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The effect of blood volume contraction induced by a 4-week regimen of spironolactone (100 mg/day) or furosemide (40 mg/day) on the hepatic venous pressure gradient (HVPG), an indicator of portal hypertension, was evaluated in patients with cirrhosis and no ascites. In the spironolactone group (n = 15), HVPG decreased significantly from 16.5 +/- 0.9 mmHg (mean +/- S.E.M.) to 12.9 +/- 1.0 mmHg (P0.005) and total blood volume contracted significantly from 4338 +/- 231 ml to 4006 +/- 203 ml (n = 14, P0.01). Although the HVPG changes did not correlate significantly with changes in measured total blood volume or in simultaneously determined systemic haemodynamics, a significant inverse correlation (r = -0.74, P0.01, n = 12) was found between the HVPG change and posttreatment plasma aldosterone levels, attesting to the effectiveness of spironolactone therapy in lowering HVPG. In the furosemide group (n = 10), neither HVPG (13.7 +/- 0.3 mmHg vs. 13.6 +/- 0.9 mmHg) nor total blood volume (4961 +/- 153 ml vs. 4964 +/- 162 ml) declined significantly. These results show that long-term administration of spironolactone to patients with cirrhosis and no ascites produced a significant reduction in HVPG that may have been due to gradual, sustained volume contraction. Thus, spironolactone may prove to be an effective treatment for portal hypertension in cirrhosis without ascites.

Atrial fibrillation (AF) is the most common form of tachyarrhythmia and carries a significant risk of serious thromboembolic complications. Anticoagulation is used for long‐term thromboprophylaxis and for short‐term management in a number of clinical situations, among which is the medical or electrical cardioversion of AF to sinus rhythm. Current guidelines recommend prompt cardioversion with heparin cover for AF of < 48 h duration, and several weeks of warfarin therapy prior to cardioversion when the duration of disease is longer. Recent animal and human studies, however, have shown that swifter cardioversion is likely to be more successful in achieving sinus rhythm and in reducing the risk of recurrence of AF. Other observations have demonstrated that thrombi can develop within a few hours of the development of AF. These considerations suggest that cardioversion should be carried out as early as possible in all cases, and that the most sensitive means of detecting atrial thrombi, currently transesophageal echocardiography (TEE), should be used to screen all patients prior to cardioversion. Within this context, there is growing interest in the use of low‐molecular‐weight heparin (LMWH) as an anticoagulant therapy in AF. Compared with unfractionated heparin, LMWH therapy does not involve prolonged intravenous administration, hospitalization, or laboratory monitoring; LMWH therefore has the potential to greatly simplify anticoagulation therapy for AF, especially pericar‐dioversion. Recent studies have demonstrated that LMWH can be used safely and effectively in place of unfractionated heparin for acute treatment at the onset of AF and during early cardioversion. For example, in patients with AF, a strategy of immediate administration of dalteparin (100 IU/kg s.c. twice daily) continued for 11 days, combined with early TEE and immediate cardioversion in patients with no thrombus, resulted in sinus rhythm in 74% of patients after a median of 7 days. Low‐molecular‐weight heparin therapy may also find a role perioperatively and in selected patients, notably those with warfarin intolerance, as a replacement for warfarin following cardioversion. Controlled clinical studies are still required, however, to establish a firm, evidence‐based foundation for the use of LMWHs in AF.

Twenty-three patients with HBe antigen-positive chronic hepatitis B were treated with capitalite first letters Maruyama (SSM). HBe antigen turned negative in 15 patients. The levels of various cytokines in pre- and post-treatment frozen serum samples from six patients whose HBe antigen turned negative and from five whose HBe antigen did not were examined. Reduction of serum interleukin (IL) -10 level to below 20 pg/ml was observed after SSM treatment in four of the six patients whose HBe antigen turned negative. SSM was found to stimulate the production of interferon (IFN) -gamma in peripheral blood cells from two healthy volunteers. This stimulatory effect was confirmed in 12 out of 24 healthy volunteers. SSM augmented the production of IFN-gamma in eight out of 10 patients with chronic hepatitis B and nine of 10 with hepatitis C. These results demonstrate for the first time that SSM stimulates the production of IFN-gamma in human peripheral blood cells and also suggest that treatment of HBe antigen-positive chronic hepatitis B patients with SSM leads to the clearance of HBe antigen and normalization of serum aspartate aminotransferase levels through inhibition of IL-10 and stimulation of IFN-gamma.

Shiga toxin, produced by Escherichia coli O157:H7, is important for the pathogenicity of the epidemic form of hemolytic uremic syndrome (HUS). This toxin has recently been found to stimulate endothelin-1 synthesis in cultured endothelial cells in vitro.We investigated endothelin and cytokine levels in sera during a large outbreak of E. coli O157:H7 infection in Osaka, Japan, in 1996. Eleven patients with HUS and 9 patients with hemorrhagic colitis at the onset of E. coli O157:H7 infection were studied.Serum IL-6 (p0.01), IL-8 (p0.05), IL-10 (p0.001) and endothelin (p0.001) levels were significantly increased in patients with HUS compared to those with colitis only. The serum thrombomodulin level, a molecular marker of endothelial damage, also showed a significant positive correlation with serum IL-6 (p0.01), IL-8 (p0.01), IL-10 (p0.01) and endothelin (p0.001) levels. In a HUS patient, the increase in serum IL-10 and endothelin levels reached a plateau prior to the peak of serum creatinine levels.Increased serum endothelin synthesis by Shiga toxin in vivo was proven in HUS secondary to E. coli O157:H7 infection. Increased serum endothelin and IL-10 levels were speculated to be associated with the development of HUS through vascular endothelial damage caused by E. coli O157:H7 infection.

We report a rare case of glomerulocystic kidney disease (GCKD) with congenital hypothyroidism. A gigantic abdominal mass was noted at birth. There was no family history of renal cystic disease. Ultrasonography revealed diffuse granular cysts in the markedly enlarged kidneys. Blood examination showed moderate renal failure and hypothyroidism. Bilateral nephrectomy was conducted at 47 days of age to relieve respiratory failure and severe abdominal distention caused by the growing cystic kidneys. Histological findings of the kidney showed numerous glomerular cysts without renal dysplasia. There were no other malformations. These findings were compatible with GCKD.

Hypophosphatasia is associated with a defect of the tissue-nonspecific alkaline phosphatase (TNSALP) gene. The onset and clinical severity are usually correlated in hypophosphatasia; patients with perinatal hypophosphatasia die approximately at the time of birth. In contrast, we describe a male neonatal patient with hypophosphatasia who had no respiratory problems and survived. He was compound heterozygous for the conversion of Phe to Leu at codon 310 (F310L) and the deletion of a nucleotide T at 1735 (delT1735), causing the frame shift with the result of the addition of 80 amino acids at the C-terminal of the protein. Because the C-terminal portion of TNSALP is known to be important for TNSALP to bind to the plasma membrane, the localization of wild-type and mutated TNSALP proteins was analyzed using green fluorescent protein chimeras. The expression vectors containing the complementary DNA of fusion proteins consisting of signal peptide, green fluorescent protein, and wild-type or mutated TNSALP, caused by delT1735 or F310L mutation, were introduced transiently or stably in Saos-2 cells. The delT1735 mutant failed to localize at the cell surface membrane, whereas the wild-type and the F310L mutants were located in the plasma membrane and cytoplasm. The assay for enzymatic activity of TNSALP revealed that the delT1735 mutant lost the activity and that the F310L mutant exhibited an enzymatic activity level that was 72% of the normal level. The F310L mutation was also detected in another neonatal patient with relatively mild (nonlethal) hypophosphatasia (reported in J Clin Endocrinol Metab, 81:4458-4461, 1996), suggesting that residual ALP activity of the F310L mutant contributes to the less severe phenotype. The patient is unique, with respect to a discrepancy between onset and clinical severity in hypophosphatasia.

Bone marrow stromal cells (BMSCs) are a heterogeneous population of cells derived from colony-forming units-fibroblastic (CFU-Fs). These cells reside in the bone marrow cavity and are capable of differentiating into several cell phenotypes including osteoblasts, chondroblasts, hematopoiesis-supporting stromal cells, and adipocytes. However, the factors that regulate the proliferation and differentiation of the BMSC population are for the most part unknown. Since many members of the receptor tyrosine kinase (RTK) family have been shown to participate in growth control of various mesenchymal cell populations, in this study we examined the expression and function of RTKs in the BMSC population. Degenerate oligonucleotides corresponding to two conserved catalytic domains of the RTK family and RT-PCR were used initially to determine which RTKs are expressed in the human BMSC (hBMSC) system. After subcloning the amplification product generated from mRNA of a multicolony-derived hBMSC strain, PDGF receptor (beta), EGF receptor, FGF receptor 1, and Axl were identified by DNA sequencing of 26 bacterial colonies. Furthermore, PDGF and EGF were found to enhance BMSC growth in a dose-dependent manner and to induce tyrosine phosphorylation of intracellular molecules, including the PDGF and EGF receptors themselves, demonstrating the functionality of these receptors. On the other hand, bFGF was found to have little effect on proliferation or tyrosine phosphorylation. Since single colony-derived hBMSC strains are known to vary from one colony to another in colony habit (growth rate and colony structure) and the ability to form bone in vivo, the expression levels of these RTKs were determined in 18 hBMSC clonal strains by semiquantitative RT-PCR and were found to vary from one clonal strain to another. While not absolutely predictive of the osteogenic capacity of individual clonal strains, on average, relatively high levels of PDGF-receptor were found in bone-forming strains, while on average, nonbone-forming strains had relatively high levels of EGF-receptor. Taken together, these results indicate that RTKs play a role in the control of hBMSC proliferation, and that the differential pattern of RTK expression may be useful in correlating the biochemical properties of individual clonal strains with their ability to produce bone in vivo.

Background: A large number of mutations of the tyrosinase gene result in oculocutaneous albinism (OCA). Therefore, at present, sequence analysis of the tyrosinase gene has become necessary to diagnose OCA patients and their relatives. Objective: The aim of this study was to facilitate the sequence-based diagnosis of tyrosinase-related OCA by using small amounts of the patient’s blood. Methods: Blood spots dried on filter papers were used as sources of genomic DNA. The exons and flanking regions of the tyrosinase gene were amplified by polymerase chain reaction (PCR) and were directly sequenced in both directions. Results: We successfully amplified all exons of the tyrosinase gene by PCR and were able to characterize compound heterozygous mutations of R278X and +ΔC310 in the patient’s gene. Conclusion: Recent advances of PCR-related technology allowed us to use fairly limited samples of blood for sequence analysis of the tyrosinase gene.

To enhance the portal hypotensive effect of nonselective beta-blockers, combinations of vasoactive agents with different mechanisms should be considered. The effect of carvedilol (CAS 72956-09-3, Artist), and alpha-/beta-blocking agent, on hepatic and systemic hemodynamics in 10 patients with portal hypertension was evaluated. After administration of carvedilol, the hepatic venous pressure gradient (HVPG) decreased from 15.9 +/- 3.2 mmHg to 13.3 +/- 4.0 mmHg (mean +/- SD) at 60 min (-15%) and to 12.9 +/- 3.0 mmHg at 90 min (-17%, p0.05). However, only 5 patients showed a decrease of HVPG by more than 20% at 60 or 90 min. The estimated hepatic blood flow (EHBF) was not significantly reduced. In contrast, heart rate (-8%, p0.05), mean arterial pressure (-10%, p0.01), and cardiac index (CI) (-8%, p0.05) were all reduced at 90 min, while total systemic vascular resistance was not altered. The reduction of HVPG was significantly correlated with the decrease of CI (r = 0.6415, p0.05). The portal hypotensive effect of carvedilol may mainly result from a reduction of CI. However, because of the greater reduction of HVPG than that of CI, other additive actions were suggested.

Nine pediatric patients (mean age, 10 years) with biliary atresia, who had hypoxemia related to intrapulmonary shunting, underwent living related liver transplantation. The effects of hypoxemia during the early postoperative period after liver transplantation on cardiopulmonary and renal function, as well as on transplanted liver, were analyzed. Based on the degree of shunt ratio calculated by technetium-99m macroaggregated albumin scintigraphy, the nine patients were included in the moderate group (shunt ratio under 40%, n=4) or the severe group (shunt ratio over 40%, n=5). Partial pressure of arterial oxygen was maintained at normal range in the moderate group, while that in the severe group persistently had very low values (50 mmHg), in spite of a high degree of oxygen supply. However, all patients in the severe group maintained stable cardiopulmonary vital signs, including systemic blood pressure, heart rate, respiratory rate, and cardiac index. They also demonstrated stable renal function. None of the patients died of cardiopulmonary or renal insufficiency after transplantation, but three patients died of portal vein thrombosis, sepsis, and intracranial hemorrhage (one each). The minimal adverse effect of hypoxemia on the transplanted liver was confirmed by a rapid increase of arterial ketone body ratio, low peak values (under 200 IU/L) of aspartate aminotransferase, and a steady decrease of serum total bilirubin. Four patients encountered surgical complications, including two bile leaks from the cut liver surface, two leaks from bilioenteric anastomosis, and one intestinal perforation. Six patients suffered from bacterial infections, including four wound infections, three right subphrenic abscesses, one cholangitis, and two systemic sepses. All patients in the moderate group recovered from hypoxemia, but four of five patients in the severe group have not recovered during the follow-up period between 4 and 9 months. It was concluded that the adverse effects of hypoxemia on cardiopulmonary and renal function and transplanted liver were minimal, so that patients with severe hypoxemia could tolerate the stress of liver transplantation without special management. However, the high incidence of surgical complication and infection suggested the adverse effects of hypoxemia on wound healing and resistance to bacteria infection.

In living-related liver transplantation, a portion of the whole liver, usually the left lateral segment or the left lobe, is harvested for use as the graft liver. A relatively small graft may twist around the hepatic venous anastomosis, causing outflow blockage. After an initial experience of such a complication in the early post-transplantation period in one case, we began to apply a tissue expander to obliterate the dead space left after emplacement of a relatively small graft. Commercially available tissue expanders, ordinary employed in plastic surgery, were used for five pediatric recipients (6-14 yr old) whose ratio of graft weight to recipient body weight ranged from 0.74 to 1.72. The expander, filled with 240-350 ml saline, was put into the space to the right of the graft. Aspiration of the expander content was started after the 5th-7th postoperative day (POD), at a rate of 50 ml of fluid a day. The expanders were taken out on the 11th-14th POD after complete removal of the content. Complications observed in the five cases were right shoulder pain (5/5), fluid collection after removal of the expander(2/5), chylous ascites (1/5), and one instance of bile leakage. All the complications were successfully managed and controlled conservatively. There was no outflow obstruction detected by Doppler ultrasonography before or after removal of the expander. This is a simple and safe method for preventing the early onset of outflow block after partial liver transplantation.

The effects of three FK506 induction regimens on pediatric living-related liver transplantation (LRLT) were studied retrospectively in terms of patient survival and adverse side effects. The patients consisted of 120 children, ranging from 3 to 210 months of age, who underwent a total of 122 LRLTs with a minimum follow-up of 6 months. Immunosuppression consisted of FK506 and low-dose steroids. FK506 was given in 3 ways: (1) high-dose intravenous (i.v.) induction, with FK506 begun at a dose of 0.15 mg/kg/day for the first 16 patients; (2) low-dose i.v. induction, with FK506 begun at a dose of 0.06 mg/kg/day for the next 45 patients; and (3) per os (p.o.) induction, with FK506 begun orally from the day prior to LRLT and continued postoperatively. Whole-blood trough levels of FK506 were monitored daily. Trough levels in the high induction group were often as high as 100 ng/ml compared with the level of 20 ng/ml in the p.o. induction group. Patient survivals were 75%, 89%, and 80% in the high-i.v. vs. low-i.v. vs. p.o. groups. The incidences of acute rejection were 12.5%, 22.2%, and 26.4%, and the incidences of viral infection were 56%, 38%, and 11% in the respective groups. Major adverse effects occurred with higher frequency in the high-i.v. induction group. Oral FK506 induction therapy at a dose of 0.15 mg/kg/day starting from the day before LRLT was safer and associated with a lower incidence of viral infection than therapy with i.v. FK506.

We report a case of leiomyosarcoma whose origin was near the root of ileocecal mesentery and extended into the retroperitoneum. Preoperative imaging examination, including CT, MRI and angiography clearly displayed its origin and retroperitoneal extension. These results contributed to treatment planning.

To study the long-term effects of pharmacological combination therapy, a comparison was made of the haemodynamic changes in patients with cirrhosis and portal hypertension following a 4-week treatment of propranolol or nipradilol, a new nonselective beta-blocker with nitrovasodilating effect. Nipradilol (12 mg/dag, n = 12) significantly diminished wedged hepatic venous pressure (WHVP, 25 +/- 16%), the hepatic venous pressure gradient (HVPG, 20 +/- 12%), and estimated hepatic blood flow (EHBF, 18 +/- 16%). Propranolol (30 mg/day, n = 11) also caused a significant reduction in WHVP (22 +/- 21%) and HVPG (24 +/- 21%), but not in EHBF. The percentage of portal pressure reduction and the frequency of nonresponders did not differ between the nipradilol and propranolol groups. Both agents reduced heart rate by approx. 20%. Nipradilol, however, did not cause a significant reduction in cardiac index (CI) versus a 14% reduction by propranolol. Pulmonary capillary wedge pressure and central venous pressure, an index of preload, were decreased slightly in the nipradilol group. When nonresponders were excluded, there was a significant correlation of the percentage of reduction between WHVP and CI or systemic vascular resistance, in the nipradilol group. These results indicate that nipradilol may have potent hypotensive effects on portal hypertension, similar but not superior to propranolol. Nipradilol, at the dosage used in the present study, did not appear to exert a nitrovasodilating effect to enhance the portal pressure reduction induced by beta-blocking action.

The influence of thoracotomy and laparotomy on the chest wall movement was examined using newly produced 6-channeled linear magnetometer. Two groups (one is the group of the patients who had undergone thoracotomy and laparotomy for esophageal cancer and the other is the group of the patients who had undergone laparotomy) were examined 2 to 8 weeks after operation. The chest wall movement was restricted analward at the operative wound of the chest wall. The other points had no remarkable restriction. From the view point of the chest wall movement this study shows thoracotomy and laparotomy at the same time and only laparotomy had almost the same influence.

The efficacy of coronary venous versus left atrial administration of superoxide dismutase was studied in 24 open chest pigs which had 60 min of left anterior descending coronary artery occlusion followed by 3 h reperfusion. The pigs were randomly assigned to three treatment protocols: group A (n = 8) superoxide dismutase (5 mg kg-1) was infused into the great cardiac vein for 30 min beginning 15 min before reperfusion; group B (n = 8) superoxide dismutase (5 mg kg-1) was infused into the left atrium in a similar manner to group A; group C (n = 8) bovine serum albumin (5 mg kg-1) was infused into the great cardiac vein in the same manner as group A. Infarct size, expressed as percent of area at risk, was significantly smaller in group A (28.2 +/- 13.0%) than groups B (58.7 +/- 8.3%) and C (61.6 +/- 7.2%) (P less than 0.05). The results indicate that retroinfusion of superoxide dismutase into the great cardiac vein before reperfusion may be an effective treatment for the prevention of reperfusion injury, even in the absence of a well developed coronary collateral circulation. Antegrade (left atrial) administration of the same amount of superoxide dismutase did not decrease infarct size in pigs. The most likely explanation for this difference in efficacy is that drug delivery with left atrial administration is dependent on antegrade flow with reperfusion which is less reliable and less efficient than coronary venous retroinfusion. The latter provides a predictably high concentration of superoxide dismutase to the jeopardized myocardium during the period of ischaemia before reperfusion.

Small bowel infarction following abdominal aortic reconstruction is extremely rare, and the prognosis remains poor. This report describes a 65-year-old man with small bowel infarction after resection of an abdominal aortic aneurysm. He was successfully treated with resection of the ischemic segment from the distal duodenum to the mid-small bowel and construction of a duodenoileostomy. The postoperative course was uneventful.

The effect of plasma volume contraction induced by a 4-wk administration of spironolactone or furosemide on the hepatic venous pressure gradient was evaluated in consecutively allocated patients with cirrhosis and no ascites. In the spironolactone group (n = 15), the hepatic venous pressure gradient decreased significantly (p less than 0.005), by 21.8%, with a significant contraction of circulating plasma volume (p less than 0.01). Although there were no statistically significant correlations between the change in hepatic venous pressure gradient and changes in circulating plasma volume or in simultaneously determined systemic hemodynamics, a significant negative correlation (r = -0.74, p less than 0.01, n = 12) between the hepatic venous pressure gradient change and the post-treatment plasma aldosterone levels was found. However, in the furosemide group (n = 10), the hepatic venous pressure gradient and circulating plasma volume did not significantly decrease. Our data demonstrated a significant reduction in the hepatic venous pressure gradient on a chronic administration of spironolactone, which may have been due to volume contractions in patients with cirrhosis and no ascites.

Using a 6-channeled linear magnetometer, the chest wall movement of the esophageal cancer patients was measured before operation. The patients were divided into two groups. Group A: measured value of the bilateral chest wall movement was equal. Group B: measured value of the chest wall movement was different. (One side of the chest wall movement was restricted.) Two groups were compared with several factors in pre-, intra-, post-operation. Two groups had difference in thickness and adhesion of the pleura, operation time, bleeding volume on thoracotomy, lymph nodes metastasis to intrathoracic region, and staging by lymph nodes metastasis. (Group B had larger value in these factors.) The result suggests that the restriction of the chest wall movement was caused by the adhesion of the pleura.

The effects of diltiazem on hemodynamics, plasma catecholamine and plasma renin activity were studied during treadmill exercise test in 9 cases with moderate essential hypertension. Diltiazem of 120 mg/day was orally administered for 4 weeks. At maximum exercise, significant decrease in systolic blood pressure (-32 mmHg), heart rate (-16/min), pressure-rate product (-7,883 mmHg/min), plasma norepinephrine (-195 ng/L) and plasma epinephrine (-11 ng/L) were observed; while, diastolic blood pressure, ST depression and plasma renin activity showed no significant change. Also, a significant correlation between systolic blood pressure and plasma norepinephrine (r = 0.57, p0.001), especially after diltiazem therapy (r = 0.68, p0.001), was observed. These findings indicated that diltiazem can reduce the secretion of catecholamine from the sympathetic nerves during exercise in patients with essential hypertension.

Rat bone marrow stromal cells were cultured in vitro. At days 14–15 of culture, dense clusters of polygonal cells were formed, and they mineralized 2–3 days later. The cells resembling osteoblasts or young osteocytes were histologically observed to be embedded in mineralized or unmineralized extracellular matrices of the nodules. Next, these mineralized nodules were electron-microscopically examined. The osteoblastic cells associated with the nodules had a well-developed rough endoplasmic reticulum, an evident Golgi apparatus and some mitochondria as their intracellular organellae. Some lysosomes and microfilaments were also visible in the cytoplasms. Moreover, some cells protruded cell processes toward the neighboring cells through the extracellular matrix. The extracellular matrix consisted of numerous collagen fibrils which were striated with 60–70 nm axial periodicity and which was similar to bone tissue collagen. A large number of matrix vesicles were scattered among the collagen fibrils in the unmineralized area of the nodules. In contrast, in the mineralized area, numerous matrix vesicles at different stages of maturation and many calcified spherules were observed. That is the mineralization in this culture system was considered to be initiated in association with the matrix vesicles and to progress along the collagen fibrils. From these findings, it was confirmed by the present study that the mineralized nodules formed in this bone marrow stromal cell culture were ultrastructurally similar to bone and that the mineralization also proceeded by going through the normal calcification process. This culture system is considered to be available to study osteogenic differentiation and calcification mechanisms.

76 year-old man was transferred to emergency room because of severe epigastralgia and dyspnea. He was well until 5 hours before admission, when he suddenly felt severe epigastralgia followed by vomiting. He was found to be in warm shock state. Chest X-ray film showed dilation of mediastinum, pneumo mediastinum, left pleural effusion and subcutaneous emphysema, which were consistent with esophageal perforation. Esophageal contrast study was diagnostic. Emergency operation was performed in which rupture of the lowest esophagus causing remarkable mediastinitis and pleuritis was observed. Esophageal tear was primarily closed and chest drains were placed. Despite severe post-operative complications, he was discharged with recovery 5 months later.

In 102 patients with ischemic heart disease the severity of stenosis was classified into 7 grades (0, 25, 50, 75, 90, 99, 100%) in accordance with the AHA reporting system. The coronary angiograms were compared at first and second catheterization (intervals 2-84 months) and progression was considered present if the stenosis in the second study showed more than one grade increase in comparison with the first study. Fifty six patients met criteria for progression. Risk factors were obtained within the first second catheterization. Drug and diet therapy were evaluated by interview. No significant difference could be found between the progression (P) group and the nonprogression (N) group in relation to family history and obesity. A history of hypertension was more common in the P group. In respect to blood sampling, the values of total cholesterol, Apo B, CII, E and Apo B/AI were significantly higher in the P group than those in the N group at first and second catheterization. The percentage of patients showing abnormal levels of blood sugar and lipid were higher in the P group than the N group although the percentage of patients with drug and diet therapy were higher in the P group than in the N group. The percentage of patients with diet therapy for hyperglycemia and hyperlipidemia were higher in the P group, however weight increase was more common in the P group. These data suggest that sufficient diet and drug therapy is necessary for patients with risk factors.

The effect of changes in body posture on estimated hepatic blood flow (EHBF) and various hemodynamic parameters was examined in 15 patients with compensated cirrhosis. EHBF and various hemodynamic parameters were first measured with the patients in the supine position, and then again 10 min after tilting to 45 degrees. EHBF was 1089 +/- 315 ml/min at supine and 1065 +/- 328 after tilting; the difference was not significant. However, the patients were then divided into two groups according to the magnitude of the decrease in EHBF after tilting, with those showing a decrease of 10% of more assigned to group B, and those showing a decrease of less than 10% assigned to group A. It was found that ICG (R15) and BSP (R45) were significantly higher in group A. Meanwhile, among hepatic and systemic hemodynamics, wedged hepatic venous pressure, hepatic venous pressure gradient, free hepatic venous pressure, cardiac index, systolic blood pressure, systemic vascular resistance, and stroke volume were found to have changed significantly after tilting. These results suggest that posture change has no effect on EHBF in compensated cirrhotic patients.

A phyllodes tumor of the breast can grow into an extremely large oncoides occasionally and be a cause of poor prognosis without adequate treatment in some cases. A case of giant phyllodes tumor which is thought to be one of the largest and heaviest among reported cases in Japan was treated in our clinic. The process of enlargement of the tumor and the treatment of this patient are reported.

Mitomycin C conjugated with dextran (MMC-D), with a molecular weight of about 500,000, was synthesized for intraoperative topical application. MMC-D contained approximately 10% mitomycin C (MMC) and released active MMC by hydrolysis with a half-life of 24 hours in vivo. In experimental studies, MMC-D was retained at the injection site for about 48 hours and transferred to the lymphatic system. Sixteen patients suffering from advanced abdominal cancers were treated with MMC-D (5-10mg eq. MMC) by intraoperative direct injection or percutaneous injection under sonography. Objective tumor responses were observed in 9 of 16 cases. No serious side-effect was observed other than temporary fever, localized pain and mild leukopenia. MMC-D diffused from the center of the tumor releasing active MMC which was transferred to the lymphatic system. Local application of MMC-D was therefore considered to be effective for the treatment of solid tumors.

Healing process of anastomosis and its procedure were studied in following points: Four-interrupted sutures anastomosis in the Wistar rats revealed recanalization without leakage in 64 out of 69. Lymphangial recanalization through the anastomosis was completed within 21 days after operation by Gambee' layer-to-layer anastomosis. While 8 weeks were required by everted or inverted anastomosis. Serosal surface of invaginated intestinal segment of which length corresponded to x1-x2 luminal diameter in the telescoping anastomosis was covered within 8 weeks by the proliferated mucosae of the both proximal and distal segments. Telescoping anastomosis was found to be useful to make an intestinal valve which worked just the same as ileocoecal junction. IVH and elementary diet were effective on the healing of anastomosis. According to the above mentioned findings, following operative procedures were recommended: Esophago-jejunal conduit duodenostomy following total gastrectomy. Choledocho-jejunal conduit duodenostomy with the intestinal valve as bile duct reconstruction. Construction of the intestinal valve and an artificial sphincter using rectus abdominis muscle fibers for ileostomy or short bowel syndrome. Endorectal pull-through operation for anterior-resection of the rectum as well as for radical treatment of Hirschsprung' disease.

Accompanying surgical resection of the primary tumor is removal of its drainage lymph nodes. However, all of the minute regional lymph nodes cannot be identified and some may be left behind. If a certain anticancer agent in the form of an emulsion is injected topically into the lymph nodes, it may suppress the lymphatic metastases. Domestic rabbits were used as experimental animals, because transplantable VX2 tumors are available. The vermiform appendix was selected as the transplantation site because of its rich supply of lymph follicles, simulating lymph nodes histologically, and because the path of lymph drainage is very simple. The drainage lymph node, which is located at the root of the appendix, was selected for study. The rate of transfer of bleomycin into lymph nodes and of its sustained release from the nodes was extremely enhanced by the use of a sphere-in-oil-type emulsion--more than two times higher than in the use of a W/O emulsion. Although prolongation of survival time did not take place in animals receiving the bleomycin solution topically or intravenously, five of the seven rabbits receiving the local administration of bleomycin as a sphere-in-oil or a water-in-oil emulsion, between which differences were not found in tumor effects, survived with complete reduction of the lymph node metastases.

The use of vitamin E as a protective agent against adriamycin-induced toxicity in CDF1 and BDF1 mice resulted in potentiation of the chemotherapeutic index of adriamycin. A single dose of 15 mg of adriamycin per kg body weight produced a significantly reduced mean survival time. A dosage of adriamycin of 15 mg per kg body weight was employed in the following experiments. In P388 ascites tumor-bearing mice, four consecutive injections of several doses of vitamin E before injection of adriamycin produced a significant prolongation of the mean survival. In concomitant studies of serum tocopherol content, 7 to 10 micrograms/ml appeared to be an appropriate serum concentration, in accordance with the result of our previous report on its immunopotentiation effect. alpha-tocopherol seemed to have a two- to three-fold greater physiological activity than alpha-tocopheryl acetate. Dietary vitamin E treatments offered no protection against adriamycin toxicity, because the serum tocopherol content reached only 4.39 micrograms/ml in mice given the vitamin E-sufficient feed in this study. The results suggested that an increase of the serum tocopherol level to about two to three times the untreated control would be required before the adriamycin treatment to reduce its toxicity.

The effects of percutaneous transluminal coronary angioplasty (PTCA) on left ventricular function at rest and during stress test were examined. Effect of PTCA at rest We studied 10 patients who fulfilled the following criteria, 1) single vessel disease, 2) high grade stenosis in the left anterior descending artery, 3) successful PTCA, 4) no restenosis, 5) without electrocardiographic evidence of previous myocardial infarction, and 6) technically adequate left ventriculograms in both pre and post PTCA studies. Follow-up studies were done six months after PTCA. Filling fraction as an index of early diastolic function was significantly lower than that of normal controls. There were no significant changes in left ventricular end-diastolic pressure, peak dp/dt, negative peak dp/dt, ejection fraction, left ventricular systolic pressure/end-systolic volume, between pre- and post-PTCA studies. Filling fraction in a jeopardized area, which was supplied by the left anterior descending artery, increased significantly after PTCA. No significant change was observed in the inferior area. Effect of PTCA during stress test A contrast stress test in eight successful cases without restenosis was performed by injecting 0.7 ml per kilogram of contrast material (76% urografin) at a rate of 13 ml/sec into the left ventricle before and six months after PTCA. The left ventricular end-diastolic pressure increased to 20.1 +/- 3.8 mmHg during stress test before PTCA, and only to 14.3 +/- 5.3 mmHg after PTCA (difference highly significant). Before the procedure, negative peak dp/dt during stress test was 1782 +/- 358 mmHg/sec; it increased significantly to 2342 +/- 702 mmHg/sec after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical results of intraoperative radiotherapy for gastric cancer were reported. One hundred and five cases of gastric cancer were treated by intraoperative radiotherapy. Indications for the intraoperative radiotherapy were determined as follows: 1) The primary lesion (tumor) located at the level of gastric corpus or antrum (M, A); 2) At least, the primary tumor should be resected; 3) Neither liver metastasis nor peritoneal dissemination was noticed; 4) Lymph node metastasis were limited to the second group (less than N3); 5) Cases of which tumor-infiltration-depth reached to the serosal surface (S3) of the posterior gastric wall and infiltrated to the pancreatic capsule were included. However, infiltrations to the serosal surface of the anterior gastric wall were not subjected to the treatment, because of having peritoneal disseminations. Irradiation of 2800-4000 rad of electron beam from betatron was performed after resection of the stomach and the regional lymph node as possible. Five-year survival rate was studied on 58 cases (consisting 5 cases of stage I, 27 cases of stage II, 12 cases of stage III and 14 cases of stage IV). Comparisons were done with the cases receiving surgical operation only.Whatever the stage of the patient was, 3-year survival rate was found to be better in the radiotherapy group than that of the control group (treated surgical resection only). Five year survival rate of the stages III and IV in the radiotherapy group was better than the control group. Unfavorable side effects were observed in 4 cases out of 105 cases. In one case, penetration of postoperative peptic ulcer into the irradiated aortic wall was found by autopsy. Two cases of bile duct stenosis and one case of ileus due to acutely developed peritonitis carcinomatosa were experienced. In conclusion, intraoperative radiotherapy immediately after surgical resection for the treatment of gastric cancer was found to be an effective method. The most effective application of the method appears to be to cases of stage II and III without liver metastasis and peritoneal disseminations (H0P0, M, A).

The human tumor colony-forming assay was used to compare chemosensitivity among tumor cells within a primary tumor, between primary tumor and its metastasis, and between different metastases. The results indicate that the reported discrepancies of in vitro and in vivo results in clinical trials with TCFA for predicting of resistance or sensitivity to cytostatic drugs may be due to therapeutic heterogeneity among tumor colony-forming units within a primary tumors and between primary tumor and metastases, and that the results from a metastatic lesion may have more profound implications in planning treatment of other metastatic lesions of the same patient.