Metformin is an oral antidiabetic drug in the biguanide class, which is used for type 2 diabetes. The side effects of metformin are mostly limited to digestive tract symptoms, such as diarrhea, flatulence and abdominal discomfort. The most serious potential adverse effect of metformin is lactic acidosis. A 51-year-old man was admitted due to hypoglycemia as a result of an overdose of antidiabetic drugs. He took massive dose of metformin. Conservative treatment failed for metabolic acidosis without lactic acidosis accompanied by acute kidney injury. Hemodialysis was executed to correct the high anion gap metabolic acidosis and acute kidney injury, and the patient recovered fully from metabolic acidosis. This case illustrates that the presence of clinical conditions, such as metformin-induced acute kidney injury and metabolic acidosis, can be developed without lactic acidosis. Prompt recognition of metabolic acidosis and early intervention with hemodialysis can result in a successful clinical outcome.
Acid-Base Equilibrium ; Acidosis ; Acidosis, Lactic ; Acute Kidney Injury ; Diarrhea ; Early Intervention (Education) ; Flatulence ; Gastrointestinal Tract ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Metformin ; Middle Aged ; Renal Dialysis

No abstract available.
Uterine Cervical Neoplasms*

PURPOSE: Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors. MATERIALS AND METHODS: Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-gamma production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed. RESULTS: Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-gamma production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells. CONCLUSION: IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer.
Adenoviridae ; Animals ; Carcinogenesis ; Coinfection ; Human papillomavirus 16 ; Humans* ; Immunity, Cellular ; Immunization* ; Interleukin-12* ; Mice ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic ; Uterine Cervical Neoplasms

PURPOSE: An arsenical compound, As2O3, has been reported to be effective for treating acute leukemia and inducing apoptosis in many different tumor cells. In this study, the ability of As4O6 to suppress cell growth and induce gene expression patterns was tested using a cDNA microarray in HPV16 immortalized cervical carcinoma cells, SiHa cells, along with As2O3. MATERIALS AND METHODS: A novel arsenical compound, As4O6, was designed and its ability to induce cell growth inhibition as well as gene expression profiles along with As2O3 in HPV16 infected SiHa cervical cancer cells was compared. Both As2O3 and As4O6 induced apoptosis in SiHa cells, as determined by DNA ladder formation. To further compare the gene expression profiles between these two drugs, a 384 cDNA microarray system was employed. Also, the gene expression profiles were classified into the Gene Ontology (GO) to investigate apoptosis-related cellular processes. RESULTS: As4O6 was more effective i suppressing the growth of SiHa cells in vitro compared to As2O3. In the case of treatment with As2O3, 41 genes were up- or down- regulated at least 2 fold compared to non-treatment. However, 65 genes were up- or down-regulated by As4O6 treatment. In particular, 27 genes were commonly regulated by both arsenic compounds. Also, the GO analysis indicated that down-regulation of cell-regulatory functions, such as cell cycle, protein kinase activity and DNA repair, induced anti-tumor effect. CONCLUSION: These data support that As4O6 could be more effective than As2O3 in inhibiting the growth of HPV16 infected cervical cancer cells. This appears to be mediated through a unique, but overlapping regulatory mechanism(s), suggesting that the regulated genes and cellular processes could be further used as a new potential drug approach for treating cervical cancer in clinical settings.
Apoptosis ; Arsenicals ; Cell Cycle ; DNA ; DNA Repair ; Down-Regulation ; Gene Expression ; Gene Ontology ; Leukemia ; Oligonucleotide Array Sequence Analysis ; Protein Kinases ; Transcriptome ; Uterine Cervical Neoplasms*

It has been known that glassy cell carcinoma (GCC) of uterine cervix is rare and rapidly progressive, and has a poor prognosis. Here we describe a case of GCC in which photodynamic therapy (PDT) was performed prior to radical hysterectomy. The patient, a 42 year-old woman at the stage of FIGO Ib2 underwent interstitial PDT (Photogem, 2 mg/kg; light, p=100 mV, W=100 J/cm2, 15 min/each 4 direction). The cervical lesion displayed inflammation and necrosis at 48 h following PDT. At 2 weeks post PDT, inflammatory reaction was disappeared and the tumor volume was decreased. No side effects of PDT were also observed. Subsequently, the patient underwent radical hysterectomy and pelvic lymph node resection. This case suggests that PDT prior to radical surgery might be an effective way to reduce tumor size without any side effects. More cycles of PDT might be beneficial for treating GCC of the uterine cervix.
Adult ; Cervix Uteri* ; Drug Therapy ; Female ; Humans ; Hysterectomy ; Inflammation ; Lymph Nodes ; Necrosis ; Photochemotherapy* ; Prognosis ; Tumor Burden

OBJECTIVE: We tried to confirm the effects of green tea extracts (polyphenon E, EGCG) in patients with human papilloma virus (HPV) positive cervical lesion. METHODS: We divided 51 HPV positive cervical lesion patients (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) into 4 group and 37 patient as placebo control. We applied poly E ointment two times per week (27 patients), poly E ointment plus poly E capsule (8 patients), poly E capsule (6 patients), EGCG capsule (10 patients) 200 mg each for 8 to 12 weeks. RESULTS: Among 27 patients with poly E ointment group, 20 patients responded (74%), such as chronic cervicitis (12/18), mild dysplasia (4/5), moderate dysplasia (2/2) and severe dysplasia (1/2). Among 8 patients with poly E ointment and poly E capsule group, 6 patients responded (75%), 6 patients poly E capsule group responded 3 patients (50%). 10 EGCG capsule patients group responded 6 patients (60%). Overall responsive rate is 69% (35/51) in case of green tea extracted treated group and 10% (4/39) in placebo controlled group (P<0.05). CONCLUSION: The effects of green tea extract in HPV positive cervical lesion were statistically significant (P<0.05). This result suggests that green tea extract has highly potential of new treatment agent for HPV infected cervical lesion.
Humans* ; Papilloma* ; Tea* ; Uterine Cervical Neoplasms ; Uterine Cervicitis

BACKGROUND: Brief myocardial ischaemia has been demonstrated to result in mechanical and coronary endothelial dysfunction. We examined whether the mechanical and vascular responses to amrinone are altered in the postischaemic, reperfused myocardium. The effects of amrinone were compared with those of dobutamine. METHODS: In an open-chest canine model, coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and regional mechanical function in response to either amrinone (2, 5, 7.5, and 10 ng/mL of CBF) or dobutamine (0.05, 0.125, 0.25, 0.375, and 10ng/mL of CBF) directly infused into the left anterior descending (LAD) artery were determined before (normal) and 30 min after 15-min- period of LAD occlusion (stunned). Percent segment shortening (%SS), peak segment lengthening rate (dL/dt(max)), and percent post-systolic shortening (%PSS) in the LAD territory was determined using ultrasonic crystals and CBF using Doppler transducer. Myocardial extractions of oxygen (EO2) and lactate (Elac) were calculated. RESULTS: Both amrinone and dobutamine in the normal myocardium caused a dose-dependent increase in mechanical functions (%SS and dL/dt(max)) and MVO2 that were comparable (range, 20 40%), but they had no effects on %PSS. Amrinone caused an increase of CBF in excess of MVO2, resulting in a modest decrease in EO2, whereas dobutamine increased CBF in proportion to MVO2, resulting in no changes in EO2. The ischemia and reperfusion insult reduced %SS, dL/dt(max), and Elac, while it did not affect mechanical (%SS and dL/dt(max)) and CBF responses to either agent, except for progressive reductions of %PSS. CONCLUSIONS: These results indicate that amrinone, similar to dobutamine, exert positive inotropic and lusitropic effects in normal and stunned canine myocardium. It is also indicated that amrinone causes direct coronary vasodilation, which is not affected by an ischemia and reperfusion insult.
Amrinone* ; Animals ; Arteries ; Dobutamine ; Dogs* ; Ischemia ; Lactic Acid ; Myocardial Stunning* ; Myocardium ; Oxygen Consumption ; Oxygen* ; Reperfusion ; Reperfusion Injury ; Transducers ; Ultrasonics ; Vasodilation

BACKGROUND: During one lung ventilation (OLV) for thoracic surgery, hypoxic pulmonary vasoconstriction (HPV) may reduce venous admixture and ameliorate the decrease in arterial oxygenation by diverting blood from the non-ventilated to the ventilated lung. Volatile anesthethics are the drugs of choice in thoracic surgery despite numerous experimental data showing their inhibiting effect on the HPV. The effect of thoracic epidural anesthesia (TEA) on HPV during OLV has not been determined. The object of the present study was to compare the effects of TEA with those of isoflurane on oxygenation and shunting during two lung ventilation (TLV) and OLV in human volunteers. METHODS: Thirty patients who needed OLV for elective thoracic surgery were randomly assigned to receive either group isoflurane (1 MAC isoflurane + saline 6 ml TEA + 0.5 - 1ng/dl propofol + fentanyl + vecuronium, n = 15) and group TEA (0.5% bupivacaine 6 ml TEA + 0.5 - 1ng/dl propofol + fentanyl + vecuronium, n = 15) with 100% oxygen in separate groups. Systemic hemodynamic parameters were recorded, and blood gas values were obtained 30 min after the start of TLV and 30, 45 and 60 min after the start of OLV in the lateral position. RESULTS: Reductions in PaO2 and increases in shunt fraction at all study times after the start of OLV were observed. However, there were no differences in percentage changes between the groups. The other blood gas data (SaO2, SO2, PaCO2, PCO2, pH, Hb, CaO2, CO2) and systemic hemodynamics (mean arterial blood pressure, central venous pressure) did not change at all the study times after the start of OLV in the two groups. CONCLUSIONS: In clinical practice, isoflurane and TEA for OLV was no different in terms of arterial blood oxygenation and pulmonary shunt.
Anesthesia* ; Anesthesia, Epidural* ; Arterial Pressure ; Bupivacaine ; Fentanyl ; Healthy Volunteers ; Hemodynamics ; Humans ; Hydrogen-Ion Concentration ; Isoflurane* ; Lung* ; One-Lung Ventilation ; Oxygen* ; Propofol ; Tea ; Thoracic Surgery ; Vasoconstriction ; Vecuronium Bromide ; Ventilation

Radial artery is frequently chosen for cannulation. Although the method is safe and simple, it can infrequently lead to tissue necrosis. This is a report of one case of amputation due to thumb necrosis developed from the radial artery cannulation in a patient who had open heart surgery. This is a 65 years old female who received a graft interposition of ascending aorta due to dissecting aortic aneurysm. Left radial artery cannulation was carried out after modified Allen's test appeared to be positive. On the 11 th postoperative days, we found that the catheter of left hand was obstructed, and we removed the catheter. On the 9 hrs after removal of catheter, thumb of left hand became color change and edematous with blister. On the 14 th days after removal of catheter, thumb of left hand became worsened to dusky purple to dark color change and pulseless, coldness. On the 20 th days after removal of catheter, amputation of thumb of left hand was performed.
Aged ; Amputation ; Aorta ; Aortic Aneurysm ; Blister ; Catheterization* ; Catheters ; Female ; Hand ; Humans ; Necrosis* ; Radial Artery* ; Thoracic Surgery ; Thumb* ; Transplants

BACKGROUND: Myocardial ischemia is known to depress systolic and diastolic functions for a prolonged period of time. Dobutamine and epinephrine are frequently administered to improve myocardial function during cardiac surgery. The vascular response to vasopressors might be altered by ischemia and reperfusion, since alterations in vascular control mechanisms have been demonstrated even after a short period of ischemia. The present study was aimed to investigate the effects of dobutamine and epinephrine on regional and global myocardial functions, coronary blood flow (CBF) and myocardial oxygen consumption (MVO2) in normal and stunned myocardium in an open-chest canine model. METHODS: Forty-eight dogs were acutely instrumented under enflurane anesthesia to measure aortic and left ventricular pressures, and pulmonary (cardiac output) and left anterior descending (LAD) blood flows via a Doppler flowmeter, and a subendocardial segment length in the region supplied by the LAD. In series 1, incremental doses of dobutamine (1, 2, 5, 10microgram/kg/min, n = 9) or epinephrine (0.02, 0.04, 0.1, 0.2microgram/kg/min, n = 10) were infused intravenously (IV) for 10 min before (normal) and after 15 min of LAD occlusion and subsequent 1 hr-reperfusion (stunned). In series 2, incremental doses of dobutamine (50, 125, 250, 375 ng/mL of LAD flow, n = 14) or epinephrine (4, 10, 20, 30 ng/mL of LAD flow, n = 15) were infused directly into the LAD (IC) for 3 5 min before (normal) and after myocardial ischemia (stunned). Segment shortening (%SS), as an index of regional myocardial contractility, and the peak segment lengthening rate (dL/dt max), as an index of regional diastolic function, were evaluated. Simultaneous arterial and coronary venous contents of oxygen and lactate were measured to calculate MVO2 and oxygen (EO2) and lactate extraction (Elac) ratios during IV or IC infusions of epinephrine or dobutamine. Effectiveness of metabolic vasodilation was determined from EO2. RESULTS: IV or IC infusions of dobutamine or epinephrine before ischemia resulted in dose-dependent increases in mechanical functions (%SS and dL/dt max) and MVO2. These changes were accompanied by parallel increases in CBF resulting in unaltered EO2 with an infusion of dobutamine, while CBF increased more than MVO2 with epinephrine, resulting in decreased EO2. After the ischemia and reperfusion, %SS and dL/dt max were depressed and Elac was reduced, but similar mechanical responses (%SS and dL/dt max) to both dobutamine & epinephrine were observed. Also, in the stunned myocardium, CBF increased in parallel with mechanical function and MVO2 with either IC or IV dobutamine, resulting in an unaltered EO2. However, IC but not IV epinephrine did not affect EO2, suggesting abolishment of its direct vasodilating effect in stunned myocardium. In addition, IC epinephrine infusion further decreased Elac, while IC dobutamine did not affect it in stunned myocardium. During IV infusions, dobutamine caused a dose-dependent increase in the heart rate but epinephrine did not affect it, despite the comparable increase in cardiac index and mean aortic pressure. CONCLUSIONS: The results indicate that dobutamine and epinephrine exert similar positive inotropic and lusitropic effects in normal and stunned myocardium in dogs. However, epinephrine causes direct coronary vasodilation in normal myocardium, but it does not directly affect coronary vascular tone in stunned myocardium. In addition, epinephrine infusion dose-dependently depresses Elac in stunned myocardium. In contrast, dobutamine affects neither direct coronary vascular tone nor Elac regardless of ischemia and reperfusion injury.
Anesthesia ; Animals ; Arterial Pressure ; Dobutamine* ; Dogs* ; Enflurane ; Epinephrine* ; Flowmeters ; Heart Rate ; Ischemia ; Lactic Acid ; Myocardial Ischemia ; Myocardial Stunning* ; Myocardium ; Oxygen Consumption ; Oxygen* ; Reperfusion ; Reperfusion Injury ; Thoracic Surgery ; Vasodilation ; Ventricular Pressure