobial agents examined were as follows: sulbenicillin (SBPC), piperacillin (PIPC), cephalothin (CET), cefazolin (CEZ), cefmetazole (CMZ), cefotiam (CTM), cefoperazone (CPZ), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), lincomycin (LCM), gentamicin (GM) and amikacin (AMK). Specimens for bacterial isolation included plus, fluid drawn by centesis, or bile. Blood samples of septicemia were excluded. The antimicrobial activities of these drugs were determined by the agar plate dilution method of the Japanese Society of Chemotherapy. There were 123 strains obtained in the 1982 survey and 252 strains in the 1983 survey. Little or no differences were seen in frequencies of isolation between the isolates of principal species in 1982 and those in 1983. Isolation frequencies of pathogens in primary infections were, in an order of decreasing frequency, E. coli (25.6%), anaerobes (21.1%), Streptococcus sp. (14.3%), Staphylococcus sp. (11.3%); in postoperative infections, Streptococcus sp. was most frequent (28.6%), followed by Pseudomonas sp. (17.6%), anaerobes (12.6%), E. coli (10.9%), Staphylococcus (10.1%). Against S. aureus, CEZ, CTM, LCM and GM had similar degree of activity with CET being somewhat more active. CMX was the most active drug among the third generation cephems tested against S. aureus. No strain was CTM, CEZ, and LCM-resistant at the same time. Over 90% of E. coli, were sensitive to CTX, CZX and CMX, inhibited by 0.10 microgram/ml, while E. coli were slightly less susceptible to CPZ and LMOX. Penicillins were not very active against K. pneumoniae, and only 60% of K. pneumoniae were inhibited by PIPC at concentrations of 12.5 micrograms/ml. Third generation cephems, CTX, CMX and CZX, proved highly active against K. pneumoniae; over 90% of K. pneumoniae was inhibited by CTX, CMX and CZX at a concentration of 0.10 microgram/ml. About 60% of P. aeruginosa was inhibited by 3.13 micrograms/ml of PIPC and GM but was resistant to SBPC. This survey should be very useful for the selection of an appropriate drug for prophylaxis if the frequencies of incidences of pathogens in postoperative infections are taken into account in selecting the most active antibiotic agent(s) against the most frequent genus, genera and species of pathogens.

Effects of basement membrane matrix on the culture of fetal mouse hepatocytes.

The effects of laminin, fibronectin and type IV collagen, all of which are major matrix components of the basement membrane, upon fetal mouse hepatocyte culture were studied. Among these matrices, laminin showed the greatest effect on DNA synthesis, cell proliferation, the secretion of alpha-fetoprotein and cell attachment. The effects of fibronectin and type IV collagen were slight with regard to the promotion of growth and cell attachment. However, there were no differences in the secretion of albumin into the media among the groups. These results suggest that laminin may be necessary for the cellular growth and functional maintenance of immature liver cells during normal development of the liver in vivo.

Modulation of fetal mouse liver cells cultured on a pigskin substrate.

Mouse fetal liver cells cultured on a pigskin epidermal substrate grew for 7 weeks. Different enzymes and proteins, i.e. gamma-glutamyl transferase (GGT), nonspecific esterase (NE), lactic dehydrogenase (LDH), alpha-fetoprotein (AFP), and albumin were studied histochemically and/or biochemically. The activity of GGT was high at the beginning of culture and then decreased rapidly. The activities of NE and LDH were high during the culture. Release into the media and localization of AFP suggested active synthesis during the early stages. AFP levels gradually decreased and could be demonstrated only in trace amounts after 3-4 weeks of culture. On the other hand, the production of albumin was weakly evident early and became more and more evident after the second week in culture. Hydrocortisone modulated AFP and albumin production. The effect of hydrocortisone was to prolong expression of AFP and to reduce expression of albumin. Electron microscopic observations showed that the cultures consisted of organelle-rich parenchymal cells associated with the pigskin basement membrane by pseudopod-like structures. These results indicate that fetal mouse parenchymal cells were cultured and modulated on a pigskin epidermal substrate.

[Study on the serum concentrations of gentamicin after intravenous drip infusion].

Serum concentrations of gentamicin (GM) were monitored after intravenous drip infusion of 60 mg over 30 minutes, 1 hour and 2 hours. These concentrations were compared with those after intramuscular injection. The mean peak serum concentration obtained at 30 minutes after intramuscular injection (5.09 micrograms/ml) and those obtained at the end of intravenous drip infusion (5.17--6.66 micrograms/ml) were comparable. Serum concentrations decreased to less than 2.0 micrograms/ml at 6 to 8 hours after injection or infusion in all cases except 1 with less body weight than others. Pharmacokinetic analysis showed that the T1/2 of GM ranged from 2.49 to 4.33 hours and that the AUC ranged from 19.66 to 27.09 hr X micrograms/ml. Results obtained in this study suggested that the usefulness of intravenous drip infusion over the time from 30 minutes to 2 hours is equal to that of intramuscular injection in the GM therapy.

Effects of laminin, fibronectin and type IV collagen on liver cell cultures.

The effects on mouse liver cells of laminin, fibronectin and type IV collagen, all of which are the main matrix of the basement membrane, were studied. Laminin, a glycoprotein isolated from cultures of rat yolk sac carcinoma cells, promoted the attachment of mouse fetal liver cells to laminin-coated dishes, but did not have a strong influence upon the attachment of normal adult liver cells. On the other hand, fibronectin which was purified from mouse plasma promoted the attachment of adult liver cells but not that of fetal liver cells. The number of neonatal liver cells attached to the surfaces coated was intermediate between those of fetal and adult liver cells in each matrix. DNA synthesis and cell proliferation during the culture of full-term fetal liver cells in laminin-coated dishes were higher than those in fibronectin- or type IV collagen-coated dishes. The amount of alpha-fetoprotein secreted in the laminin-coated dishes was more than in other groups. No differences in secretion of albumin into media, however, were observed in either group. These results suggest that laminin may be necessary for cell growth, tissue organization and cell differentiation during the normal development of liver in vivo.

The TM bubble oxygenator: development and clinical application.

A bubble oxygenator (the TM or the OCVC oxygenator) has been produced with development efforts focused particularly on reduction of the nonphysiological characteristics of this type of oxygenator. The structural features of the apparatus are: (1) a reduction to the minimum of adequate priming volume, (2) an oxygen disperser designed to ensure evenly dispersed, uniform-sized bubbles, (3) a volume-control system for the oxygenating chamber (the OCVC system) based on extensive experimental oxygenation studies, and (4) an integrated double microfilter of the gravity-drainage type. Clinical features are: (1) ease of operation in perfusion, (2) reduction in hemolysis and postoperative blood loss, and (3) fewer complications associated with microemboli. Clinical use on over 200 infants and children proved generally very satisfactory. The background of its development is briefly described as are future modification plans.