Copper deficiency-induced pancytopenia after taking an excessive amount of zinc formulation during maintenance hemodialysis.

Erythropoiesis-stimulating agent (ESA) has been recognized as an effective way in the treatment of anemia due to chronic kidney disease, but we sometimes see intractable hemodialysis (HD) patients. The causes of ESA-resistant anemia in HD patients include deficiency of trace elements. We report the case of an 89-year-old male who developed pancytopenia after taking an excessive amount of zinc formulation for ESA-resistant anemia during maintenance dialysis. He was prescribed zinc acetate hydrate formulation about 6 months before his presentation. He was found to have pancytopenia 1 month before his presentation, at which point he was introduced to our hospital. We suspected a copper deficiency at the first visit and stopped zinc and added copper, and his condition subsequently improved without being handicapped. Zinc antagonizes copper, so we must take care to diagnose patients ingesting zinc supplements.

Relationship of aging and nutritional status to innate immunity in tube-fed bedridden patients.

BACKGROUND AND OBJECTIVES: Aging and malnutrition are known to influence immune functions. The aim of this study was to investigate the relationship of aging and malnutrition to innate immune functions in tube-fed bedridden patients. METHODS AND STUDY DESIGN: A cross-sectional survey was performed in 71 tube-fed bedridden patients aged 50-95 years (mean age±SD, 80.2±8.5 years) with serum albumin concentrations between 2.5 and 3.5 g/dL. We evaluated associations of age and nutritional variables with natural-killer cell activity, neutrophilphagocytic activity, and neutrophil-sterilizing activity. Nutritional variables included body mass index, weightadjusted energy intake, total lymphocyte count, and serum concentrations of albumin, transferrin, prealbumin, total cholesterol, C-reactive protein, and zinc. RESULTS: Natural-killer cell activity, neutrophil-phagocytic activity, and neutrophil-sterilizing activity were normal or increased in 67 (94%), 63 (89%), and 69 (97%) patients, respectively. Multiple linear regression analysis with a backward elimination method showed that natural-killer cell activity correlated negatively with aging and lymphocyte counts (p<0.01 for both) but positively with body mass index and transferrin (p<0.01 for both). Neutrophil-phagocytic and neutrophil-sterilizing activities were not associated with any variables. CONCLUSIONS: In tube-fed bedridden patients with hypo-albuminemia, natural-killer cell activity may be associated with aging, body mass index, transferrin, and lymphocyte counts.

Long-term enteral immunonutrition containing lactoferrin in tube-fed bedridden patients: immunological and nutritional status.

OBJECTIVE: The aim of this study was to examine the efficacy and safety of a novel immune-enhancing enteral formula, Prem-8, which contains lactoferrin as an immunonutrient. DESIGN, SETTING, PATIENTS: A multicenter, randomized controlled trial was conducted in 5 hospitals in Japan, and 71 tube-fed bedridden patients with serum albumin concentrations between 2.5 and 3.5 g/dL were allocated to Prem-8 (n = 38) or control formula (n = 33) groups for an observation period of 12 weeks. MEASURES OF OUTCOME: Efficacy was evaluated by comparing immunological (natural killer cell activity, neutrophil-phagocytic activity, neutrophil-sterilizing activity, and C-reactive protein), and nutritional (anthropometric measurements and serum levels of nutritional assessment proteins and total cholesterol) variables. Safety was assessed by comparing the incidence of adverse events. In a secondary analysis, patients were subgrouped according to the amount of protein supplemented (1 g/kg/d) so that immunological and nutritional variables and safety could be further compared. RESULTS: Natural killer activity and neutrophil functions were normal for both groups throughout the study period, without significant between-group differences at any point. Nutritional status was stably maintained in both groups, although the body mass index at 12 weeks was marginally lower in the Prem-8 group than in the control group (p < 0.01). The incidence of adverse events were comparable between both groups, but the incidence of fever in the Prem-8 group (7/14) was significantly lower than in the control group (10/11) in a subgroup of patients whose supplemented protein was less than 1 g/kg/d (p < 0.05). CONCLUSION: Prem-8 did not demonstrate superiority to the control formula with respect to immunological and nutritional variables, whereas the body mass index of patients in the Prem-8 group marginally decreased. However, Prem-8 had a favorable effect on the incidence of fever in a subgroup of patients with low protein intake.

Regulatory mechanism of silkworm hemocyte adhesion to organs.

Circulating hemocytes in the body fluid of the silkworm are increased during the larval-larval molting period. We investigated hemocyte adhesion to organs mediating the selectin-selectin ligands during the feeding period and the larval-larval molting period using the lectin staining method, sugar chain digestion test with glycoside hydrolases, and the hemocyte adhesion inhibition test using monosaccharides. The results of these tests suggested that the selectin ligand involved in hemocyte adhesion was the Sialyl Lewis x-type, and the structure was changed from the feeding period to the larval-larval molting period. Beta-galactosidase appears to be an enzyme that eliminates N-acetylgalactosamine and sialylated N-acetylgalactosamine from the terminal of Sialyl Lewis x. Beta-galactosidase activation in skin basement membranes, muscle, fat bodies, midguts, and hemocytes increased markedly during the larval-larval molting period, and at that time, hemocytes were detached from organs. Adding 20-hydroxyecdysone or its analog, tebufenozide to cultured fat bodies increased ß-galactosidase activity in these tissues. Therefore, 20-hydroxyecdysone may induce a structural change in Sialyl Lewis x type sugar chains on the cell surface of silkworm's organs by increasing the ß-galactosidase activity to detach hemocytes from organs and increase the number of circulating hemocytes during the larval-larval molting period.

Roles of the ether oxygen in hydration of tetrahydrofuran studied by IR, NMR, and DFT calculation methods.

We studied the concentration dependence of nu(C-H)'s in IR and (1)J(C,H) in NMR for binary water-tetrahydrofuran (THF) mixtures and found different trends for the two types of CH(2) groups in the five-membered ring. The changes of the nu(C-O) spectra showed that complexes of THF associated with water are formed, in which the number of water molecules increases with the water concentration. We suggested that hydration proceeds through the formation of 1:1, and 1:2 complexes of [THF:water] up to X(H(2)O) approximately 0.9, where X(H)((2))(O) is the mole fraction of the water in the mixtures. We carried out ab initio MO and DFT calculations to optimize the geometries of a THF dimer as a model of THF molecules in pure liquid, and 1:1 and 1:2 complexes of [THF:water] to simulate observed concentration dependence of nu(C-H)'s in IR and (1)J(C,H) in NMR. The changes of the calculated nu(C-H) spectra and (1)J(C,H) values for the optimized complexes are in agreement with those observed with varying X(H)((2))(O), supporting our proposal. From the vibrational and NBO analyses of the optimized complexes, the observed blue shift of nu(C-H)'s and the increase of (1)J(C,H) for the CH(2) groups neighboring to the ether oxygen were explained in terms of the changes in the stereoelectronic effect, resulting from HO-H...O< hydrogen bonding. The optimized 1:2-complex contains two weak C-H...OH(2) hydrogen bonds, and blue shift of nu(C-H)'s and increase of (1)J(C,H) were demonstrated from the same analyses of the complexes. This result of simulation also supports that the blue shift of nu(C-H)'s and increase of (1)J(C,H) observed for both the type of CH(2) groups at 0.6 X(H)((2))(O) < 0.9 are attributed to these interactions. On the basis of all these results, we propose that the formation of the 1:2-complex involving weak C-H...OH(2) hydrogen bonds is responsible dominantly for the hydrophobic hydration of THF.

Preservation of segment 4 inferior by distal middle hepatic vein reconstruction combined with extended right hepatectomy after portal vein embolization in a patient with a huge initially unresectable HCC.

An extended hepatectomy combined with preoperative portal venous embolization can offer curative resection in patients with initially unresectable hepatocellular carcinoma. However, hypertrophy of the future remnant liver is occasionally unsatisfactory after portal venous embolization in some patients to remove the initially unresectable tumor. In these patients, hepatic venous reconstruction to preserve hepatic parenchyma may contribute to the possibility of resection. The present case report shows a patient with an initially unresectable huge hepatocellular carcinoma in whom transarterial chemoembolization, portal vein embolization, and an extended right hepatectomy combined with distal middle hepatic venous reconstruction were performed to preserve Segment 4 inferior. The patient was a 66-year-old male. He presented with a huge hepatocellular carcinoma located at Segment 8, 7 and 4 superior, but the volume of the left lateral segment was only 267 mL. Transarterial chemoembolization was performed twice and right portal vein embolization was performed once, but the volume of the left lateral segment was only 318 mL compared to 487 mL which was a limit of future remnant liver volume. We therefore performed an extended right hepatectomy combined with distal middle hepatic venous reconstruction to preserve Segment 4 inferior. The left saphenous venous graft was used for this hepatic venous reconstruction. His postoperative course was almost uneventful. Postoperative abdominal computed tomography showed the satisfactorily preserved Segment 4 inferior. Distal hepatic venous reconstruction combined with an extended hepatectomy may further offer a chance of a curative resection for patients in whom enough hypertrophy of the future remnant liver is not obtained after portal venous embolization.

Celiac axis occlusion of a patient undergoing pancreaticoduodenectomy after distal gastrectomy.

In patients with celiac axis occlusion, performance of pancreaticoduodenectomy involves sacrifice of the gastroduodenal artery which results in a risk of hepato-pancreato-biliary and other organic ischemia. Celiac axis occlusion does not recently seem an uncommon finding in cases of pancreaticoduodenectomy but diagnosis of celiac axis occlusion may be difficult in patients with former abdominal surgery. The present case report shows a patient with pancreatic head adenocarcinoma, in whom a preoperative diagnosis of celiac axis occlusion was not proved because of displacement of the celiomesenteric arterial branches based on former distal gastrectomy with Kocher's maneuver. A 56-year-old man with malignant obstruction of the lower bile duct was referred to our hospital for undergoing pancreaticoduodenectomy. In his past history, the patient had undergone distal gastrectomy reconstructed with Billroth I method due to gastric ulcer. In preoperative abdominal angiography, the celiac axis was not detected at the normal position and was incorrectly recognized to be anomalously originated from the superior mesenteric artery. During surgery, hepatic arterial flow was markedly diminished by clamping of the gastroduodenal artery. Celiac axis occlusion was then proved and the thick and tight median arcuate ligament was detected. Hepatic arterial blood flow was recovered by a complete division of the median arcuate ligament. Postoperative course of the patient was uneventful. In cases of pancreaticoduodenectomy, careful preoperative angiographic diagnosis is needed for patients with celiac axis occlusion who have undergone former gastric surgery because the celio-mesenteric arterial branches have been displaced by Kocher's maneuver. The present report also demonstrates another patient with a typical celiac axis stenosis.

A patient undergoing pancreaticoduodenectomy in whom involved common hepatic artery anomalously arising from the superior mesenteric artery was removed and reconstructed.

Identifying anatomical variations of the celio-mesenteric arterial branches is important when performing pancreaticoduodenectomy. A relatively rare variation is the common hepatic artery entirely originated as a branch of the superior mesenteric artery. This type of variation is termed hepatomesenteric trunk type common hepatic artery, in which an accessory left hepatic artery arising from the celiac trunk is absent. Preservation of hepatomesenteric trunk type common hepatic artery is indispensable during pancreaticoduodenectomy because fatal hepatic injury or leak of hepaticojejunostomy can occur. The present case report shows a patient with pancreatic head tumor in whom hepatomesenteric trunk type common hepatic artery was involved by the tumor. The patient underwent pancreaticoduodenectomy during which the involved hepatomesenteric type common hepatic artery was removed and reconstructed using saphenous venous grafts. Histopathological examination showed double cancers which were composed of an advanced ductal adenocarcinoma of the pancreas and early bile duct adenocarcinoma. The patient is alive 18 months after the surgery without recurrence.

[Multicenter comparative study of the recurrence-inhibitory effect of oral fluoropyrimidine drugs in patients with colorectal cancer following curative resection].

HCFU and UFT were reported effective in adjuvant chemotherapy for colorectal cancer. This investigation was planned as a randomized study to compare the usefulness of combination therapies with mitomycin C (MMC)+HCFU and MMC+UFT as postoperative adjuvant chemotherapy in patients with colorectal cancer following curative resection, in terms of survival rate, recurrence rate, and adverse drug reactions. A total of 501 patients consisting of 252 patients with stage III/IV colon cancer (Colorectal Cancer Handling Rules, 4th Ed.) for which macroscopic curative resection was possible and 249 patients with stage II/III/IV rectal cancer (ibid, 4th Ed.) were registered from 40 participating institutions. The patients were randomly allocated to two groups with colon cancer and rectal cancer employed as stratification factors. Beginning on Day 14 after surgery, HCFU at 300 mg/day was administered to one group and UFT at 300 mg/day or 400 mg/day to another group, both orally and daily for one year. MMC 6 mg/m2 was administered intravenously to both groups on the day of surgery and the day following. Among the 501 patients, 496 patients (99%) were eligible. The 5-year survival rates were 77.1% for the MMC+ HCFU group and 79.2% for the MMC+UFT group, with the 5-year recurrence-free survival rates were 76.1% and 72.9%, respectively, neither showing a significant difference between the groups. Adverse drug reactions appeared in 23% of patients in the MMC+HCFU group and in 19% in the MMC+UFT group, with no serious reactions. One year after surgery the administration completion rates were good, at 82% for the MMC+HCFU group and 83% for the MMC+UFT group. No clear difference in effectiveness was noted between MMC+HCFU therapy and MMC+UFT therapy as postoperative adjuvant chemotherapy for colorectal cancer. The administration completion rates were good, and no serious adverse drug reactions were observed for either therapy. It was thus considered that both therapies could be administered safely, and both were useful as postoperative adjuvant chemotherapies for colorectal cancer. It is considered necessary to compare them with standard therapies in Western countries in the future.

[Evaluation of hepatic artery infusion chemotherapy for liver metastasis of colorectal cancer using a side-hole catheter].

In our department forty cases of hepatic artery infusion chemotherapy using a side-hole catheter were analyzed with liver metastasis of colorectal cancer from December 2000 to December 2003. This easily placed catheter is able to inject the agent effectively from the side hole. The efficacy of high dose 5-FU (1,000 mg/m2/week) of hepatic artery injected chemotherapy was evaluated. The catheter was inserted from femoral or the left subclavian artery, and the side hole positioned at the base of proper hepatic artery or common hepatic artery. This method resulted in catheter trouble only 18% of the time. As for arterial infusion chemotherapy, system management and an evaluation of the drug distribution is essential. The one-year survival rate was 71.9%, the 50% survival time was 23.4 months, and the response rate was 71%. In conclusion, this therapy was effective and useful for hepatic metastasis.

Low phosphorus tolerance mechanisms: phosphorus recycling and photosynthate partitioning in the tropical forage grass, Brachiaria hybrid cultivar Mulato compared with rice.

The Brachiaria hybrid cv. Mulato is well adapted to low-fertility acid soils deficient in phosphorus (P). To study the grassy forage's mechanisms for tolerating low P supply, we compared it with rice (Oryza sativa L. cv. Kitaake). We tested by using nutrient solution cultures, and quantified the effects of P deficiency on the enzymatic activities of phosphohydrolases and on carbon metabolism in P-deficient leaves. While P deficiency markedly induced activity of phosphohydrolases in both crops, the ratio of inorganic phosphorus to total P in leaves was greater in Brachiaria hybrid. Phosphorus deficiency in leaves also markedly influenced the partitioning of carbon in both crops. In the Brachiaria hybrid, compared with rice, the smaller proportion of (14)C partitioned into sugars and the larger proportion into amino acids and organic acids in leaves coincided with decreased levels of sucrose and starch. Hence, in P-deficient leaves of the Brachiaria hybrid, triose-P was metabolized into amino acids or organic acids. Results thus indicate that the Brachiaria hybrid, compared with rice, tolerates low P supply to leaves by enhancing sugar catabolism and by inducing the activity of several phosphohydrolases. This apparently causes rapid P turnover and enables the Brachiaria hybrid to use P more efficiently.

[Final results of a randomized clinical trial of adjuvant intraportal chemotherapy for colorectal cancer: Intraportal Chemotherapy for Colorectal Cancer Group].

The purpose of the present multi-center collaborative study was to elucidate the efficacy of intraportal chemotherapy with the combination of 5-FU and MMC for the prevention of liver recurrence after resection for colorectal cancer. A total of 125 patients with Stage II, III, and IV colorectal cancer were enrolled in this study between June 1993 and December 1995. Of them, 45 patients were randomized to a portal group: 10 mg/body of mitomycin one shot portal infusion, before and after 500 mg/m2 of 5-FU per 24 h for 7 days portal infusion followed by administration of oral 5-FU. Fifty-three patients were randomized to a control group: oral administration of 5-FU. Twelve patients suffered from temporary mild liver damage. One patient (2%) in the portal group and 6 patients (11%) in the control group developed liver metastases; there was not a significant difference between these two groups regarding development of liver metastases. There was also no significant difference by tumor stage between the portal and control groups regarding development of liver metastases. The 5-year survival rate and 5-year disease-free survival were 84.3% and 81.9%, respectively, in the portal group, and 70.7% and 72.4%, respectively, in the control group; the difference was not significant. Although there was not a significant difference between the portal and control groups regarding the prognosis in stage II, there was a significant difference between the portal and control groups regarding the 5-year disease free survival in stage III (81.1% vs 54.2%). These results suggest that intraportal chemotherapy is effective for stage III colorectal cancer.

Influence of perioperative blood transfusion on the prognosis of patients with gastric cancer receiving anticancer chemotherapy.

BACKGROUND: The deleterious effect of blood transfusions on survival has been reported in patients with cancers of various organs. However, it remains unclear whether there is any adverse effect of blood transfusion when the patients are administered anticancer drugs after surgery for gastric cancers.METHODS: Data from patients with gastric resection for advanced gastric cancer were retrospectively analyzed to determine the influence of perioperative blood transfusion on the survival rate. All patients were administered anticancer drugs (mitomycin C [MMC] and tegafur-uracil [UFT]). Sixty-nine (33%) of 208 patients received blood transfusion perioperatively, while 139 patients (67%) did not receive transfusion. Multivariate analysis of clinicopathologic prognostic factors, including blood transfusion, was performed. Lymphocyte subsets were measured to investigate the immunosuppressive effect of blood transfusion.RESULTS: The 5-year survival rate was 48.8% in the 69 transfused patients and 66.9% in the 139 non-transfused patients ( P < 0.01). Cox's multiple regression analysis showed that, when patients received anticancer drugs, perioperative blood transfusion was not a significant factor affecting survival after the gastric cancer surgery. However, the CD4/CD8 ratio at 3 months after the surgery was significantly lower in the transfused group than in the non-transfused group.CONCLUSION: Blood transfusion did not affect the survival of operated patients who received postoperative adjuvant chemotherapy. However, the finding that the ratio of CD4/CD8 after surgery was significantly higher in the non-transfused group than in the transfused group supports the notion that transfusion causes broad-spectrum immunosuppression.