BACKGROUND: Previous antibiotic exposure may inhibit the growth of microorganisms in blood culture bottles. The authors investigated the frequency of previous antibiotic usage and analyzed the relationships among antibiotic usage, microbiological culture results and mortality of sepsis patients. METHODS: From April to May 2011, all blood cultures requested from inpatients were analyzed according to the admitted ward and antibiotic prescription records. The BacT/Alert 3D system (bioMerieux Inc.) was used with a standard bottle (SA, SN) for blood culture. RESULTS: Of 900 inpatients, 48% had been receiving antimicrobial agents when blood cultures were ordered. This group had a significantly higher mortality rate (36.2%) compared to the patients who had not received antibiotics (11.1%). Gram-negative rod bacteremia (37.1%) and candidemia (100%) resulted in a significantly higher mortality rate compared to Gram-positive cocci bacteremia (16.4%). In the analysis of 21 cases resulting in death, 15 (71.4%) patients died before or on the date when blood culture results were reported. CONCLUSION: Patients who receive antibiotics prior to blood collection may be at a higher risk for mortality. In the present study, Gram-negative rod bacteremia and candidemia cases showed a rapid progression of sepsis as indicated by Gram staining and thus should be regarded seriously.
Anti-Bacterial Agents ; Anti-Infective Agents ; Bacteremia ; Candidemia ; Gram-Positive Cocci ; Humans ; Inpatients ; Prescriptions ; Sepsis ; Sydnones

BACKGROUND AND OBJECTIVES: The stimulus signals delivered in cochlear implant (CI) systems are generally derived by sampling the temporal envelope of each channel at some constant rate and using its intensity to control the stimulation current level delivered to the corresponding electrode site. The objective of the study was to investigate speech recognition performance of cochlear implant users in quiet and noisy environments using either moderate or high rates of electrical stimulations. MATERIALS AND METHODS: Six post-lingually deafened adult users of the Nucleus CI24 cochlear implant (Contour(R) electrode array, Cochlear(TM), Macquarie Park, Australia) with the Freedom(R) speech processor participated in the study. Stimulation rates of 900 and 2400 pulses-per-second/channel (pps/ch) were used after both stimulation programs were balanced for loudness. Monosyllabic word and sentence recognition scores in quiet and noisy environments were evaluated for each stimulation program after two months of practice. Subjects were also asked to respond to a questionnaire to examine their preference to any stimulation rate in different hearing conditions. RESULTS: Word recognition scores for monosyllabic words in quiet conditions with the 900 stimulation rate was better than that of the 2400 stimulation rate, although no significant differences between them were found for sentence test in noise. A survey questionnaire indicated that most subjects preferred the 900 stimulation rate to the 2400 stimulation rate, especially in quiet conditions. CONCLUSIONS: Most subjects indicated a preference for 900 pps/ch rate in quiet conditions. It is recommended to remap at 900 pps/ch for those CI users whose performance in quiet conditions is less than ideal.
Adult ; Cochlear Implants ; Correction of Hearing Impairment ; Electric Stimulation ; Electrodes ; Hearing ; Humans ; Noise ; Speech Perception ; Sydnones ; Surveys and Questionnaires

PURPOSE: The status of axillary lymph node (LN) metastasis is the most important prognostic factor in breast cancer. Postoperative regional nodal radiotherapy is recommended usually based on the number of metastatic LNs, which is associated with the total number of removed LNs during the axillary dissection. We evaluated the prognostic impact of the ratio of metastatic LNs to removed LNs on disease free survival and overall survival in breast cancer patients. METHODS: The medical records of 743 breast cancer patients with metastatic axillary LNs and treated at Samsung Medical Center between 1994 and 2003 were retrospectively analyzed. The ratio of metastatic/removed LNs as well as the other prognostic factors were analyzed. RESULTS: Both disease-free survival and overall survival rates were significantly worse in patients with a ratio of metastatic/removed LNs greater than 20% compared to those patients with a ratio of less than 20% (p=0.028, p<0.001, respectively). In patients with T1-2 and N1 breast cancer, the ratio of metastatic/removed LNs greater than 20% was significantly associated with poorer disease-free survival (p=0.027). CONCLUSION: A ratio of metastatic/removed LNs greater than 20% in the axilla can be an adverse prognostic factor in breast cancer patients with axillary node metastasis. In T1-2 N1 breast cancer patients, adjuvant radiotherapy as well as more aggressive chemotherapy therapy may be indicated.
Axilla ; Breast ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Survival Rate ; Sydnones

PURPOSE: Postoperative pancreatic fistula is a dreadful complication after gastric cancer surgery. The purpose of this study is to evaluate the actual incidence and risk factors of postoperative pancreatic fistula after curative gastrectomy for gastric cancer. MATERIALS AND METHODS: A total of 900 patients who underwent gastrectomy for gastric cancer (laparoscopic gastrectomy, 594 patients; open gastrectomy 306 patients) were enrolled between January 2009 and December 2010. Clinical outcomes, including postoperative pancreatic fistula grade based on the International Study Group on Pancreatic Fistula, were investigated. RESULTS: Overall, the postoperative pancreatic fistula rate was 3.3% (30/900) (1.5% in laparoscopic gastrectomy versus 6.9% in open gastrectomy, P<0.001). Patients who underwent D2 lymphadenectomy, total gastrectomy, splenectomy or distal pancreatectomy showed higher postoperative pancreatic fistula rates (4.7%, 13.8%, 13.6%, or 57.1%, respectively, P<0.001). Patients with postoperative pancreatic fistula had higher morbidity (46.7% versus 13.1%, P<0.001), delayed gas out (4.9 days versus 3.8 days, P<0.001), belated diet start (5.8 days versus 3.5 days, P<0.001) and longer postoperative hospital stay (13.7 days versus 6.8 days, P<0.001). On the multivariate analysis, total gastrectomy (odds ratio 9.751, 95% confidence interval: 3.348 to 28.397, P<0.001), distal pancreatectomy (odds ratio 7.637, 95% confidence interval: 1.668 to 34.961, P=0.009) and open gastrectomy (odds ratio 2.934, 95% confidence interval: 1.100 to 7.826, P=0.032) were the independent risk factors of postoperative pancreatic fistula. CONCLUSIONS: Laparoscopic gastrectomy had an advantage over open gastrectomy in terms of the lower postoperative pancreatic fistula rate. Total gastrectomy and combined resection, such as distal pancreatectomy, should be performed carefully to minimize postoperative pancreatic fistula in gastric cancer surgery.
Diet ; Gastrectomy ; Humans ; Imidazoles ; Incidence ; Length of Stay ; Lymph Node Excision ; Multivariate Analysis ; Nitro Compounds ; Pancreatectomy ; Pancreatic Fistula ; Risk Factors ; Splenectomy ; Stomach Neoplasms ; Sydnones

We report three patients with pulmonary hypertension in Takayasu's arteritis, who showed long-term favorable response, clinically and hemodynamically, to the nitric oxide donor, molsidomine. In these patients, the inhaled nitric oxide was effective in reducing pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) as was shown in the acute vasodilator response test using the invasive hemodynamic monitoring. Molsidomine (single oral dose of 4 mg) was also effective in reducing PAP and PVR in the acute test, but nifedipine was not. With 4 mg of molsidomine three times daily, their dyspnea, exercise capacity and hemodynamic parameters were improved. These favorable responses have lasted during the 1st and 3rd month follow-up in all patients.
Dyspnea ; Follow-Up Studies ; Hemodynamics ; Humans ; Hypertension, Pulmonary* ; Molsidomine* ; Nifedipine ; Nitric Oxide* ; Pulmonary Artery ; Takayasu Arteritis* ; Tissue Donors ; Vascular Resistance

AIMTo investigate the effects of exogenous NO donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1) on automaticity of the rabbit sino-atrial node in vitro and the action mechanism.

METHODSThe intracellular microelectrode technique is used to record the action potentials of rabbit sino-atrial node and APA (amplitude of AP), V(max) (maximal rate of depolarization), VDD (velocity of diastolic depolarization), RPF (rate of pacemaker firing) are analyzed.

RESULTSSNP(10(-5) - 10(-2) mol/L) increased its RPF and VDD dose-dependently. 10(-3) mol/L SNP increased RPF (beats/min) from 163 +/- 10.8 to 195.0 +/- 13.1 increased VDD (mV/s) from 50.3 +/- 9.6 to 70.2 +/- 12.1 (P < 0.01). SIN-1(10(-3) - 10(-2) mol/L) also increased RPF and VDD (P < 0.01).10(-4) mo/L Methylene blue (MB), a blocker of GMP cyclase, prevented the positive chronotropic effect and increasement of VDD induced by 10(-3) mol/L SNP totally (P < 0.01). 2. CsCl (2 mmol/L), a blocker of I(f) prevented the increasement of RPF and VDD in part (P < 0.05). 3. NIF (0.46 micromol/L), a blocker of I(Ca-L, had no significant effects on chronotropic effect and increasement of VDD (P < 0.01).

CONCLUSIONExogenous NO can increase the automaticity of rabbit sino-atrial node in vitro. The chronotropic effect is involved in NO-cGMP pathway and results from increasement of I(f) in the sino-atrial node at least in part; I(ca-L) is unlikely to play a major role in this effect.

Action Potentials ; Animals ; Heart Rate ; Molsidomine ; analogs & derivatives ; pharmacology ; Nitric Oxide ; metabolism ; Nitroprusside ; pharmacology ; Rabbits ; Sinoatrial Node ; drug effects ; physiology

Apolipoprotein (apo) E deficient mouse can produce reproducible fixed stenotic primary atherosclerotic lesion, which reveals failure to remodel of vascular lumen, in the ascending aorta, external carotid, common carotid, iliac, femoral and popliteal arteries. To evaluate the effect of drugs in regarding to both prevention of primary atherosclerotic lesion and vascular remodeling, a systematic analysis of distribution of atherosclerotic lesions was undertaken in chow-fed, 9-momth-old apo E deficient mice, which was administrated drugs including asprin, methotrexate, probucol, sulodexide, diltiazem, cilazapril, trimetazidine, molsidomine, pentoxiphylline and Ginexin (R) for 7 month from 3 month-old. On gross and microscopic examination, formation of primary atheroscleotic lesions could be delated and/or prevented patially by effets of these drugs. On morphometric examination, failure to remodel forming vascular stenosis could not be seen, though relatively mild atherosclerotic lesion occured at vascular tree. These data suggest that the stenotic process in advanced atherosclerotic vessels can be delayed and/or prevented by several drugs including methotrexate, probucol, sulodexide, diltiazem, cilazapril, trimetazidine, molsidomine, pentoxiphylline and Ginexin (R) in vivo state.
Animals ; Aorta ; Apolipoproteins ; Apolipoproteins E* ; Atherosclerosis ; Cilazapril ; Constriction, Pathologic ; Diltiazem ; Humans ; Infant ; Methotrexate ; Mice ; Mice, Knockout* ; Molsidomine ; Popliteal Artery ; Primary Prevention ; Probucol ; Trimetazidine

BACKGROUND: We observed the changes of clinical characteristics after oral Molsidomine, a nitric oxide donor, in patients who have documented coronary artery spasm by ergonovine coronary angiogram and refractory to conventional anti-anginal therapy. METHOD: Molsidomine, oral nitric oxide donor, was administrated over 12 weeks in 20 patients (6 male, 14 female, 54+/-11.5 years) in order to observe the clinical effects in patients with coronary artery spasm unresponsive to nitrate and calcium channel blockers. Changes in the frequency of pain and sublingual nitroglycerin use, blood pressure, heart rate, side effects, electrocardiogram, and laboratory findings were evaluated before and after Molsidomine therapy. RESULTS: The frequencies of pain and sublingual nitroglycerin use were 3.9+/-0.9/week before treatment and decreased to 2.9+/-0.9/week at 4th week after the additional Molsidomine treatment (pre-treatment vs. 4th week; p<0.001), to 1.0+/-0.8/week at 8th week (4th week vs. 8th week; p<0.001), and to 0.7+/-0.8/week at 12th week. Systolic blood pressure decreased after treatment, but there were no significant changes in diastolic blood pressure, heart rate, resting electrocardiogram and laboratory findings. Molsidomine was discontinued in one patient because of headache. CONCLUSIONS: Molsidomine is an effective and well tolerated anti-ischemic agent in patients with variant angina refractory to conventional anti-anginal therapy.
Blood Pressure ; Calcium Channel Blockers ; Coronary Vessels ; Electrocardiography ; Ergonovine ; Female ; Headache ; Heart Rate ; Humans ; Male ; Molsidomine ; Nitric Oxide* ; Nitroglycerin ; Spasm ; Tissue Donors*

The present investigation tested the hypothesis that the activation of protein kinase G (PKG) leads to a phosphorylation of Ca2+-activated potassium channel (KCa channel) and is involved in the activation of KCa channel activity in cerebral arterial smooth muscle cells of the rabbit. Single-channel currents were recorded in cell-attached and inside-out patch configurations of patch-clamp techniques. Both molsidomine derivative 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1, 50 micrometer) and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP, 100 micrometer), a membrane-permeable analogue of cGMP, increased the KCa channel activity in the cell-attached patch configuration, and the effect was removed upon washout of the drugs. In inside-out patches, single-channel current amplitude was not changed by SIN-1 and 8-pCPT-cGMP. Application of ATP (100 micrometer), cGMP (100 micrometer), ATP+cGMP (100 micrometer each), PKG (5 U/ microliter), ATP (100 micrometer)+PKG (5 U/ microliter), or cGMP (100 micrometer)+PKG (5 U/ microliter) did not increase the channel activity. ATP (100 micrometer)+cGMP (100 micrometer)+PKG (5 U/ microliter) added directly to the intracellular phase of inside-out patches increased the channel activity with no changes in the conductance. The heat-inactivated PKG had no effect on the channel activity, and the effect of PKG was inhibited by 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP, 100 micrometer), a potent inhibitor of PKG or protein phosphatase 2A (PP2A, 1 U/ml). In the presence of okadaic acid (OA, 5 nM), PP2A had no effect on the channel activity. The KCa channel activity spontaneously decayed to the control level upon washout of ATP, cGMP and PKG, and this was prevented by OA (5 nM) in the medium. These results suggest that the PKG-mediated phosphorylations of KCa channels, or some associated proteins in the membrane patch increase the activity of the KCa channel, and the activation may be associated with the vasodilating action.
Adenosine Triphosphate ; Cyclic GMP-Dependent Protein Kinases ; Membranes ; Molsidomine ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Okadaic Acid ; Patch-Clamp Techniques ; Phosphorylation ; Potassium Channels* ; Potassium* ; Protein Phosphatase 2 ; Signal Transduction*

BACKGROUND: Nitric oxide (NO) production has been described as a double-edged sword eliciting both pro-and anti-inflammatory effect s in different immune reactions. This work was undertaken to investigate the immunoregulatory role of NO in experimental allergic encephalomyelitis (EAE) and experimental allergic uveitis (EAU). MEHHOD: We examined whether molsidomine (MSDM), a NO donor, administration to the myelin basic protein (MBP)-or interphotoreceptor retinoid binding protein (IRBP)-immunized rat s could suppress EAE development by shifting toward the Th2 cytokine response. In the EAE experiment s, the rat s were treated orally with MSDM (10 mg/kg/day) at the early stage (-1-4 days) or throughout the experimental period (-1-15 days). RESULTS: This resulted in significant amelioration of the disease and mild clinical symptoms, while MBP-immunization without MSDM administration showed severe EAE development . A marked reduction in inflammation was also observed in the spinal cord, indicating the crucial role of NO in the pathogenesis of EAE in in vivo. In the EAU experiments, a 24 h pre-treatment with MSDM prior to IRBP immunization resulted in significant inhibition of the disease. Furthermore, MSDM administration for 2 1 days completely reduced the incidence and severity of EAU. To investigate whether MSDM could modulate cytokine switching from Th 1 to Th2, culture supernatants of MBP-or IRBP-stimulated inguinal lymphocytes were analyzed. MSDM treatment enhanced IL-10 secretion but decreased IFN-gamma. IL-4 was undetectable in all groups. In contrast, the MBP-or IRBP-immunized rat s without MSDM secreted high concentrations of IFN-gamma, but low concentrations of IL-10. CONCLUSION: In conclusion, NO administation suppresses EAE and EAU by modulating the Th 1/Th2 balance during inflammatory immune responses. This work further suggest s that NO may be useful in the therapeutic control of autoimmune disease.
Animals ; Autoimmune Diseases* ; Carrier Proteins ; Encephalomyelitis, Autoimmune, Experimental ; Humans ; Immunization ; Incidence ; Inflammation ; Interferon-gamma ; Interleukin-10 ; Interleukin-4 ; Lymphocytes ; Molsidomine ; Myelin Basic Protein ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Rats ; Spinal Cord ; Tissue Donors ; Uveitis