Levofloxacin-azithromycin combined triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of levofloxacin- azithromycin combined triple therapy for H. pylori eradication. METHODS: 1) First-line eradication: A total of 78 H. pylori-positive patients were enrolled. Seventeen military men in Armed Forces Capital Hospital were treated with 7 days of levofloxacin-azithromycin combined triple therapy (omeprazole 20 mg bid, levofloxacin 500 mg od, and azithromycin 500 mg od), and 61 patients in Kangbuk Samsung Hospital were treated with standard PPI-based triple therapy (omeprazole 20 mg bid, amoxicillin 1.0 g bid, and clarithromycin 500 mg bid) for 7 days. 2) Second-line eradication: A consecutive series of 59 patients who failed H. pylori eradication with standard PPI-based triple therapy in Kangbuk Samsung Hospital were randomized to two groups. Thirty patients were retreated with 7 days of bismuth-based quadruple therapy (omeprazole 20 mg bid, bismuth 120 mg qid, metronidazole 500 mg tid, and tetracycline 500 mg qid), and remaining 29 patients were retreated with levofloxacin-azithromycin combined triple therapy. Patient's compliance and tolerability were evaluated at the end of treatment. The status of H. pylori infection was assessed 8 weeks later then. The successful eradication of H. pylori was defined as negative results from histology and CLO test, or 13C-urea breath test. RESULTS: First-line eradication rate of levofloxacin-azithromycin triple therapy was lower than that of standard PPI-based triple therapy, but there was no statistically significant difference (70.6% vs. 80.3%, p=0.390). Second-line eradication rate of levofloxacin-azithromycin combined triple therapy was significantly lower than that of bismuth-based quadruple therapy (ITT/PP 65.5%/73.1% vs. 90%/90%, p<0.0001). The compliances of all patients were more than 85%. Two of patients with levofloxacin-azithromycin combined triple therapy complained self-limiting side effects (mild dizziness; mild insomnia with general weakness). CONCLUSIONS: Levofloxacin-azithromycin combined triple therapy should not be recommended as the first-line or second-line H. pylori eradication regimen in Korea.     

Is gastric cancer a new indication for surveillance colonoscopy? Colon cancer is increased in gastric cancer patients]

BACKGROUND/AIMS: It has been reported that the risk of gastric polyp is increased in various colonic polyposis syndromes or in series of patients with sporadic colonic polyps. However, there are only a few large case controlled studies of colon cancer incidence in gastric cancer patients who underwent colonoscopy. The aims of this study were to determine the incidence of colorectal neoplasm and to evaluate the necessity of colonoscopic surveillance in patients with gastric cancer. METHODS: We performed colonoscopy in 105 patients with gastric cancer who agreed to undergo colonoscopy before or after 6 months from gastric resection between January 2002 and December 2004 in Kangbuk Samsung hospital. As a control group, 269 consecutive, age and sex matched patients without gastric neoplasm on gastroscopy who underwent colonoscopy within 6 months for the evaluation of various gastrointestinal symptoms during the year 2004 were included. Endoscopic reports and pathological results were reviewed retrospectively. RESULTS: In the patient group, adenomatous polyps were diagnosed in 24/105 patients (22.9%) and colorectal adenocarcinoma in 10/105 patients (9.5%). In the control group, adenomatous polyps were diagnosed in 78/269 patients (29.0%) and colorectal adenocarcinoma in 2/269 patients (0.7%). The incidence of colorectal adenocarcinoma between the patient group and control group showed significant differences (odds ratio 11.04, p=0.003). CONCLUSIONS: The risk of colorectal adenocarcinoma increases significantly in patients with gastric cancer. We suggest that the patients with gastric cancer might carry a high risk for colorectal cancer whom require surveillance colonoscopy.     

Comparison of treatment strategies for patients with intestinal diffuse large B-cell lymphoma: surgical resection followed by chemotherapy versus chemotherapy alone

The aim of this retrospective cohort study was to analyze the impact of surgery on the outcomes and qualities of life (QOL) in patients with intestinal diffuse large B-cell lymphoma (DLBCL). We assessed 345 patients with either localized or disseminated intestinal DLBCL and compared them according to treatment: surgical resection followed by chemotherapy versus chemotherapy alone. In patients with localized disease (Lugano stage I/II), surgery plus chemotherapy yielded a lower relapse rate (15.3%) than did chemotherapy alone (36.8%, P < .001). The 3-year overall survival rate was 91% in the surgery plus chemotherapy group and 62% in the chemotherapy-alone group (P < .001). The predominant pattern in the chemotherapy group was local relapse (27.6%). When rituximab was used with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), there was no improvement of the outcomes in patients treated with primary surgical resection. The QOL of patients who underwent surgery and chemotherapy was lower than chemotherapy alone, but its difference was acceptable. Multivariate analysis showed that surgical resection plus chemotherapy was an independent prognostic factor for overall survival. Surgical resection followed by chemotherapy might be an effective treatment strategy with acceptable QOL deterioration for localized intestinal DLBCL. This study was registered at www.clinicaltrials.gov as #NCT01043302.     

Can we identify vulnerable patients at risk for ST-segment elevation myocardial infarction based on their clinical characteristics?

OBJECTIVE: Coronary artery plaque rupture is a sudden, unpredictable event leading to acute coronary syndrome. Thus far, there is no clinical characteristic to distinguish the patients at risk for acute myocardial infarction from those with more stable coronary artery disease. The purpose of this study was to identify clinical predictors of first ST-segment elevation myocardial infarction (STEMI). METHODS: We retrospectively compared 116 consecutive patients presenting with their first STEMI for primary angioplasty and 216 ambulatory patients with stable angina requiring their first coronary intervention. RESULTS: Patients with STEMI were younger, more likely to be smokers, but less likely to have hypertension or hypercholesterolemia. Diabetes was present equally between the two groups. Cardioprotective medication usage, such as aspirin and statin, was much lower among patients presenting with their first STEMI. CONCLUSIONS: Thus, patients with STEMI presumably from plaque rupture have fewer traditional risk factors compared with patients with stable angina. Identifying these vulnerable patients at risk for plaque rupture may enable early institution of cardioprotective pharmacotherapy to prevent their first acute coronary syndrome occurrence.     

Platelet-derived growth factor improves cardiac function in a rodent myocardial infarction model

OBJECTIVES: The translation of cardioprotective therapies for myocardial infarction requires a preclinical demonstration of improved cardiovascular function following acute coronary occlusion. We previously showed that pretreatment of rodent hearts with platelet-derived growth factor (PDGF) promotes angiogenesis and decreases the extent of myocardial injury measured by histology. The present study aimed to determine the correlation of these histological findings with noninvasive measures of improvement in cardiac function. METHODS: Rats were treated with intramyocardial injections of PDGF (100 ng) or phosphate buffer solution (PBS) (n = 6 per group) 24 h prior to acute, permanent ligation of the left anterior descending artery and the extent of myocardial injury was assessed by Masson's trichrome staining 14 days later. To assess the physiological effects of PDGF pretreatment after coronary occlusion, cardiac function was assessed noninvasively by electrocardiography, exercise testing and echocardiography and correlated with direct histological measures. RESULTS: Physiological studies demonstrated that PDGF resulted in lower ST-segment elevation at the time of coronary occlusion (0.12 +/- 0.02 mV above baseline) than in PBS control rats (0.35 +/- 0.05 mV; P < 0.05). Exercise testing 14 days after coronary occlusion revealed that PDGF pretreatment resulted in faster maximal exercise speeds (28.54 +/- 3.98 m/min) than in control rats (24.98 +/- 3.13 m/min; P < 0.05). Echocardiography also revealed that the left ventricular factional shortening in the PDGF-pretreated rats was significantly greater (18.47 +/- 12.21%) than in control animals (4.91 +/- 7.21%; P<0.05). CONCLUSIONS: These studies demonstrate that PDGF pretreatment improves cardiac function following acute coronary occlusion. Strategies based on the cardioprotective actions of PDGF may provide a significant advance in the treatment of myocardial infarction.     

Safety of single versus multi-vessel angioplasty for patients with acute myocardial infarction and multi-vessel coronary artery disease: report from the New York State Angioplasty Registry

BACKGROUND: The conventional strategy for primary angioplasty during acute myocardial infarction is angioplasty of the infarct-related vessel, even in patients with multi-vessel disease. Patients, however, often have significant lesions in multiple coronary arteries and a strategy for multi-vessel angioplasty during acute myocardial infarction has not been explored. The purpose of this study was to examine whether multi-vessel angioplasty is as safe as infarct-related vessel angioplasty in patients with multi-vessel coronary artery disease during acute myocardial infarction. METHODS: Using the 2000-2001 New York State Angioplasty Registry database, we compared the in-hospital clinical outcomes of patients with multi-vessel disease (>70% stenosis in at least two major coronary arteries), who underwent either multi-vessel angioplasty (n=632) or infarct-related vessel angioplasty (n=1350) within 24 h of acute myocardial infarction. Patients with previous myocardial infarction, angioplasty, bypass surgery, or cardiogenic shock were excluded. RESULTS: Patients in the multi-vessel angioplasty group were less likely to be female, to have peripheral vascular disease or diabetes. They had more complex lesions and were more likely to receive stents. In-hospital mortality was three-fold lower (0.8 versus 2.3%, P=0.018) in the multi-vessel angioplasty group. No differences were observed in other ischemic complications, renal failure, or length of stay. After multivariate analysis, multi-vessel angioplasty remained a significant predictor of lower in-hospital death (odds ratio=0.27, 95% confidence interval=0.08-0.90, P=0.03). CONCLUSIONS: Despite the added complexity of multi-vessel angioplasty, patients in this group had significantly lower in-hospital mortality. Therefore, a strategy of multi-vessel angioplasty during acute myocardial infarction may be safe compared with infarct-related angioplasty in selected patients.     

A functional chaperone triad on the yeast ribosome

The chaperones RAC (ribosome-associated complex), consisting of Ssz1p and zuotin, and Ssb1/2p are associated with ribosomes of yeast. Ssb1/2p was previously shown to form a crosslink product to polypeptides trapped in ribosome-nascent chain complexes (RNCs) in vitro. Here we show that an efficient crosslink of the nascent chain to Ssb1/2p depends on the presence of functional RAC. The crosslink to Ssb1/2p was significantly diminished if (i) RAC was removed from RNCs: a process reversed by addition of purified RAC; (ii) RAC carried a mutation in the J-domain of zuotin, leading to its inactivation in vivo; (iii) RAC's Ssz1p subunit was absent because RNCs were generated in a Deltassz1-derived translation extract. In vivo the same specific set of growth defects caused by the absence of any of the three chaperones was also displayed by a Deltassb1/2Deltassz1Deltazuo1 strain. The combination of in vitro and in vivo data supports a model in which Ssb1/2p, Ssz1p, and zuotin act in concert on nascent chains while they are being synthesized.     

Induction of neutralizing antibodies and partial protection from viral challenge in Macaca fascicularis immunized with recombinant dengue 4 virus envelope glycoprotein expressed in Pichia pastoris

A recombinant vaccine that expresses the envelope (E) gene of dengue virus type 4 was tested for immunogenicity and protection in Macaca fascicularis. One hundred micrograms of semipurified recombinant E protein (E4rec) expressed in Pichia pastoris was used to immunize three animals. Neutralizing antibodies to dengue 4 virus with a titer of 1:30 were detected in all immunized monkeys prior to challenge. Animals were challenged with 10(5) plaque-forming units of dengue 4 virus. One vaccine-immunized monkey was protected from viremia, while the other two were partially protected. Monkeys immunized with E4rec elicited the highest neutralizing antibody titers (P < 0.05) ranging from 1:85 to 1:640 at day 30. In both immunized and control animals, the longest duration of viremia correlated with earliest and highest level of IgM antibody to dengue virus. The vaccinated animals showed anamnestic antibody responses upon virus challenge, indicating successful priming by the recombinant vaccine. Our results suggest that E4rec expressed in P. pastoris can provide partial protection against viremia. However, the results were not effective enough to use it as a vaccine candidate. Further work is required to improve the quality of the immunogen.     

Right trisegmentectomy with thoracoabdominal approach after transarterial embolization for giant hepatic hemangioma

Hepatic hemangiomas need to be treated surgically in cases where they are accompanied with symptoms, have a risk of rupture, or are hardly distinguishable from malignancy. The present authors conducted embolization of the right hepatic artery one day before an operation for a huge hemangioma accompanied with symptoms and confirmed a decrease in its size. The authors performed a right trisegmentectomy through a J-shape incision, using a thoracoabdominal approach, and safely removed a giant hemangioma of 32.0 cm × 26.5 cm× 8.0 cm in size and 2300 g in weight. Even for inexperienced surgeons, a J-shape incision with a thoracoabdominal approach is considered a safe and useful method when right-side hepatectomy is required for a large mass in the right liver.     

CD34, RAB20, PU.1 and GFI1 mRNA expression in myelodysplastic syndrome

Myelodysplastic syndrome (MDS) with hypocellular bone marrow (BM) is often difficult to distinguish from aplastic anemia (AA). Furthermore, the diagnosis of MDS with low blast counts and normal karyotype may be problematic. These issues highlight the need for a reliable marker for the diagnosis of MDS. This study was conducted to determine if changes of mRNA expression in any of the four selected genes would be useful markers for differentiation of hypoplastic MDS from AA, and MDS from benign disease, as well as to investigate whether mRNA expressions differ between MDS risk subgroups. Thirty-five patients diagnosed with MDS, 27 patients with AA and 17 patients with benign diseases were included. The CD34, RAB20, PU.1 and GFI1 mRNA levels were measured by real-time RT-PCR. The CD34 mRNA expressions in hypoplastic MDS were higher than those found in AA. PU.1 and GFI1 mRNA expressions were significantly lower in MDS with low blast counts and normal karyotype than those of benign disease. High-risk MDS showed higher CD34 expressions than those of low-risk MDS. This study suggests that measurement of CD34 and GFI1 mRNA expressions could be useful as a diagnostic and prognostic marker for MDS.