Electromagnetic fields inhibit endothelin-1 production stimulated by thrombin in endothelial cells.

Electromagnetic field (EMF) radiation has been found to induce arteriolar dilatation, but the mechanism of action remains largely unknown. This study investigated the effect of EMF radiation on the production of endothelin-1 (ET-1), a potent vasoconstrictor, by cultured endothelial cells. EMF radiation reduced ET-1 basal levels in human umbilical vein and microvascular endothelial cells, but failed to reduce ET-1 basal levels in bovine and human aortic endothelial cells. EMF radiation significantly inhibited thrombin-stimulated ET-1 production in all four endothelial cell types in a dose-dependent manner. EMF radiation significantly inhibited thrombin-induced endothelin-1 mRNA expression in all four cell types. The inhibitory effect of EMF radiation on ET-1 production was abolished by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (10(-3) mol/1). These results demonstrate that EMF radiation modulates ET-1 production in cultured vascular endothelial cells and the inhibitory effect of EMF radiation is, at least partly, mediated through a nitric oxide-related pathway.

Inhibitory effect of a synthetic protease inhibitor (gabexate mesilate) on the respiratory burst oxidase in human neutrophils.

We investigated the mechanism by which the synthetic protease inhibitor gabexate mesilate inhibits the production of the superoxide anion by human neutrophils. We found that gabexate mesilate suppressed SOD-inhibitable cytochrome c reduction in a dose-dependent manner in intact neutrophils activated with phorbol ester. Gabexate mesilate slightly scavenged the superoxide anion in the pyrogallol assay. The reagent also inhibited superoxide anion production in a dose-dependent manner in a cell-free oxidase-activating system. Translocation of the cytosolic respiratory burst oxidase components, the 47- and 65-kDa proteins, to membranes was suppressed by the reagent in intact cells stimulated with phorbol ester. Gabexate mesilate also reduced arachidonic acid-induced translocation of the components to the membrane fraction in the cell-free system. These results demonstrate that gabexate mesilate suppresses superoxide anion production by reducing the translocation of the 47- and 65-kDa proteins to the plasma membrane.

Influence of coexisting cirrhosis on long-term prognosis after surgery in patients with hepatocellular carcinoma.

BACKGROUND: As one of the reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC) and cirrhosis, the influence of cirrhosis itself has not been clarified. METHODS: We compared the postoperative long-term courses of patients with HCC and cirrhosis with the courses of patients with HCC and without cirrhosis to determine how the coexisting cirrhosis affected the prognosis after surgery. The patients with HCC who underwent curative hepatic resection consisted of 142 with associated histologically confirmed cirrhosis and 48 without cirrhosis. RESULTS: The 5-, 7-, and 9-year survival rates were 44%, 32%, and 26%, respectively, in the patients with cirrhosis and 68%, 57%, and 57%, respectively, in the patients without cirrhosis. The prognosis of the group with cirrhosis was significantly worse than that of the group without cirrhosis. The main cause of death in both groups was cancer recurrence. The patients with cirrhosis had significantly lower recurrence-free survival rates at 3 years and later than had the patients without cirrhosis. A comparison of the background factors revealed no substantive disadvantages with regard to tumor-related and surgical factors in the patients with cirrhosis compared with the patients without cirrhosis. The recurrence-free survival rates after minor and major resection indicated fewer disadvantages of limited hepatectomy in the group with cirrhosis than in the group without cirrhosis. Moreover, the recurrence-free survival of the group with cirrhosis was shorter at less advanced stages than at more advanced stages when compared with that of the group without cirrhosis. CONCLUSIONS: The higher carcinogenic potential in cirrhosis could be presumed to be the most likely reason for the poorer prognosis after surgery in the patients with HCC and cirrhosis.

The prognostic significance of surgical margin in liver resection of patients with hepatocellular carcinoma.

OBJECTIVE: To evaluate the prognostic significance of surgical margin in liver resection of patients with hepatocellular carcinoma. DESIGN: Retrospective study. SETTING: The Center for Adult Diseases, Osaka, Japan, between 1980 and 1989. PATIENTS: One hundred eighty-five patients with hepatocellular carcinoma who underwent liver resection with complete extirpation. MAIN OUTCOME MEASURE: Cumulative survival rate. RESULTS: The patients were divided into a wide surgical margin group, in which the lesion was excised with a margin of 1.0 cm or more, and a narrow surgical margin group, in which the margin was less than 1.0 cm. No significant differences could be detected in survival rates for 3 years or longer. Mean +/- SE tumor sizes were 3.4 +/- 0.4 cm and 4.4 +/- 0.3 cm, respectively, in the wide and narrow surgical margin groups. The patients were divided into three groups according to tumor size: group 1, 2.0 cm or less in diameter; group 2, greater than 2.0 cm but 5.0 cm or less in diameter; and group 3, greater than 5.0 cm in diameter. In groups 2 and 3, no significant differences in survival rates were found between the wide and narrow surgical margin groups. In group 1, the survival rate was significantly higher in the wide surgical margin group than in the narrow surgical margin group (P < .05). CONCLUSIONS: Small hepatocellular carcinomas of 2.0 cm or less in diameter should be resected with an adequate surgical margin. However, surgical margin was not a significant factor in the resection of hepatocellular carcinomas larger than 2.0 cm.

CT findings in primary osteosarcoma of the jaw.

Findings of computed tomography (CT) in five patients with osteosarcoma of the jaw are presented. CT played an important role in the assessment of the tumour extent before the planning of treatment for both primary and recurrent jaw osteosarcoma. Plain CT was capable of demonstrating subtle bony change (cortical reaction and calcification) and medullary tumour extension without interference from other superimposed bones. Tumour vasculature was well represented by thin-slice CT scan with intravenous bolus injection of contrast medium. We emphasize the importance of preoperative CT scanning from both a radiological and surgical point of view when confronted with a tumour of the maxilla or mandible.

Acute lymphoblastic leukemia associated with a t(1;19)(q23;p13) in an adult.

A cytogenetic study of a 38-year-old patient with acute lymphoblastic leukemia (ALL) revealed a t(1;19)(q23;p13), which is a characteristic translocation of childhood ALL. The leukemic cells were positive for the CD10, CD19, HLA-DR, TdT and cytoplasmic mu-chain. Both of the immunoglobulin heavy chain gene loci were rearranged and the RNA-based polymerase chain reaction demonstrated the E2A/PBX1 fusion transcript which is the result of the t(1;19). This finding suggests that the t(1;19) is implicated not only in childhood ALL but also in adult ALL patients.

Simple and low-cost tele-nuclear medicine conference system with the e-mail protocol.

PURPOSE: Because of the recent innovative growth in computer technology, digital imaging, and the Internet, we can take advantage of these facilities for education and clinical work in nuclear medicine. We developed a tele-nuclear medicine conference system with electronic mail (e-mail) on the Internet. METHODS: Twenty-one physicians (20 radiologists, 1 neurologist), 6 technologists and 2 medical students in six university hospitals (Japan 5, Canada 1), 5 local hospitals in Japan participated in this project. We used digital still cameras (330 k pixels) equipped with a floppy disk drive and 10 x optical zoom to digitize images with JPEG compression (640 x 480 matrix). The images were attached to e-mail messages (containing a brief description of each case). The mail was sent simultaneously to all members on the mailing list. Scintigram and SPECT images as well as other radiological images were sent by e-mail. Reply mails about each case were sent to all members via the mailing list. RESULTS: During a period of 6 months, 18 cases (tumor/infection: 7, bone: 6, cardiovascular: 1, neurology; 3, endocrine: 1) with 144 e-mails (average 5.6/case) were submitted to the conference. The average period of discussion was 15.6 days. The number of attached images was 1 to 9 (average, 4.2/e-mails). JPEG compression rate was 1/10 to 1/20. The quality of the images was good enough for discussion. Some cases required additional images for further discussion. CONCLUSION: Our tele-nuclear medicine conference with an electronic mailing list and digital camera was simple and low-cost. The conference system was useful for education and clinical work.

Increased heme oxygenase-1 gene expression in the livers of patients with portal hypertension due to severe hepatic cirrhosis.

Surgical bleeding associated with splanchnic hyperaemia due to portal hypertension complicates the anaesthetic management of hepatic transplantation. Although the mechanism(s) of portal hypertension are not fully understood, carbon monoxide, a product of the heme oxygenase (HO) reaction, is thought to be one of the endogenous vasodilators in the liver. In this study, the expression of mRNA encoding inducible HO isozyme (HO-1) in the livers of patients with portal hypertension undergoing hepatic transplantation was determined in comparison with those without portal hypertension. HO-1 mRNA levels were significantly greater in the portal hypertension group than in the group without portal hypertension. In contrast with HO-1, the gene expression of non-specific delta-amino-levulinate synthase (ALAS-N), which is down-regulated by heme in the liver, was the same in both groups. These results suggest that HO-1 is up-regulated through heme-independent stimuli according to the development of portal hypertension, and that induced HO-1 plays a pathophysiological role in portal hypertension through carbon monoxide production.

Human slow cortical potential in association with voluntary jaw movements.

The distribution of a readiness potential (RP), i.e., a negative-going slow cortical potential (SCP) preceding the onset of voluntary movements, was studied in association with self-paced voluntary jaw-closing and jaw-opening movements in 4 healthy human subjects. A negative-going SCP starting at ca.1.5-2.0 s preceding the onset of the self-paced jaw-opening and jaw-closing movements was found at all the recorded sites of Fz, Cz, Pz, F3, F4, F7, F8, C3, C4, T3 and T4. The RP was maximum in amplitude at Cz (ca.8microV), although there was no significant difference between Cz and either C3 or C4; it was smaller at T3 and T4 than at any of Fz, Cz, Pz, C3, and C4. The polarity, amplitude, and time course of the RP in association with jaw movements was virtually the same as those associated with voluntary unilateral extension of the middle finger, except for a contralaterally-dominant side asymmetry between C3 and C4 in the latter. There was neither rapidly increasing negative potential (NS') in the RP recorded from any site, nor bilateral difference in the RPs coinciding with unilateral biting of a gauze pad. It is suggested that the motor cortex would be activated bilaterally in coordination even in the case of unilateral biting.

[Intramural injection of anticancer emulsion by gastroendoscopy].

Attempting to establish a topical chemotherapy for stomach cancer, injectable 5-FU emulsion (O/W type) has been developed. The distribution of 5-FU was analyzed by the procedures of quantification and X-rays. The combination of lipiodol having a contrast ability in the oil phase was studied. During the endoscopic examination before operation, 1.0 ml of 5-FU was injected at a site, a total of 50 ml at 2 to 4 sites in the submucosal tissue of the lesion. From the result of examination of 5-FU distribution in the extracted stomach and lymph node, it was confirmed that the drug was retained at the site of injection. In addition, 0.017-0.056 microgram/g on the average of 5-FU concentration was transferred to the secondary lymph node. At the same time, its distribution was monitored by X-rays. In those cases which received intermittent administration for twice or more before operation, the 5-FU concentration was detected at a higher rate than in cases receiving a single dose. This suggests that the therapy is markedly effective for stomach cancer and its metastasis to the lymph node as topical therapy.

[Chemoembolization for liver metastasis from colorectal cancer].

Chemoembolization using Lipiodol, cisplatin, angiotensin II and Gelfoam (modified sandwich therapy) was carried out for the patients with liver metastasis from colorectal cancer. 1. Ten of 30 patients who underwent hepatic resection received TAE before operation, and the remaining 20 underwent surgery without preoperative TAE. Three-year survival of the former was 66%, and that of the latter was 44% (not significant). 2. Twenty-two patients who were assessed as non-resectable were surgically catheterized into the hepatic artery. Thirteen patients received TAE (totally 38 times) and intra-arterial infusion chemotherapy, and the remaining 9 underwent intra-arterial chemotherapy alone. The 50% survival of the former and the latter was 545 and 285 days, respectively. One year survival of the former was significantly better than that of the latter. 3. Fourteen patients had intrahepatic recurrences after hepatic resections. Eight patients received TAE and the remaining 6 did not. The 50% survival of the former was 615 days and that of the latter was 190 days. For one-year survival, the former was significantly better than the latter. These results suggested that TAE is an effective modality for liver metastasis from colorectal cancer.

[Intraarterial and intraportal chemotherapy combined with decollateralization for cholangiocellular carcinoma and metastatic liver cancer].

Two patients with cholangiocarcinoma and one patient with liver metastasis from inflammatory breast cancer underwent catheterization into both hepatic artery and portal vein following decollateralization using silicone rubber sheeting. They received arterial chemoembolization and chemotherapy and portal chemotherapy through the catheters repeatedly. Two patients with cholangiocarcinoma are still alive more than one year after the beginning of the treatments without regrowth of the tumors. The patient with metastatic liver cancer died of lung metastasis, although the liver foci were controlled by procedure. Thus, both intraarterial and intraportal chemotherapy combined with decollateralization by silicone rubber sheeting seems to be effective for advanced cholangiocarcinoma and metastatic carcinoma.

[Long-term postoperative courses of hepatocellular carcinoma with and without cirrhosis].

Until the end of August 1988, 158 patients with hepatocellular carcinoma underwent curative hepatic resection in our department. One-hundred and twenty-one patients (77%) had liver cirrhosis (Group A), and the remaining 37 (23%) did not (Group B). Background factors and postoperative courses were compared between Group A and Group B. With regard to clinical stage and curability, there were no significant differences between the two groups. On postoperative follow-up on 1- to 5-year survival, no differences were recognized between the two groups, but on and after 6-year survival, the former were significantly worse than the latter. The main cause of death was cancer in both groups. In group B, all intrahepatic recurrences happened within 3 years after surgery. On the other hand, intrahepatic recurrences of Group A were also found on postoperative 4- and 5-year to be as numerous as the recurrences found at 1-, 2- and 3-year after surgery. Moreover, with recurrent cases on and after 4 years in Group A, the frequency of solitary focus was high. The differences of postoperative courses between these two groups might be caused by metachronous carcinogenesis of cirrhotic liver.

[Percutaneous ethanol injection therapy (PEIT) and transarterial embolization (TAE) for recurrent hepatocellular carcinoma--report of 2 cases].

Two patients with recurrent hepatocellular carcinoma underwent reoperation following percutaneous ethanol injection therapy (PEIT) and transarterial embolization (TAE). In the first case, although the nodules where the accumulation of Lipiodol (LpD) was seen showed complete necrosis, viable cancer cells were seen in the areas with slight accumulation of LpD. One nodule with no accumulation of LpD where PEIT seemed to have been performed, developed necrosis. In the second case, the nodules with LpI) accumulation also showed almost complete necrosis. The area where PEIT was performed was mixed with necrosis and bleeding, where a small viable cancer nodule existed. The reason for incomplete anticancer effects by PEIT seemed to be the too small ethanol injection.

["Wrapping therapy" for advanced hepatic cancer with arterial and intraportal infusion chemotherapy].

A new treatment method to intercept collaterals using silicone rubber sheeting was used for 5 patients with advanced hepatic cancer. The therapy was carried out to prevent new collaterals. This procedure was followed by arterial chemoembolization, arterial infusion chemotherapy and intraportal infusion chemotherapy. The results were complete response in 2 patients, partial response in 2 patients, and no change in 1 patient. The overall survival time was 7-54 months after wrapping. Although a randomized control study is necessary to assess the true value of this method, the new therapy is considered worth using as an adjuvant treatment for advanced hepatic malignancies uncontrolled by arterial chemotherapy or chemoembolization.

[Regional therapy to prevent recurrence after surgery in hepatocellular carcinoma].

The significance of regional therapy to prevent recurrence after surgery for hepatocellular carcinoma (HCC) was evaluated. In 275 patients who underwent hepatic resection for HCC, 143 (52%) had recurrences. Post-recurrence survival of the patients with regional therapy for recurrent foci was significantly better than that of patients without such therapy. Five-year post-recurrence survival of the patients treated with second surgery (77%) was significantly better than that of patients treated with chemoembolization (17%). The difference in 5-year survival between the former and the latter seemed to be caused by the difference in the degree of tumor progression at the recurrence. A second hepatic resection was the treatment of choice for a solitary intrahepatic recurrent tumor. However, chemoembolization was recommended for two or more recurrent foci.

[Effects of craniofacial pain on jaw jerk in man].

Jaw jerk was evoked in 12 normal subjects (N group) and 12 patients with unilateral craniofacial pain who had neither mandibular deviation nor organic changes in the temporomandibular joint (P group), about every ca. 2 sec by tapping the center of the chin with a reflex hammer, in which a microswitch was embedded to indicate the time of its contact with the chin. The surface electromyogram of the masseter muscle was recorded bilaterally. It was found that (1) in the N group, there was no difference in the onset latency between the right (6.30 +/- 1.06 ms; n = 192) and left (6.32 +/- 1.04 ms; n = 192) sides (P > 0.05); (2) in the P group, the latency was shorter on the painful side than on the pain-free side; and (3) after pain was relieved by treatment, the bilateral difference in the latency of jaw jerk disappeared, and the latencies fell to that in normal subjects. It was concluded that the bilateral difference of the latency of jaw jerk can be used as an investigative criterion for the existence of pain.

[The assessment of preoperative transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC)--the comparison between "whole-liver" TAE and "lobar or segmental" TAE].

In 180 patients with hepatocellular carcinoma (HCC) who underwent radical hepatectomy, 52 patients were received preoperative arterial chemoembolization (TAE) for the whole liver (whole-liver TAE group: group A), 39 for the limited area of the liver (lobar or segmental TAE group: group B) and the remaining 89 had no treatments before surgery (control group: group C). In order to evaluate the significance of preoperative TAE, long-term prognoses were compared among the three groups. Although there were no significant differences in survivals between A and C, the 2- and 6-year survivals in group B were significantly better than those in group C (P less than 0.05). With regard to reduction rates of tumors and necrotizing effect for daughter nodules after TAE, the lobar or segmental TAE was significantly superior to the whole-liver TAE. Moreover, the lobar or segmental TAE deteriorated the liver function significantly less than the whole-liver TAE. These findings suggest that the lobar or segmental TAE is more advantageous than the whole-liver TAE as a preoperative adjuvant therapy.

[Changes of serum interleukin 6 (IL6) and acute phase protein after hepatectomy in patients with chronic liver disease].

We examined the changes in serum levels of interleukin 6 (s-IL6) and acute phase protein (APP) during perioperative periods in patients with or without chronic liver disease (CLD) who underwent hepatectomy or other surgeries. The elevation of s-IL6 on the first postoperative day was only correlated with preoperative values of indocyanine green retention test (ICG-R15) (r = 0.56, p < 0.01), and not concerned with any operative factors. We divided the patients into the following three groups; the patients with CLD undergoing hepatectomy (n = 21, group A), the patients without CLD undergoing hepatectomy (n = 7, group B), and the patients without CLD undergoing surgeries other than hepatectomy (n = 7, group C). The values of s-IL6 on preoperative day, 1st, 4th, and 7th days after surgery in group A were significantly higher than the corresponding values in group C (p < 0.05). Among the hepatectomy groups, the serum levels of APP on the 4th day after surgery were significantly higher than those on preoperative day. We concluded that the changes in s-IL6 after hepatectomy were strongly concerned with preoperative liver function, especially with values of ICG-R15. However, it seemed that the induction of APP was negatively correlated with the preoperative liver function.

[Postoperative change of serum protease inhibitor and C-reactive protein level--with special reference to surgical resection of liver cirrhosis].

Changes in the activities of blood protease inhibitors and acute-phase reactive substances during surgical resection of liver cirrhosis were investigated by measuring the pre- and postoperative blood concentrations of alpha 1-antitrypsin (alpha 1AT), alpha 2-macroglobulin (alpha 2MG), pancreatic secretory trypsin inhibitor (PSTI), urinary trypsin inhibitor (UTI) and C-reactive protein (CRP), in patients with liver cirrhosis who underwent hepatectomy (Group A, n = 19), those without liver cirrhosis who underwent hepatectomy (Group B, n = 6) and those without liver cirrhosis who underwent surgeries other than hepatectomy (Group C, n = 5). On examining the preoperative blood levels of protease inhibitors, Group A had an increased level of alpha 2MG and a decreased level of UTI compared to Groups B and C. alpha 1AT and CRP began to increase on the first day following hepatectomy and formed peaks on the third postoperative day. The increases were significantly higher in Group B than Group A (p less than 0.01). To investigate factors causative of these differences, alpha 1AT and CRP on the third postoperative day were compared in relation to the time of operation, amount of intraoperative bleeding, weight of the resected liver and preoperative ICGR15. alpha 1AT and CRP were significantly correlated to only preoperative ICGR15. PSTI was increased postoperatively but showed no difference between Groups A and B.