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Biomedical subjects

K Okajima

Publications and source records attributed to K Okajima.

At least 163 records · Page 9Linked to original sources
PubMed1994

Plasma levels of granulocyte elastase-alpha 1-proteinase inhibitor complex in patients with disseminated intravascular coagulation: pathophysiologic implications.

To investigate the role of neutrophil activation in the pathophysiology and sequelae of disseminated intravascular coagulation (DIC), we measured plasma levels of granulocyte elastase-alpha 1-proteinase inhibitor complex (GEPIC) in 41 patients with DIC and 27 patients with similar underlying conditions but without DIC. Mean GEPIC levels were significantly higher in patients with DIC (421.0 +/- 45.6 ng/ml) than in patients without DIC (246.1 +/- 41.9 ng/ml, P < 0.01). Significant differences were also noted in DIC patients with or without infection (474.7 +/- 61.2 ng/ml vs. 302.4 +/- 48.9 ng/ml, P < 0.04), with or without organ dysfunction (546.6 +/- 72.7 ng/ml vs. 305.6 +/- 42 ng/ml, P < 0.01), and with or without respiratory failure (640.0 +/- 91.2 ng/ml vs. 328.1 +/- 55.1 ng/ml, P < 0.01). No significant difference was found in mean GEPIC levels in DIC patients with or without renal failure, heart failure, hepatic failure, or gastrointestinal bleeding. The frequency of respiratory failure correlated with rising plasma levels of GEPIC. Mortality was higher in patients with GEPIC levels > 500 ng/ml (53.8%) than in patients with GEPIC levels < 500 ng/ml (28.6%). This correlation was particularly strong in patients with DIC, infection, and respiratory failure. Based on these data, we suggest that neutrophil activation, triggered by the coagulation cascade and perhaps augmented by endotoxin or cytokine release with infection, significantly contributes to respiratory failure and mortality in patients with DIC.

Cardiac Output, Low↗
PubMed1994

The protective effect of thromboxane A2 synthetase inhibitor against ischemic liver injury.

To evaluate the role of thromboxane A2 (TXA2) in ischemic liver injury, the serum changes in thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) following warm ischemia of the total canine liver were examined, and the protective effect of a TXA2 synthetase inhibitor was assessed. Total liver ischemia was performed for 60 min on two groups of dogs: a control group, in which ischemia alone was performed, and an OKY-046 group, which received a TXA2 synthetase inhibitor. A temporary active portacaval shunt was used to eliminate the effects of splanchnic venous stasis during clamping of the hepatic pedicle. Postoperative changes in liver function, assessed by the transaminase enzyme levels, and in prostaglandins were recorded and the histologic liver findings of both groups 1 week after ischemia were compared. The levels of 6-K-PGF1 alpha increased after reperfusion in both groups, while those of TXB2 increased in the control group but maintained low levels in the OKY-046 group. Liver function was better and histologic changes less marked in the OKY-046 group than in the control group, suggesting the important role of TXA2 in ischemic liver injury and the usefulness of a TXA2 synthetase inhibitor for protecting the liver against ischemic injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

The significance of proliferating cell nuclear antigen (PCNA) expression in cancer of the ampulla of vater in terms of prognosis.

Seventeen patients with cancer of the ampulla of Vater were studied retrospectively using immunohistochemical staining with a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The relationships between the PCNA-positive rate, being the number of PCNA-positive cancer cells to total cancer cells, the clinicopathological findings, and the clinical course were evaluated. The PCNA-positive rate in patients with lymph node metastasis (47%) was significantly higher than that in patients without metastasis (29%), while that in patients with advanced cancer invading the pancreatic parenchyma (47%), was significantly higher than that in patients with early cancer without invasion of the sphincter of Oddi (32%). All of five patients with early cancer are still alive, whereas five with semi-advanced cancer invading the sphincter of Oddi but not the pancreatic parenchyma, and two with a PCNA-positive rate of over 40% died of recurrent cancer. Of seven patients with advanced cancer, only one with a low PCNA-positive rate of 23% is alive, but the other six with a PCNA-positive rate of over 40% all died. The results suggest that the PCNA-positive rate provides a prognostic index for cancer of the ampulla of Vater.

Ampulla of Vater↗
PubMed1994

Use of a CT simulator in radiotherapy treatment planning for breast conserving therapy.

A CT simulator (CT-S) is a real-time, CT-linked, 3-D treatment planning system, which consists of a CT scanner, a multi-image display, a treatment planning device with real-time visual optimization, and a laser beam projector. This system was clinically evaluated in 339 Stage 0, I and II breast cancers in 337 patients who received breast conserving therapy. Following quadrantectomy or wide excision with complete axillary dissection, a total of 50 Gy was delivered to the ipsilateral breast using 60Co gamma-rays. In patients with involved surgical margins, boost electron irradiation was also given. Treatment planning could be accomplished within 40-50 min using the CT-S. The parameters for the tangential portals could be optimized for each patient, and the wedge filters and the electron energy for boost irradiation could be appropriately selected. The incidence of moist desquamation and depigmentation at the areola was slightly decreased with the use of wedge filters. During the follow-up for 2-71 months (median, 22 months), local recurrence and symptomatic radiation pneumonitis occurred in one patient each. The CT-S appears to be useful for the individualized optimization of tangential irradiation fields in breast conserving therapy.

Adult↗
PubMed1994

[Overview of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer].

Reports of the results of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer were reviewed. All but two trials did not show its efficacy. In spite of this, understanding some results of subset analysis as definite proof, a consensus was achieved in Japan on its efficacy due to lack of proper knowledge of medical statistics among surgeons. Recently it has been recognized that this consensus was groundless and that evaluation of adjuvant chemotherapy should be carried out again. The results of the trial of JCOG, comparing adjuvant chemotherapy versus control (surgery alone) are therefore awaited. For the moment, all clinical trials on adjuvant chemotherapy for curatively resected gastric cancer should have an arm of surgery alone as control.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Clinical results of breast conservation therapy; a radiotherapeutical viewpoint].

Between November 1987 and March 1993, 244 breasts in 243 patients underwent breast conserving therapy at Kyoto University Hospital. Clinically, there were 159 stage I and 85 stage II tumors. Pathological staging showed 216 stage I, 24 stage II, and 4 stage III tumors. All except 10 tumors were invasive ductal carcinomas. Eleven tumors were margin--positive by histopathological examinations. As surgical treatment, quadrantectomy or wide excision with complete axillary dissection was performed. Radiation therapy consisted of 50 Gy delivered to the whole breast by opposed tangential fields over 5 weeks using 60Co gamma rays. For patients with a positive margin, boost electron irradiation was given to a total of 10 Gy. We used the CT simulator for individualized optimization of the tangential fields. Prompt and accurate determination of the tangential portals was possible by using the simulator to determine various parameters, including beam angle and the head rotation angle. During follow-up for 2-66 months (median, 20 months), unrelated death occurred in 2 patients and distant metastases developed in 5 patients (bone 4, lung 1). However, neither local recurrence nor symptomatic radiation pneumonitis has occurred. The cumulative survival rate and the disease--free survival rate at five years were 95.2% and 91.8%, respectively. These promising clinical results of breast conservation therapy encourage further clinical trials.

Breast Neoplasms↗
PubMed1994

[Clinical relevance of determination of plasma ATIII and alpha 2 PI activities in patients with DIC--application of the molecular markers for the analysis of pathophysiology of DIC].

The clinical relevance of determination of plasma antithrombin III(ATIII) and alpha 2-plasmin inhibitor (alpha 2 PI) activities in patients with disseminated intravascular coagulation (DIC) was analyzed. Although the plasma ATIII activity was decreased in patients with DIC, no significant correlation was observed between plasma level of ATIII and that of thrombin-antithrombin III complex or prothrombin fragment 1+2. The extent of the decrease of ATIII in DIC was the most marked in cases associated with septicemia. The plasma level of ATIII in septicemia without DIC was significantly lower than that in DIC cases without septicemia, suggesting that the decrease of ATIII level could not be related to the pathophysiology of DIC, but to that of septicemia. The plasma half-life of ATIII in septicemia without DIC was significantly shortened in the absence of the increase of TAT level, suggesting that the extravasation of ATIII might be induced probably due to the endothelial damage in septicemia. The alpha 2-Plasmin inhibitor level was decreased in DIC patients. The decrease was the most marked (lower than 60% of normal) in patients with excessive fibrinolysis in which fibrinogen degradation was induced. The plasma level of alpha 2PI was significantly higher in the DIC cases with septicemia than in those without septicemia. The ATIII/alpha 2PI ratio was significantly lower in DIC cases with septicemia than in those with solid tumor or acute leukemia. Moreover, the ATIII/alpha 2PI ratio was significantly lower in MOF cases than in non-MOF cases in septicemia. The mortality of the MOF cases did not correlate with the ATIII/alpha 2PI ratio, but with the plasma level of PAI-1, suggesting that the decrease of ATIII/alpha 2PI ratio might not reflect the irreversible endothelial cell damage. Based on these observations, the calculation of ATIII/alpha 2PI in DIC patients would provide the following information; (1) a low ATIII/alpha 2PI ratio (less than 0.6) was frequently observed in septicemia, which could be related to the occurrence of organ dysfunction; (2) a high ATIII/alpha 2PI ratio (higher than 1.0) with the marked decrease of alpha 2PI level (lower than 60% of normal) suggests the occurrence of excessive fibrinolysis in which anti-fibrinolytic therapy should be considered when clinical bleeding was present; (3) The ATIII/alpha 2PI ratio near 1.0 was observed in DIC associated with the pathological conditions other than described above, such as solid tumors, in which the coagulation and fibrinolysis was almost equally activated.

Adolescent↗
PubMed1994

Intraarterial infusion of autologous lymphocytes for the treatment of refractory lymphoedema. Preliminary report.

OBJECTIVE: To evaluate the results of the treatment of lymphoedema by intra-arterial infusion of autologous lymphocytes. DESIGN: Open study. SETTING: University Hospital. SUBJECTS: 13 patients with refractory lymphoedema. INTERVENTIONS: Lymphocytes were separated from the patient's own blood using a blood cell separator; about 100 cc of lymphocyte dominant blood separated from this blood was immediately infused into the proximal artery of the affected limb. Infusion was practiced once a week, and repeated 4 to 6 times. MAIN OUTCOME MEASURES: Change in size of the affected limb (defined as the difference between the affected limb and the normal limb after treatment), and softening of the edema (measured with a tension gauge). RESULTS: In all 13 patients there was softening of the affected hard limb followed by a reduction in the size of the limb (mean 64%), and the ache and sensation of heat in the limb lessened. The reduction in size was maintained in 9 of the 13 patients for three months, despite returning to their normal activities. CONCLUSION: Intra-arterial infusion of autologous lymphocytes is a promising treatment for refractory lymphoedema.

Adolescent↗
PubMed1994

Granulocyte proteases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro.

Leukocytes release lysosomal proteases and reactive oxygen species in response to various stimuli that damage the adjacent endothelial cells. We investigated the effects of granulocyte lysosomal proteases (granulocyte elastase [GE] and cathepsin G [CG] and/or hydrogen peroxide (H2O2) on thrombomodulin (TM) activity of endothelial cells. We wished to determine whether the activated leukocytes damage the nonthrombogenic systems of endothelial cells. When cultured human umbilical vein endothelial cells (HUVECs) were incubated with GE, TM activity of the cells (as judged by the protein C activation capacity) decreased to about 10% of control with the concomitant increase of immunoreactive TM concentration in the conditioned media. CG also decreased TM activity to about 20% of control with the concomitant increase in immunoreactive TM concentration in the conditioned media. The GE- or CG-induced inactivation of TM was not observed in the presence of alpha 1-proteinase inhibitor. Immunoblot analysis showed that CG cleaved purified TM to yield one major fragment with an M(r) of 43,000; TM activity of this fragment was about 10% of the control activity. When purified TM was incubated with GE, TM activity decreased to 10% of control, and no detectable band was found on immunoblotting, suggesting that CG and GE cleave TM into inactive fragments and that GE degrades the epitope structure of TM. Although H2O2 (1.0 mmol/L) enhanced chromium 51 release from prelabeled HUVECs after 30 minutes of incubation, it decreased TM activity only slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Cathepsin G↗
PubMed1993

Antithrombin III Nagasaki (Ser116-Pro): a heterozygous variant with defective heparin binding associated with thrombosis.

A novel variant of antithrombin III (AT III) that lacks affinity for heparin was found in a 33-year-old man who suffered from recurrent cerebral infarction. The propositus had a history of recurrent ischemic attacks from the age of 28. He was obese and had a smoking habit (30 to 40 cigarettes/day), low high-density lipoprotein cholesterol, and a mild glucose intolerance as the possible risk factors for thrombosis. No family history of thromboembolic episodes was observed. Coagulation studies found low heparin cofactor activity (55%) of AT III, with a normal immunoreactive level (109.7%) and progressive antithrombin activity (117%). Other factors capable of predisposing him to hereditary thrombophilia were within normal ranges. Analysis by crossed immunoelectrophoresis in the presence of heparin and affinity chromatography on heparin-Sepharose demonstrated that the propositus' AT III was composed of two populations, one having no affinity for heparin and the other binding heparin normally. Nucleotide sequencing of 7 exons of the propositus' AT III gene using polymerase chain reaction and subcloning disclosed a transition of thymine to cytosine in exon 3a (codon 116) of the AT III gene leading to a Ser116-Pro conversion. Allele-specific oligonucleotide hybridization procedures confirmed the presence of the mutation in the propositus' genomic DNA. Using the same technique, the mutation was also found in his father's genomic DNA, but not in that of his mother. These findings indicate that Ser116 is an important amino acid residue in heparin binding and that the propositus is heterozygous for the abnormality. Furthermore, the fact that the propositus suffered from recurrent cerebral infarction suggested that being heterozygous for a heparin-binding defect would lead to a predisposition to thrombosis when associated with various risk factors. The name AT III Nagasaki is proposed for this variant AT III containing a novel Ser116-Pro mutation.

Adult↗
PubMed1993

Prognostic value of the number of metastatic lymph nodes in gastric cancer with radical surgery.

To evaluate the effectiveness of extended lymph node dissection in gastric cancer, the relationship between the number of lymph nodes with metastasis and the long-term outcome was studied retrospectively in 761 patients who underwent curative resection with extensive lymph node dissection. The cumulative 5-year survival rate was 85.8% in patients without lymph node metastasis, 60.2% in those with 1-4 lymph nodes, 35.6% with 5-10 nodes, and 12.3% with 11 or more nodes involved. Concerning N2 or N3 patients in whom metastatic lymph nodes would have remained without extensive dissection, the 5-year survival rate was 70.5% in those with 1-4 lymph nodes involved and 44.0% with 5 or more lymph nodes involved when no serosal invasion was observed. It was 38.5% with 1-4 lymph nodes and 5% with 5 or more lymph nodes involved when serosal invasion was observed. These results suggest that extensive lymph node dissection is effective in gastric cancer patients without serosal invasion and, when only a few lymph nodes are involved, also in those with serosal invasion. However, it is not considered to be effective in patients with serosal invasion and metastasis to many lymph nodes. Combination therapies are thought to be required in such patients.

Adult↗
PubMed1993

The successful surgical management of perforation after endoscopic sphincterotomy: report of two cases.

Retroperitoneal perforation following endoscopic sphincterotomy (EST) is an infrequent but serious complication with a high mortality rate in patients who do not receive prompt treatment. We report herein two cases of perforation, diagnosed 3 and 7 days after EST, one of whom was treated by choledochojejunostomy (Roux-en-Y) and suturing of the perforation site with jejunal patching, and the other by pancreatoduodenectomy. Both operations were successful as emergency treatments and therefore we consider that radical surgery should be attempted for cases of perforation after endoscopic sphincterotomy with a delayed diagnosis.

Aged↗
PubMed1993

Surgery for cholelithiasis in cirrhotic patients.

Although biliary tract surgery for cholelithiasis is performed frequently in Japan, cirrhotic patients require special consideration. Postoperative complications after biliary tract surgery were studied in 23 patients with liver cirrhosis and associated cholelithiasis, 9 of whom had no complications, 8 had minor complications, and 6 had severe complications. Concerning the relation between Child's classification and postoperative complications, no complications were seen in four Child's type A patients, but seven of ten (70%) Child's type B patients and seven of nine (78%) Child's type C patients developed complications. Two (20%) of the Child's type B patients and four (44%) of the Child's type C were severe, and three of the latter group died. Regarding the preoperative laboratory findings, significant differences were seen between the patients without complications and those with severe complications in serum bilirubin, albumin, and ICG R15 values. Of the six patients with severe complications, five had choledocholithiasis, three of whom died of liver failure, while two developed biliary peritonitis caused by insufficient fistula formation after removal of the T-tube. Thus, for the treatment of choledocholithiasis in patients with severe cirrhosis, avoiding surgical invasion through the use of such techniques as endoscopic papillotomy is recommended whenever possible.

Biliary Tract Surgical Procedures↗
PubMed1993

Endoscopic evaluation of the depth of invasion of the depressed type early gastric cancer and apparently early advanced cancer in cases of a peptic ulcer within the cancer lesion.

Depressed-type early and apparently early advanced cancers were divided into two groups according to whether or not an associated peptic ulcer was present within the cancer lesion, and the accuracy of preoperative endoscopic diagnosis was reviewed. As a result it was found that evaluation of depth of invasion was more difficult in the ulcer [UL(+)] group than in the group without an ulcer [UL(-)]. In the UL(+) group it was difficult to identify endoscopic findings which indicate depth of invasion at the tip of the folds, the volume of cancer invasion of the deeper layers was small, and there many cases of invasion of deeper layers in a portion of the margins of the peptic ulcers.

Adenocarcinoma↗
PubMed1992

Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer.

Although the possible occurrence of systemic fibrinogenolysis has been suggested in patients with metastasising prostatic cancer (MPC), direct evidence is lacking. We report on a patient with MPC whose laboratory data were consistent with hyperfibrinolysis: marked decrease of alpha 2-antiplasmin (AP) level (less than 50% of normal), increase of plasmin-alpha 2-antiplasmin complex, D-fragment of fibrin and fibrinogen degradation products [FDP(D)] and cross-linked fibrin degradation products (XDP). The patient neither showed laboratory nor clinical evidence for consumption coagulopathy except for a slight increase in thrombin-antithrombin III complex level. Immunoblotting of the patient's serum using an anti-fibrinogen antibody revealed the presence of a 250 kDa protein in addition to DD fragments. Following reduction of this protein by 2-mercaptoethanol after extraction from SDS-PAGE gel, gamma-chain of fibrinogen (47 kDa) was found by immunoblotting using a monoclonal antibody recognising a 86-302 residue of the gamma-remnant of fibrinogen. Moreover, the 250 kDa protein did not bind to Sepharose 4B to which a monoclonal antibody recognising the N-terminus of fragment D was conjugated. These findings indicated that this protein was not fragment DY, but rather fibrinogen fragment X. With the retraction of the prostatic tumour by an effective therapy, the patient's AP level increased gradually. When the plasma AP level rose to 60% of normal, the fragment X was no longer detectable. These findings suggested that systemic fibrinogenolysis occurred in the patient with MPC only when AP levels were markedly decreased.

Aged↗