Superior mesenteric artery syndrome with vascular calcification in a maintenance hemodialysis patient.

INTRODUCTION: Superior mesenteric artery (SMA) syndrome is defined as trapping of the third portion of the duodenum between the SMA and the aorta. In this case, vascular calcification associated with dialysis might have contributed to the onset of SMA syndrome. CASE: The patient was a 74-year-old woman who had been receiving maintenance hemodialysis. She developed sudden onset of severe recurrent vomiting during admission for pseudo-gout. CT of the abdomen revealed duodenal obstruction with an abrupt cutoff in the third portion of the duodenum, and dilatation of the first and second portions of the duodenum. The aortomesenteric angle was significantly sharp. In addition, severe vascular calcification was revealed in the SMA and aorta. The initial treatment was decompression of the obstruction by a nasogastric tube and parenteral nutrition for the management of fluid and electrolyte imbalance. She recovered with only conservative treatment. CONCLUSION: Vascular calcification of the SMA and aorta might have contributed to compression of the third portion of the duodenum. Vascular calcification associated with dialysis could be a factor in SMA syndrome.

Regulation of dihydropyrimidine dehydrogenase and pyrimidine nucleoside phosphorylase activities by growth factors and subsequent effects on 5-fluorouracil sensitivity in tumor cells.

Dihydropyrimidine dehydrogenase (DPD) and pyrimidine nucleoside phosphorylase (PyNPase) are the first and rate-limiting enzymes that regulate 5-fluorouracil (5-FU) metabolism, and tumoral DPD activity appears to be a promising predictor of 5-FU sensitivity. However, the regulatory mechanisms determining these enzyme activities have not been fully understood. We investigated the biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on cell growth and tumoral DPD and PyNPase activities, and the subsequent effects on 5-FU sensitivity in uterine cervical carcinoma SKG-IIIb cells. The treatment of tumor cells with EGF or TGF-alpha resulted in a concentration-dependent increase in tumor cell growth and PyNPase activity, whereas tumoral DPD activity was inhibited. Their stimulatory effects on tumor cell growth correlated well with PyNPase activity, but were inversely related to DPD activity (P < 0.01). 5-FU sensitivity of tumor cells increased in the presence of EGF or TGF-alpha. These growth factors were shown to stimulate the first, rate-limiting enzyme activity in 5-FU anabolism and to inhibit that in 5-FU catabolism, leading to enhancement of the antiproliferative action of 5-FU at achievable therapeutic levels. The tumor environmental factors, EGF and TGF-alpha, may act as intrinsic regulators of DPD and PyNPase activities that affect the 5-FU sensitivity of individual tumors.

Studies on the carcinogenicity of potassium iodide in F344 rats.

A chronic toxicity and carcinogenicity study, in which male and female F344/DuCrj rats were given potassium iodide (KI) in the drinking water at concentrations of 0, 10, 100 or 1000 ppm for 104 weeks, and a two-stage carcinogenicity study of application at 0 or 1000 ppm for 83 weeks following a single injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN), were conducted. In the former, squamous cell carcinomas were induced in the salivary glands of the 1000 ppm group, but no tumors were observed in the thyroid. In the two-stage carcinogenicity study, thyroidal weights and the incidence of thyroid tumors derived from the follicular epithelium were significantly increased in the DHPN+KI as compared with the DHPN alone group. The results of our studies suggest that excess KI has a thyroid tumor-promoting effect, but KI per se does not induce thyroid tumors in rats. In the salivary gland, KI was suggested to have carcinogenic potential via an epigenetic mechanism, only active at a high dose.

Low susceptibility of Long-Evans Cinnamon rats to N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis and inhibitory effect of urinary copper.

We studied the susceptibilities to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis of male Long-Evans Cinnamon (LEC), F344 and Long-Evans Agouti (LEA) rats. Male rats (n=21) were given 0.1% BBN in their drinking water from week 6, 8 and 10 for one week, and killed in week 56. The incidences of transitional cell tumors (papillomas plus carcinomas) in BBN-treated LEC and F344 rats were 12% and 76%, respectively (P<0.001, experiment 1), and those in LEC and LEA rats were 11% and 95%, respectively (P<0.001, experiment 2). When male LEC and F344 rats were given 0.1% BBN in their drinking water for 7 days, the intake of BBN and the urinary concentration of its active metabolite, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), were higher in the LEC rats (P<0.01). The urinary pHs of untreated LEC and F344 rats were similar between week 6 and 30. The urinary copper concentration was lower in LEC rats before jaundice than in F344 rats, but its concentrations in 28- and 50-week-old LEC rats were 1.7 and 2.3 times those in F344 rats. In a two-stage carcinogenesis study using F344 rats, i.p. injections of cupric nitrilotriacetate increased urinary copper excretion, and inhibited BBN-induced bladder carcinogenesis. In a two-stage carcinogenesis study using LEC rats, oral administration of D-penicillamine decreased urinary copper excretion, and increased BBN-induced bladder cancer, although the difference was not significant. These data show that LEC rats are resistant to bladder carcinogenesis and suggest that urinary copper has a significant role in their resistance.

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 13). Effects of a single oral dose of cyclophosphamide.

As part of a collaborative effort to evaluate whether effects on male reproductive organs of chemicals can be detected within two-week in toxicity studies, eight-week-old male Sprague-Dawley rats were given a single oral administration of 100 mg/kg of Cyclophosphamide (Cp), and sacrificed at 1, 3, 7 and 14 days thereafter. The numbers of seminiferous epithelial cells were counted in the seminiferous tubules of stages II-III, V, VII and XII of the spermatogenic cycle. Animals showed decreased spermatogonia at Day 3, decreased spermatogonia and preleptotene spermatocytes at Day 7, and decreased spermatogonia and zygotene spermatocytes at Day 14. We also detected decrease of zygotene spermatocytes on careful routine/traditional histopathological examination at Day 14. These results suggest that the testicular toxicity of Cp can be detected within two weeks after treatment with a sufficient dose in rats.

Effect of CABG on coronary flow reserve in atresia of the left coronary ostium.

We evaluated the change of coronary flow reserve using a Doppler guidewire before and after coronary artery bypass grafting to assess the coronary hemodynamic effect of surgical revascularization in a 13-year-old boy with congenital atresia of the left coronary ostium, which is one of the rarest of the congenital coronary anomalies. Coronary flow reserve in the right coronary artery and left anterior descending artery increased significantly after coronary revascularization, and a microvascular bed developed in the left anterior descending artery.

Effects of D-galactosamine hydrochloride and partial hepatectomy on spontaneous hepatic injury and hepatocarcinogenesis in Long-Evans Cinnamon rats.

To examine the effect of nongenotoxic chemicals on hepatocarcinogenesis in Long-Evans Cinnamon (LEC) rats, we gave 6-week-old male and female LEC rats (n = 18) weekly subcutaneous injections of D-galactosamine hydrochloride (GalN, 300 mg/kg) in 0.9% NaCl or only 0.9% NaCl for 50 weeks, and killed them in week 62. GalN-treated male rats unexpectedly showed no lethal necrotizing hepatitis. GalN treatment increased the incidence of cholangiofibrosis in males and its severity in females, but did not cause significant increases of hepatocellular tumors in either sex. GaIN treatment increased the 5-bromo-2'-deoxyuridine (BrdU)-labeling index of hepatocytes and plasma hepatocyte growth factor, and accelerated megalocytic alterations without reduction of the hepatic copper concentration. Next, male and female LEC rats were subjected to two-thirds partial hepatectomy (PH) or sham hepatectomy in week 8 (n = 12) or in week 14 (n = 9), and killed in week 62. PH in week 14 inhibited lethal hepatitis, but PH in week 8 was less effective. PH reduced the hepatic copper concentration to half that of controls. The present data suggest that induction of hepatocyte regeneration by repeated injections of GalN, or by PH just before the onset of jaundice has a significant effect in prevention of hepatic injury of LEC rats, but not enhancement of spontaneous hepatocarcinogenesis.

Role of copper accumulation in spontaneous renal carcinogenesis in Long-Evans Cinnamon rats.

Spontaneous renal cell tumors in totals of 223 male and female Long-Evans Cinnamon (LEC) rats of 51-120 weeks old, 157 male F344 rats of 51-120 weeks old, and 14 male Long-Evans Agouti (LEA) rats of 51-70 weeks old were examined histologically. The incidences of renal cell tumors increased with age in male and female LEC rats, but no tumors developed in F344 or LEA rats. Dilated atypical tubules of the kidneys were observed at high incidence in aged LEC rats. Copper staining of LEC rat kidneys showed a positive reaction in proximal tubules of the cortex and the outer stripe of the medulla. The renal copper concentration of LEC rats reached a peak in the period of necrotizing hepatitis with renal tubular necrosis, and was higher than that in F344 rats for up to 106 weeks. In contrast, the renal iron concentration of LEC rats was lower than that in F344 rats except in the period of necrotizing hepatitis. Long-term treatment of LEC rats with D-penicillamine, a copper-chelating agent, inhibited accumulation of copper, but not iron, in the kidneys, and inhibited the development of karyomegaly of proximal tubules and dilated atypical tubules. These results suggest that persistent copper accumulation after toxic necrosis of tubules is the major cause of spontaneous renal carcinogenesis in LEC rats.

[Effects of prophylactic antibiotic agent on interleukin-6 level in open chest surgery--comparison between imipenem and flomoxef].

Cytokines are known to increase in the patients subjected to open chest surgery. Those patients are usually administered with antibiotic agents for prophylaxis, while some of antibiotic agents might yield significantly higher level of cytokines than other agents especially in patients suffering from severe infections. It is believed that imipenem may yield lower interleukin-6 (IL6) level than cephem antibiotics. To study whether such difference could be observed in the patients who show no sign of severe infections, a total of 13 patients underwent scheduled open chest surgery were allocated at random into two groups, the imipenem-group and the flomoxef-group. The cytokine levels of the patients in the two groups were compared, while the prophylactic administration of imipenem or flomoxef. In both groups, IL6 increased immediately after the operation while endotoxin remained unchanged. Thereafter IL6 decreased gradually in both groups, however, the decrease of IL6 in the imipenem-group was faster and greater than the flomoxef-group resulting in the significantly lower level of IL6 on the 4th day after operation. One week after the operation, there existed no difference in the IL6 levels between these two groups. In conclusion, it was suggested that, depending on the choice of a prophylactic antibiotic agent, some invasive burden could be added to those patients underwent open chest surgery, a certain number of whom would develop severe infection.

Induction of squamous cell carcinomas in the salivary glands of rats by potassium iodide.

In a 2-year carcinogenicity study of potassium iodide (KI) in F344/DuCrj rats, squamous cell carcinomas (SCCs) were observed in the salivary glands of 4/40 males and 3/40 females receiving 1000 ppm KI in the drinking water. Ductular proliferation with lobular atrophy was observed at high incidence in the submandibular glands of the high-dose animals, and squamous metaplasia was frequently evident within the proliferative ductules and the larger interlobular ducts. A transition from metaplasia to SCC was apparent. The results suggest that squamous metaplasia in proliferative ductules, occurring secondarily to lobular impairment induced by KI, may develop into SCCs via a non-genotoxic, proliferation-dependent mechanism.

[A case of successfully treated fungal tricuspid infective endocarditis with repeated pulmonary embolism].

A case of successfully treated fungal tricuspid infective endocarditis with repeated pulmonary embolism is reported. A 60-year-old man had received along term intravenous hyperalimentation for the treatment of the complication after hepatopancreatoduodenectomy, associated with Candida sepsis. He was once discharged, successfully treated with antifungal agents. But he was readmitted to our hospital due to fever, cough and chest pain. Blood culture revealed Candida tropicalis. Pulmonary scintigraphy and angiography revealed multiple infarcts of the right lung, and echocardiography showed vegetation on the tricuspid valve. Because of exacerbation of shortness of breath, tricuspid valvuloplasty and thromboembolectomy in the pulmonary arteries was performed. Postoperative course was uneventful and he had a marked improvement of dyspnea after operation.

Lack of carcinogenicity of cyanoguanidine in F344 rats.

The carcinogenicity of cyanoguanidine, a compound used in the production of melamine, guanidine salts and guanamine derivatives, was examined in male and female Fischer 344 rats fed CRF-1 pulverized diets containing 0, 2.5 and 5% cyanoguanidine for up to 2 yr. The rats were randomly allocated to three groups, each consisting of 50 males and 50 females. The mean body weight gains in both sexes of the 5% group and in females of the 2.5% group were significantly lower than the control values after wk 1 of treatment. No other signs of toxicity were seen in any of the rats throughout the treatment period. Histopathologically, various tumours developed in all groups, including the control group, but these were all similar to those known to occur spontaneously in this strain of rats, and no toxicologically significant increase was found for any lesion type in the treated groups. On the basis of these results, it is concluded that cyanoguanidine exerts no carcinogenic potential in F344 rats when administered for up to 2 yr under the conditions of the present study.

UDP-GT involvement in the enhancement of cell proliferation in thyroid follicular cell proliferative lesions in rats treated with thiourea and vitamin A.

The mechanisms underlying enhanced cell proliferation in thyroid proliferative lesions of rats simultaneously treated with large amounts of vitamin A (VA) and thiourea (TU) were investigated. Male F344 animals were initiated with N-bis(2-hydroxypropyl)nitrosamine (2800 mg/kg body weight, single s.c. injection). Starting 1 week later, groups received water containing 0.2% TU (TU group), diet containing 0.1% VA (VA group), both 0.2% TU and 0.1% VA (TU + VA group) or tap water/basal diet without supplement (control group) for 10 weeks. The serum levels of triiodothyronine (T3) and thyroxine (T4) were decreased and the thyroid stimulating hormone (TSH) levels were elevated in the TU and TU + VA groups, with the degree of change being significantly greater in the combined treatment group. The induction of P450 isoenzymes by TU was not enhanced by VA supplementation, but uridine diphosphate glucuronosyltransferase (UDP-GT) activity in the liver was significantly increased in the TU + VA group compared to the TU group. Thyroid weights were increased in both the TU and TU + VA groups, this being more pronounced with VA supplementation. Thyroid follicular cell hyperplasias and neoplasias were induced to similar extents in both TU treated groups, but their cell proliferation appeared to be increased by the VA supplementation. The results of the present study suggest that enhanced cell proliferation is due to increased TSH stimulation, resulting from the decrease in serum T3/T4 levels brought about by induction of liver UDP-GT activity with the combined action of TU + VA as well as inhibition by TU of thyroid hormone synthesis in the thyroid.

In vitro combination effect of 5-fluorouracil and cisplatin on the proliferation, morphology and expression of Ki-67 antigen in human gastric cancer cells.

The combination effect of 5-fluorouracil (5-FU) and cisplatin was examined in terms of the proliferation, morphology and expression of Ki-67 antigen, and propidium iodide (PI) staining using four cultured human gastric cancer cell lines, and we assessed how such activity was affected by the exposure time and the timing of treatment. MKN-1, MKN-28, MKN-45 and MKN-74 cells were exposed to various concentrations of 5-FU for 72 h and cisplatin for 8 or 72 h. At IC50, MKN-28 cells were more sensitive to 5-FU than other cell lines, whereas MKN-1 and MKN-45 cells were more sensitive to cisplatin than other cell lines. The cell growth-inhibitory activity of cisplatin was found to be 'area under the curve' dependent. When 5-FU and cisplatin were combined simultaneously, the combination effect was higher than that of 5-FU or cisplatin alone. On the other hand, when cisplatin was applied before 5-FU, there was no potentiation of the cell growth-inhibitory activity by combination treatment. In 5-FU-treated MKN-74 cells, the size, morphology and PI staining of nuclei were almost the same as those of the untreated cells, and the expression of Ki-67 antigen was less than that of the untreated cells. In cisplatin-treated MKN-74 cells, the size of cells and nuclei was larger than that of the untreated cells and fragmentation of nuclei was observed. The expression of Ki-67 antigen was less than the untreated cells but more than that of 5-FU-treated cells. In the cells treated with 5-FU and cisplatin in combination, the above changes were an intermediate of those of 5-FU-treated cells and cisplatin-treated cells. In conclusion, the cell growth-inhibitory activity of 5-FU and cisplatin against gastric cancer cells was potentiated by the combined treatment with 5-FU and cisplatin simultaneously, but not with cisplatin followed by 5-FU.

Effects of organic anions and bile acid conjugates on biliary excretion of LTC4 in the rat.

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, so-called canalicular multispecific organic anion transporter (cMOAT). On the other hand, a multiplicity of canalicular organic anion transport has been suggested. Therefore, to examine the substrate specificity of cMOAT using inhibition of excretion of [3H] LTC4-derived radioactive products in the bile as a marker, we examined the effects of various organic anions and bile acid conjugates on the biliary excretion of LTC4 in rats. Biliary excretion of the metabolites of [3H] LTC4, which was injected via the femoral vein, was markedly inhibited by sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, and ursodeoxycholate-3-O-glucuronide. In contrast, dibromosulfophthalein and cefpiramide slightly inhibited, and pravastatin, taurocholate, and 3,7-sul-UDC did not affect biliary LTC4 excretion. Furthermore, vinblastine and phenothiazine, a P-glycoprotein substrate and inducer, did not affect biliary LTC4 excretion. Among various organic anions and bile acid conjugates, LTC4, sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, and ursodeoxycholate-3-O-glucuronide may be good substrates for cMOAT.

[Clinical problems in surgical treatment for active infective endocarditis].

From October, 1982, to December, 1995, 22 patients with active infective endocarditis underwent surgical treatment. Of 22 patients, 12 patients (group P) demonstrated microorganisms on blood culture obtained at the operation and/or in the excised valve, and 10 patients (group N) showed acute inflammatory reaction in the excised valve microscopically. Operative mortality in group P was significantly higher than that in group N (50% versus 0%,p < 0.01). Especially in group P, five of six patients (83%) with uncontorolled infection for more than eight days died within 30 days of operation. This showed that prolonged preoperative periods of uncontrolled infection influenced the surgical outcome of active infective endocarditis. In conclusion, patients who do not promptly response to antibiotic treatment must be considered for early operation within seven days of the diagnosis of infective endocarditis to decrease operative mortality. The plasma level of CRP and definition of sepsis may be useful as indicators of uncontrolled infection.

[Surgical treatment for ascending aortic aneurysm using a transthoracic left ventricular venting].

Three patients with ascending aortic aneurysms underwent graft replacement using deep hypothermic circulatory arrest with continuous retrograde cerebral perfusion. In all three cases, preoperative radiographic examination revealed that the aneurysm was large, thin, and adherent to the back of the sternum. For this reason, left ventricular venting was performed through a left thoracotomy before median sternotomy, to decrease both the risk of rupture of the aneurysm and the difficulty of cannulation. This new method, called transthoracic left ventricular venting, was very useful for performing a median sternotomy under hypotensive and hypothermic conditions adequate to reduce the risk of rupture and to manage any rupture immediately through deep hypothermic circulatory arrest.

[Surgical treatment of incomplete endocardial cushion defect in adult patients].

Seven adult patients (> or = 40 years old) and six pediatric patients with incomplete endocardial cushion defect (ECD) underwent corrective surgery in our institution. Preoperative catheterization study showed that the left-to-right shunting rate and the pulmonary-to-systemic flow ratio were greater in adult patients than those in pediatric patients, but systolic pulmonary arterial pressure was not high and similar in the two groups. The degree of mitral regurgitation by left ventriculography was mild or moderate in both groups. However, in adult patients, a variety of arrhythmias were observed. Postoperatively, NYHA grades and arrhythmia improved markedly in the adult patients. Surgical correction for ECD is recommended even in adult patients before aggravation of cardiac failure and arrhythmia.

[Renal autotransplantation for dissecting aneurysm].

Out of twenty-five patients operated on for dissecting aneurysm in our institution since January 1991, four patients had autotransplantation of the kidney. The renal autotransplantation and the segmental replacement of the descending aorta with the prosthesis were done at the same time in three of them, and segmental replacement of the distal aortic arch was followed by autotransplantation because of the postoperative acute renal failure in the other one. Postoperative renal function of simultaneously operated patients was good whereas the patient who had been treated by two-staged operation needed hemodialysis for two weeks after the autotransplantation. Postoperative scintigraphy showed fully recovered function of the autotransplanted kidneys with enlargement. CT scan showed that the false lumen of the dissecting aorta was reduced in size with increased intraluminal clot formation. Renal autotransplantation with entry closure is easy and safe technique and assures successful operative results for the dissecting aneurysm, restoring impaired renal blood flow.

Effect of thyroid stimulating hormone on the development and progression of rat thyroid follicular cell tumors.

Time course changes in cell proliferative activity of thyroid focal hyperplastic and tumorous lesions as well as blood thyroid-related hormones in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN: 2800 mg/kg body weight, single s.c. injection) were examined following chronic administration of 0.1% sulfadimethoxine (SM) in the drinking water for 1, 4, 8, 12 and 16 weeks and at the end of a subsequent 4-week recovery period. Serum thyroid stimulating hormone (TSH) levels increased rapidly from week 1 of SM treatment, reaching a peak at week 8, and then decreased gradually with prolongation of treatment period, although remaining significantly elevated as compared with the corresponding controls at all time points up to week 16. Follicular cell hyperplasias and adenomas of the thyroid occurred from week 4 and carcinomas from week 8. All of these lesions showed high cell proliferative activities corresponding to high serum TSH levels during the early stage, but the levels in hyperplasias and adenomas decreased rapidly with prolongation of SM treatment. After the recovery period, serum TSH levels had returned to below the normal range and cell proliferation in follicular hyperplasias and adenomas had stopped or was very low. Some carcinomas demonstrating invasive growth also showed remarkable decreases in the cell proliferative activity. The results of our study strongly suggest that a high serum TSH level plays an important role in the early stage of thyroid tumorigenesis and that some tumors exhibiting invasive growth are still dependent on TSH stimulation.