Preserved seasonal variation in glycemic control in patients with type 2 diabetes mellitus during COVID-19: a 3-year-long retrospective cohort study in older adults in Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed our lifestyle by imposing restrictions, such as physical distancing. The effect of COVID-19 prevalence on seasonal variations in glycemic control in patients with diabetes mellitus (DM) remains unknown. METHODS: This single-center retrospective cohort study evaluated glycemic control in patients with type 2 DM who visited Sugi Cardiovascular Hospital in December 2021. We evaluated the clinical findings of all patients treated regularly between March 1, 2019, and December 31, 2021, including the periods both before and after the COVID-19 pandemic. All the standard treatments were approved. Furthermore, seasonal changes in hemoglobin A1c (HbA1c) levels were evaluated using stratified analyses based on age. RESULTS: This study analyzed 86 patients (mean age, 69.6 ± 9.2 years; men, 57). Median HbA1c (National Glycohemoglobin Standardization Program [Union of Clinical Chemistry]) levels in spring (March) were 7.70% (interquartile range (IQR):7.23%-8.30%) [60.6 mmol/mol (IQR:55.4-67.2 mmol/mol)], 7.35% (IQR:6.90%-7.90%) [56.8 mmol/mol (IQR:51.9-62.8 mmol/mol)], and 7.50% (IQR:7.10%-8.00%) [58.5 mmol/mol (IQR:54.1-63.9 mmol/mol)] in 2019, 2020, and 2021, respectively. During these periods, HbA1c levels and body mass index (BMI) revealed significant seasonal variations "high in spring" and "low in autumn." Median HbA1c levels in spring (March) and autumn (September) were 7.86% [61.2 mmol/mol] and 7.48% [57.4 mmol/mol] in 2019 (P < 0.001), 7.50% [57.7 mmol/mol] and 7.17% [54.2 mmol/mol] in 2020 (P < 0.001), and 7.61% [58.3 mmol/mol] and 7.19% [53.8 mmol/mol] in 2021 (P < 0.001). Seasonal variations in HbA1c levels and BMI were maintained over the past 3 years, including the pandemic period. None of the patients in this study developed COVID-19 during the study period. CONCLUSIONS: Seasonal variations in glycemic control in patients with DM were not influenced by lifestyle modifications associated with COVID-19. Maintenance of physical activity is necessary to prevent the development of sarcopenia. Moreover, seasonal variations in glycemic metabolism should be considered an independent factor for DM management. Additional extensive multifacility investigations are necessary to corroborate our findings.

Prasugrel effectively reduces the platelet reactivity units in patients with genetically metabolic dysfunction of cytochrome P450 2C19 who are treated with long-term dual antiplatelet therapy after undergoing drug-eluting stent implantation.

Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y12 inhibitors on platelet reactivity (P2Y12 reaction units: PRU), from acute to late phase after PCI. However, the effect of switching at very late phase is unknown. This study examined the effect on PRU in Japanese coronary heart disease patients with long-term DAPT (aspirin + clopidogrel) when switching from clopidogrel to prasugrel. Ninety-six patients were enrolled in this study. The median DAPT duration at enrollment was 1824.0 days. Twenty-three patients with PRU ≥ 208 at enrollment were randomly assigned into either continuing to receive clopidogrel (Continued Group; n = 11) or switching to prasugrel (Switched Group; n = 12). The primary endpoint was the rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment, which was significantly higher in Switched Group relative to Continued Group (90.0% vs. 36.4%; P = 0.024). The secondary endpoint was the PRU at week 12 in groups subdivided according to cytochrome P450 (CYP) 2C19 genotypes. At week 12, extensive metabolizers (EM Group) had 202.3 ± 60.0 and 174.5 ± 22.3 in Continued Group and Switched Group (P = 0.591), respectively; intermediate and poor metabolizers (non-EM Group) had 229.4 ± 36.9 and 148.4 ± 48.4 in Continued Group and Switched Group (P = 0.002), respectively. The PRU for non-EM Group was significantly reduced in Switched Group. Thus, for patients with long-term DAPT (aspirin + clopidogrel) after PCI with coronary stent implantation, switching from clopidogrel to prasugrel resulted in a stable reduction in PRU, regardless of CYP2C19 polymorphism.

Prolonged Inflation Technique Using a Scoring Balloon for Severe Calcified Lesion.

Percutaneous coronary intervention for the treatment of a severe calcified lesion is still one of the most technically challenging areas of interventional cardiology. Calcified lesions are a cause of stent underexpansion, which significantly increases the subsequent risks of in-stent restenosis and thrombosis, even when drug-eluting stents are used. In this report, we describe the usefulness of prolonged inflations using a scoring balloon catheter (Scoreflex) for severe calcified lesions. Prolonged inflation using a scoring balloon enables an adequate dilation for treatment of a severe calcified plaque that was unresponsive to conventional technique with or without rotational atherectomy.

[Preoperative S-1/CDDP combination chemotherapy was effective in a case of local advanced gastric cancer].

INTRODUCTION: The prognosis of type 4 advanced gastric cancer is extremely poor, even the use of multidisciplinary treatment cannot provide satisfactory results. Presented here is a case of highly advanced gastric cancer in which preoperative chemotherapy was effective and resection possible. CASE: A 64-year-old female complained of epigastric distress. Current medical history included: hypertension, hyperlipemia, diabetes, chronic heart disease and development of epigastric distress. Endoscopy was performed upon examination in the Gastroenterology Department. Visual inspection showed a lesion extending from the greater curvature of the fundus to the antrum. Type 4 advanced gastric cancer was strongly suspected. Biopsy samples taken from the antral lesser curvature and from the ulcer border on the upper anterior wall of the body were diagnosed as Group V, adenocarcinoma. Abdominal CT revealed no hepatic mass, but overall thickening of the gastric wall was noticeable and the lymph nodes in the area of the lesser curvature of the stomach and celiac artery were identified. Abdominal ultrasound showed an overall thickening of the gastric wall, and invasion into a portion of the left hepatic lobe and pancreas was suspected. Swelling of the lymph nodes surrounding the stomach was suspected. TREATMENT: Because of gastric cancer with suspected invasion of the left hepatic lobe and pancreas, it was decided to perform preoperative chemotherapy (S-1 + CDDP) and then perform a total gastrectomy. Four courses were performed. RESULTS: Endoscopy revealed no change in the lesion within the stomach. Only scarring in the body and antrum was found, the enlargement was greatly reduced and visual inspection revealed no esophageal infiltration. Biopsy samples were taken from 2 sites, the body center on the lesser curvature side and the greater curvature of the antrum. Scar-like fibrosis was significant and it was not possible to distinguish an increase in poorly differentiated adenocarcinoma. Abdominal CT showed a reduction in gastric wall thickening. These findings showed preoperative chemotherapy to be effective. Following the chemotherapy, a total gastrectomy in addition to splenectomy and cholecystectomy were performed. Histopathological findings showed MLU, type 5, approx. 8.5 × 13 cm, poorly differentiated adenocarcinoma (por 2), INF γ, sci, pT2 (SS), ly2, v0, pN2 (#1: 2/8, #6: 1/6, #11p: 2/5), pPM (-), pDM (-), Stage IIIA. Along with the formation of fibrous scar tissue, an invasive growth of por 2 poorly differentiated adenocarcinoma was found from the submucosal layer to just beneath the serosal layer. Therapeutic effect of the chemotherapy was Grade 2. Post operative S-1 + CDDP was begun but nausea developed and S-1 was reduced. Because of a decrease of neutrophils and nausea, the therapy was changed to UFT. It is currently 6 months after surgery and there are no signs of recurrence. CONCLUSION: Preoperative chemotherapy (S-1 + CDDP) is a therapy which shows promise in reducing tumor size even in highly advanced gastric cancer.

[A case in which intra-arterial chemotherapy for simultaneous hepatic metastases markedly improved AFP-producing gastric cancer].

The prognosis of most hepatic and lymph node metastases in AFP-producing gastric cancer is poor, and despite the use of multimodal therapy, the average survival period is reported to be approximately one year. Described here is one example in which intra-arterial chemotherapy for simultaneous hepatic metastases in AFP-producing gastric cancer achieved a marked improvement. The patient is a 65-year-old female. Distal gastrectomy was performed for Type II gastric cancer. L, type 2, 5.5x2.4 cm, tub 2>por 1, pT2 (MP), int, INF b, ly2, v1, pN1, pPM (-), pDM (-), pH1: stage IV. The AFP level before surgery was 801.4 ng/mL and lowered to 65.8 ng/mL after surgery, AFP-producing gastric cancer and simultaneous hepatic metastases (S4, single lesion) was diagnosed based upon imaging examinations. 5-FU+epirubicin+MMC (FEM)intra-arterial chemotherapy was started one month following surgery, but because CT showed multiple new hepatic lesions(S4, S5)four months following surgery, DSM therapy was performed with hepatic arterial injections of MMC 10 mg, DSM 300 mg. Dynamic CT showed a reduction in size of the tumors in both S4 and S5, and at five months following surgery, hepatic arterial infusion chemotherapy FP (CDDP 5 mg+5-FU 250 mg weekly) was started and performed 45 times in a 14-month period. During therapy, CR was achieved for the hepatic metastases and tumor marker levels were also normal. Because an introduction of contrast medium into the hepatic reservoir showed a narrowing of the hepatic artery and inflow of contrast medium into the splenic artery, arterial infusion was terminated. Following this, from the 20th month following surgery, S-1 (100 mg/day: 4 weeks administration, 2 weeks rest) was started and from the third course (50 mg/ day: 4 weeks administration, 2 weeks rest), and the patient is currently undergoing a sixth course. Currently, 2 years and 4 months after surgery, there have been no recurrences. This suggests the possibility that intra-arterial chemotherapy is an effective treatment method for hepatic metastases in AFP-producing gastric cancer.

Changes in P2Y12 reaction units after switching treatments from prasugrel to clopidogrel in Japanese patients with acute coronary syndrome followed by elective coronary stenting.

Patients with ischemic heart disease are administered a dual antiplatelet therapy after percutaneous coronary intervention. This consists of aspirin and thienopyridine, which can be switched from prasugrel to clopidogrel. However, the impact of switching is unknown. This study aimed to determine the efficacy and safety of switching from prasugrel to clopidogrel in Japanese patients. One-hundred and thirty-six patients with acute coronary syndrome scheduled to undergo percutaneous coronary intervention and patients with coronary artery disease requiring elective coronary stenting were enrolled. Patients were randomly assigned into the following groups: prasugrel for 6 weeks at loading/maintenance doses of 20/3.75 mg (Continued Group; n = 68) or prasugrel at 20/3.75 mg for 2 weeks followed by clopidogrel at 75 mg for 4 weeks (Switched Group; n = 68). Aspirin (loading dose/maintenance dose 324/81-100 mg/day) was coadministered in both groups. The primary endpoint was the mean P2Y12 reaction unit (PRU) at week 6 and the secondary endpoint was the PRU in groups subdivided based on the presence of CYP2C19 gene polymorphisms. At week 6, the PRU was significantly lower in the Continued Group relative to the Switched Group (140.7 and 183.0, respectively; P < 0.001), which was also evident after correction with the baseline values (144.1 vs. 176.6, respectively; P = 0.005). Extensive and poor metabolizers in the Switched Group, based on CYP2C19 gene polymorphisms, had significantly higher PRU values than those in the Continued Group. Thus, switching treatments from prasugrel to clopidogrel significantly increased the PRU in patients receiving antiplatelet therapy subsequent to percutaneous coronary intervention. Clinical Trial Registration UMIN ID, UMIN000015122.

[Two cases of inoperable gastric cancer successively treated with TS-1+CDDP as neoadjuvant chemotherapy].

CASE 1: A 30-year-old male with a loss of appetite and hematemesis was diagnosed with scirrhous gastric cancer upon detailed examination. Laparoscopic biopsy showed it to be Group V. Pre-operative diagnosis was T3N3P1HOM1, Stage V. Three courses of pre-operative chemotherapy (NAC) of TS-1+CDDP were performed. Laparoscopic examination as well as imaging showed a clear reduction in tumor size. Total gastrectomy, resection of the small intestine and cholecystectomy were performed. Pathological findings were type 4, por 2, pT3 (ss), ly1, v0, pN0, pM1 (gall bladder, small intestine): pStage IV. CASE 2: A 55-year-old male with epigastric pain was diagnosed with scirrhous gastric cancer upon detailed examination. Pre-operative diagnosis was T3N1P1H0M0, Stage IIIA. Upon surgery, gastro-jejunal anastomosis was performed as resection was not an optional. Three courses of TS-1+CDDP were performed. A clear reduction of tumor size was noted upon laparoscopic examination as well as imaging and distal gastrectomy was performed. The pathological findings shown were type 4, por 2, pT3 (ss), ly2, v1, pN1, p1, pStage IV. The prognosis for inoperable gastric cancer is not promising and there is no established treatment guideline, however, there are cases in which TS-1+CDDP therapy has made surgery possible, and with the anticipation of extended survival, can be considered a useful therapy method.

[Radiofrequency ablation (RFA) in colorectal cancer with hepatic metastases].

We considered the appropriateness of RFA, which was performed in three cases of colorectal cancer with hepatic metastases accompanied by liver cirrhosis. Case 1 involved a patient with sigmoid colon cancer ss, n1 (+) with severe hepatic dysfunction and synchronous hepatic metastases (S5, S6, S8) in which RFA was performed. After 1 year and 6 months, recurrence (S3, S4) was detected in the residual liver, and the patient is currently undergoing the IFL (CPT-11/5-FU/Leucovorin) treatment. In case 2, following a partial hepatic resection, RFA was performed for cecal cancer ss, n2(+) with synchronous hepatic metastases (S5, S6, S8). After 11 months, recurrence (S5, S6, S7) occurred in residual liver and again RFA was performed following a partial hepatic resection. Lung metastases have occurred and currently IFL (CPT-11/5-FU/Leucovorin) and WHF treatments are underway. In case 3, 4 years and 8 months after cancer of the descending colon ss, n1 (+), RFA was performed on asynchronous hepatic metastases (S5, S7, S8). The patient died of peritonitis carcinomatosa one year after RFA. In all three cases, metastases were identified by dynamic CT as low density masses with no blood flow. Necrosis in all three metastases and local control had been achieved. There were no severe complications. Under the current conditions, local coagulation methods including RFA are appropriate in those cases in which resection are not possible such as multiple metastases with severe hepatic dysfunction, etc.

Midpeliq reduces glucose load.

The rate of technique failure is still high in Japan for peritoneal dialysis (PD) patients. Of the dropouts who have been treated with PD for more than 6 years, about half suffer from ultrafiltration failure. That condition is supposedly related to the bioincompatible aspects of conventional acidic PD solutions. In 2001, a neutral-pH, lactate-buffered PD solution with low glucose degradation products (GDPs), Midpeliq (Terumo Corporation, Tokyo, Japan), was developed and began to be used in Japan. After switching 3 patients from conventional acidic PD solution to Midpeliq, we observed that 2 patients could then use lower-glucose PD solutions. Case 1 was a 42-year-old woman with a 10-year history of PD. In February 2001, she was switched from Peritoliq (Terumo) to Midpeliq. One month later, she complained of dizziness, and her blood pressure was found to be down to 96/60 mmHg. Post-change fluid removal increased to 1,481 mL from 1,238 mL (p < 0.02). Before the solution switch, this patient exchanged 4 times daily, using 2 L of 2.5% Peritoliq each time. From 3 months after the solution switch, she exchanged 3 times daily using 2 L of 2.5% Midpeliq and 1 time daily using 2 L of 1.35% Midpeliq. Fluid volume removal stayed almost the same. Case 2 was a 52-year-old man with a 9-year history of PD. In June 2002, he was switched from Dianeal 4 (Baxter Healthcare, Tokyo, Japan) to Midpeliq. After the change, his daily drainage volume increased from approximately 1,500 mL to 2,000 mL. He began to use 2 L of 1.35% Midpeliq 4 times daily instead of 2 L of 1.5% Dianeal 3 times daily and 2 L of 2.5% Dianeal 1 time daily. At 1 month after the solution switch, his drainage volume was still approximately 1,500 mL daily. Our observations suggest that new, neutral-pH PD solutions such as Midpeliq might reduce the glucose load in addition to having low GDPs and fewer toxic effects on the peritoneum.

[The use of radio frequency ablation (RFA) for colorectal liver metastases in one patient].

We studied one case in which the application of RFA was used for colorectal liver metastases with cirrhosis. The patient was a 51-year-old male. Sigmoid colon cancer and hepatocellular cancer (S5, S6, S8) were diagnosed before surgery. RFA was planned, as resection was determined to be impossible, because of reduced reserve liver function due to hepatitis B and cirrhosis. Resection of the Sigmoid colon was performed. Rapid pathological diagnosis was performed on the liver tumor and it was determined to be metastases from the sigmoid colon cancer. RFA was performed on the liver tumor with the expectation of local control. After the operation, WHF arterial infusion was performed as an outpatient, but the blood platelet count decreased and that resulted in impaired liver function making the continuation of WHF arterial infusion at a regular pace difficult. After 11 months from the operation, multiple recurrences appeared and the infusion was restarted. Consequently, the tumor size was reduced. Following the infusion, however, the liver function became impaired and there was no choice but to discontinue the infusion. After one year and 9 months from the operation, multiple recurrences appeared in the residual liver and WHF arterial infusion was restarted. The tumor size gradually reduced after the infusion and only S3 currently remains with good local control. Because this example was a case with multiple metastases along with a high level of liver function impairment, RFA was tested and good local control was achieved. In cases such as these where liver resection is not possible, local ablation therapies including RFA are applicable.

[Evaluation of intraarterial infusion chemotherapy for liver metastasis from gastric cancer FEM: combination therapy of 5-FU, epirubicin and MMC].

OBJECTIVE: We evaluated the effectiveness of FEM (5-FU, epirubicin, MMC) therapy. SUBJECTS: Data for 111 patients with liver metastasis from gastric cancer were collected from January 1977, until June 2003 (synchronous: 74 cases, asynchronous: 37 cases). Thirty patients were H1, 20 were H2 and 61 were classified as H3. METHODS: The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 10), Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intraarterial infusion (5 cases). Group B: Resection of the primary lesion (n = 67), Group B1: Resection of the primary lesion only (46 cases), Group B2: Intraarterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (4 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. RESULTS: 1-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%. 4.8 months; and Group C: 6%, 3.9 months, respectively. One case from Group A2a and 2 cases from Group B2a have survived for 3 years or longer. CONCLUSION: 1) We treated 3 patients with liver metastasis from gastric cancer who survived for 3 years or longer. 2) Resection of the primary lesion along with hepatic intraarterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended length of survival.

[Evaluation of intra-arterial infusion chemotherapy for liver metastasis from gastric cancer FEM--combination therapy of 5 FU, Epirubicin and MMC].

OBJECTIVE: We evaluated the effectiveness of FEM (5-FU, Epirubicin, MMC) therapy. SUBJECTS: One hundred ten cases of liver metastasis from gastric cancer were collected from January, 1977 until June, 2001 (synchronous: 74 cases, asynchronous: 36 cases). Twenty-nine cases were H1, 20 cases were H2 and 61 cases were H3. METHODS: The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 9); Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intra-arterial infusion (4 cases). Group B: Resection of the primary lesion (n = 67); Group B1: Resection of the primary lesion only (46 cases), Group B2: Intra-arterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (3 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. RESULTS: One-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%, 4.8 months; and Group C: 6%, 3.9 months, respectively. Five patients from Groups A2a and B2a survived for one year or longer. CONCLUSION: 1. The prognosis with liver metastasis from gastric cancer, even with a number of therapies, is not promising. 2. Resection of the primary lesion along with hepatic intra-arterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended survival.

[Resection made possible following hepatic arterial infusion in 2 cases of hepatic metastases from colorectal cancer].

Of 66 examples of hepatic metastases from colorectal cancer, 30 cases in which resection was performed had 3- and 5-year cumulative survival rates of 66.7% and 56.8%, while in 36 cases in which resection was not possible, the percentages were 8.7% and 2.9%, respectively. In two of the latter cases, resection was possible following WHF (5-FU 1,000 mg/m2 5 h qw). Case 1: A 58-year-old male, with rectal cancer and multiple metastases (H3, synchronous). Arterial infusion was performed 21 times, with the total volume of 5-FU administered being 31.5 g. The size of the lesions was reduced and hepatic resection was performed. The patient later died due to local recurrence and intra-abdominal lymph node metastases. He had survived 2 years and 11 months following hepatic resection and was free from recurrence of hepatic metastases. Case 2: An 82-year-old female, with cancer of the ascending colon, sigmoidal colon and multiple hepatic metastases (H3, metachronous). Arterial infusion was performed 16 times, with the total amount of 5-FU administered being 20 g. A lowering of CEA levels and reduction of tumor size were achieved, and hepatic resection was performed. Seven months following hepatic resection, CEA levels are normal and no distant metastases or recurrence in the residual liver have been found: possibly a complete cure. Even among cases of unresectable hepatic metastases from colorectal cancer, there are some in which resection is possible following hepatic arterial infusion chemotherapy, with the possibility of complete cure.

Early outgrowth EPCs generation is reduced in patients with Buerger's disease.

BACKGROUND: Buerger's disease often shows poor collateral artery generation (i.e. neovascularization) in the ischemic limbs. However, the etiology has not yet been clarified. Circulating endothelial progenitor cells (EPCs) derived from bone marrow contribute to neovascularization in the multi-step process which includes the following capacities; mobilization, differentiation, adhesion, migration, invasion and secretion. MATERIALS AND METHODS: We assessed EPCs capacities in vitro and ex vivo in age- and sex-matched controls (n = 12) and patients with Buerger's disease (n = 12), derived from peripheral blood-derived mononuclear cells (PB-MNCs). RESULTS: In the flow cytometry analysis, the numbers of circulating EPC (CD34(+)/KDR(+) or CD133(+)/KDR(+) PB-MNC) were similar between controls and patients with Buerger's disease. Next, we cultured PB-MNC to obtain EPCs. The number of early outgrowth EPCs was significantly decreased in patients with Buerger's disease (p < 0.005), indicating the reduced generation of early outgrowth EPCs in Buerger's disease. However, adhesion, migration, invasion and secretion capacities were not impaired in patients with Buerger's disease. CONCLUSIONS: The early outgrowth EPCs generation is reduced in patients with Buerger's disease.

Vitamin C reversed malfunction of peripheral blood-derived mononuclear cells in smokers through antioxidant properties.

BACKGROUND: Smoking impairs neovascularization, possibly, through the impaired function of peripheral blood-derived mononuclear cells (PB-MNCs). Thus, the mechanism of impaired function of PB-MNCs caused by chronic smoking was examined, and whether vitamin C reversed the malfunction of PB-MNCs in smokers was investigated. METHODS AND RESULTS: The cohort comprised 27 healthy male volunteers (16 smokers and 11 age-matched non-smokers). For evaluation of the colony-forming activity of PB-MNCs, the number of endothelial colony-forming units (e-CFUs) was counted in a culture assay. Migration activity of PB-MNCs was evaluated by the modified Boyden chamber method. In smokers, the number of e-CFUs was reduced to 56% and migratory activity of PB-MNCs to 40% compared with non-smokers (p<0.01). The urinary level of 8-isoprostane, an oxidative stress marker, was greater in smokers than in non-smokers (p<0.05). There was an inverse correlation between migratory activity of PB-MNCs but not between the number of e-CFUs and urinary level of 8-isoprostane. Furthermore, oral administration of vitamin C for 2 weeks ameliorated the impaired migratory activity of PB-MNCs in smokers. CONCLUSION: Chronic smoking impairs the function of PB-MNCs. Smoking-induced oxidative stress may be involved in impaired migratory activity of PB-MNCs.

Pigment epithelium-derived factor (PEDF) administration inhibits occlusive thrombus formation in rats: a possible participation of reduced intraplatelet PEDF in thrombosis of acute coronary syndromes.

OBJECTIVES: Although remarkable therapeutic advances in the treatment of acute coronary syndromes (ACS) have been made with anti-platelet therapy, the therapeutic options may be limited by considerable side effects. Pigment epithelium-derived factor (PEDF) has anti-oxidative properties and may play a protective role against atherosclerosis. In this study, we investigated whether PEDF prevented occlusive thrombus formation in rats. METHODS AND RESULTS: Occlusive thrombus formation was induced by treating rats with ligation and cuff placement at the left common carotid artery. Intravenous injection of PEDF dose-dependently inhibited thrombus formation and blocked the increase in immunoreactivity of P-selectin, a marker of platelet activation, NADPH oxidase activity and superoxide generation in thrombi. In vitro, PEDF significantly decreased collagen-induced reactive oxygen species generation in platelets and subsequently suppressed the platelet activation and aggregation. Plasma and intraplatelet levels of PEDF in the coronary circulation in patients with ACS were significantly lower than those in age- and gender-matched controls without coronary artery disease. CONCLUSIONS: These results demonstrated that PEDF administration could inhibit occlusive thrombus formation by blocking the platelet activation and aggregation through its anti-oxidative properties. Our present study suggests that pharmacological up-regulation or substitution of PEDF may offer a promising strategy for the treatment of arterial thrombosis.

Effect of autologous bone-marrow cell transplantation on ischemic ulcer in patients with Buerger's disease.

BACKGROUND: Thromboangiitis obliterans, also known as Buerger's disease, is characterized by peripheral occlusive changes in the arteries of the upper and lower limbs and treatment is often ineffective. Intramuscular transplantation of autologous bone marrow-mononuclear cells (BM-MNC) has been recently reported as improving the symptoms and clinical manifestations in patients with severely ischemic limbs, mostly caused by arteriosclerosis obliterans. The present study focused on the patients with Buerger's disease presenting with rest pain and/or skin ulcer uncontrolled by conventional treatments. METHODS AND RESULTS: Fourteen patients with Buerger's disease (Fontaine III: n=2, Fontaine IV: n=12) underwent transplantation of autologous BM-MNC into ischemic skeletal muscles of either the upper or lower limb. After 4 weeks, rest pain was significantly reduced. In 19 skin ulcers of 9 patients, 8 ulcers were healed and 8 were diminished in the size. These improvements were maintained for 24 weeks without complications. CONCLUSIONS: In patients with Buerger's disease, intramuscular transplantation of autologous BM-MNC improved symptoms and clinical manifestations, especially skin ulcer.

Management of refractory ascites by using a peritoneal dialysis system with extracorporeal ultrafiltration by hemodialysis dialyzer.

BACKGROUND: The treatment of refractory ascites remains a challenge in cirrhosis with ascites and end-stage renal disease (ESRD). Successful experiences with continuous ambulatory peritoneal dialysis (CAPD) for treatment of ESRD patients with ascites secondary to liver cirrhosis have been reported, but the CAPD modality has the drawback of protein loss and was observed to cause patients to become severely malnourished. We devised a CAPD method for treatment of ascites without protein loss. We use a peritoneal dialysis (PD) system to drain ascitic fluid and to reinject concentrated ascites into the abdomen after extracorporeal ultrafiltration of the ascitic fluid using a hemodialysis dialyzer and pump. Here, we report our experience with 2 cirrhotic patients with ascites treated by this method. PATIENTS AND METHOD: Ascites are collected by gravity through a Y transfer set into a 3-L plastic bag for intravenous hyperalimentation. The ascitic fluid drained is removed by a pump at a rate of 200 mL/min (AK-90: Gambro Lundia, Lund, Sweden) and passed through a hollow-fiber dialyzer with triacetate membrane (FB-210G: Nipro, Osaka, Japan). Heparin (5,000 U) is infused into the inflow line at the start of the session only. At the end of treatment, about 500 mL concentrated ascitic fluid is returned to the peritoneal cavity by gravity through the Y transfer set. Case 1: A 77-year-old female was referred to us because of massive ascites from hepatic cirrhosis associated with hepatitis B infection and renal insufficiency. Abdominal paracentesis was required once weekly for recurrence of massive ascites. As a result, the patient was obliged to stay in the bed almost all day, and her nutritional condition deteriorated because of poor appetite and respiratory compromise. Using the Y transfer set, we commenced using our method, and performed it thrice or twice weekly. After 9 months of treatment, the patient's body weight was being maintained at 52 kg, and her serum albumin level had risen from 2.4 g/dL to 3.4 g/dL without albumin administration. Case 2: A 61-year-old male with diabetes from the age of 51 was diagnosed with hepatitis C at age 53. At age 60, his renal function deteriorated, requiring hemodialysis (HD). After 3 months, abdominal distention was noted, and HD was frequently complicated by low blood pressure, large weight gains between HD treatments, and interruption of HD sessions. Albumin administration was required to treat the low blood pressure. Ascites was poorly controlled using HD, and tense ascites developed, requiring repeated paracentesis for comfort. At first during application of our method, ascitic fluid volume was 6 L per thrice-weekly HD session. After 5 months, ascitic fluid volume had diminished to about 2 - 3 L per HD session, and we decreased the frequency of our method to once weekly. Protein levels in the ascitic fluid were 6 g/dL at the start of treatment and decreased to 2 - 3 g/dL after 6 months. Hemodynamic instability during HD was reduced. CONCLUSION: We conclude that management of refractory ascites by using a PD system with extracorporeal ultrafiltration by an HD dialyzer is useful. The technique compensates for the drawbacks of PD management of ESRD patients with ascites, although further experience with the technique is necessary.