Laherradurin Inhibits Tumor Growth in an Azoxymethane/Dextran Sulfate Sodium Colorectal Cancer Model In Vivo.

Colorectal cancer (CRC) is the third most common neoplasia in the world. Its mortality rate is high due to the lack of specific and effective treatments, metastasis, and resistance to chemotherapy, among other factors. The natural products in cancer are a primary source of bioactive molecules. In this research, we evaluated the antitumor activity of an acetogenin (ACG), laherradurin (LH), isolated from the Mexican medicinal plant Annona macroprophyllata Donn.Sm. in a CRC murine model. The CRC was induced by azoxymethane-dextran sulfate sodium (AOM/DSS) in Balb/c mice and treated for 21 days with LH or cisplatin. This study shows for the first time the antitumor activity of LH in an AOM/DSS CRC model. The acetogenin diminished the number and size of tumors compared with cisplatin; the histologic studies revealed a recovery of the colon tissue, and the blood toxicity data pointed to less damage in animals treated with LH. The TUNEL assay indicated cell death by apoptosis, and the in vitro studies exhibited that LH inhibited cell migration in HCT116 cells. Our study provides strong evidence of a possible anticancer agent for CRC.

Investigation of the DNA Damage and Oxidative Effect Induced by Venlafaxine in Mouse Brain and Liver Cells.

Venlafaxine is an antidepressant used worldwide. Therefore, studies to confirm its safe use are mandatory. This report evaluated the drug DNA damage capacity in the brain and liver of ICR mice, and its oxidative effect on DNA, lipids, and proteins, as well as the amount of nitrites, also in the brain and liver. Determinations were made at 2, 6, 12, and 24 h post-treatment, excluding DNA oxidation that was observed at 2 h. The tested doses of venlafaxine were 5, 50, and 250 mg/kg. The results showed DNA damage in the brain with the two more elevated doses of venlafaxine at 2 and 6 h post-treatment and also at 12 h in the liver. The comet assay plus the FPG enzyme showed DNA damage in both organs with all doses. The two high doses increased lipoperoxidation in the two tissues from 6 to 12 h post-administration. Protein oxidation increased with the three doses, mainly from 2 to 12 h, and nitrite content was elevated only with the high dose in the liver. The drug was found to affect both tissues, although it was more pronounced in the liver. Interestingly, DNA oxidative damage was observed even with a dose that corresponds to the therapeutic range. The clinical relevance of these findings awaits further investigations.

Is There a Difference in the Contamination Rates of Urine Samples Obtained by Bladder Catheterization and Clean-Catch Collection in Preschool Children?

OBJECTIVE: The objective of this study was to compare contamination rates in urine samples obtained by transurethral catheterization and clean-catch methods in preschool children aged 2 to 5 years. METHODS: A retrospective, chart review was performed on patients evaluated in our emergency department over a 6-month period who had a urine culture obtained by either transurethral catheterization or clean-catch methods. The charts were reviewed for urine bacterial colony counts and divided into positive, negative, or contaminated cohorts. Demographic data were collected as well. RESULTS: Four hundred sixty patients met inclusion for this study. Of these patients, there were 120 samples collected by catheter (26.1%) and 340 samples collected by clean-catch method (73.9%).Female patients comprised 73% of the eligible samples (n = 336), and 27% were male (n = 124). Contamination rates significantly varied by collection method (P < 0.0001), with only 9 contaminated catheter samples (7.5%) and 125 contaminated clean-catch samples (36.76%). Contaminated samples were found in 122 of 336 female urine samples (36.3%), and 12 of 124 male urine samples (9.7%). There were no associations found between contamination rates and age within either sex. CONCLUSIONS: Our study demonstrated a higher urine culture contamination rate in preschool age children in the clean-catch method group compared with the transurethral catheterization group. This finding was particularly strong within the female subset, which could partially be accounted for by the small male sample size.

Genotoxic and oxidative effect of duloxetine on mouse brain and liver tissues.

We evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.

Clinical experience with CorMatrix extracellular matrix in the surgical treatment of mitral valve disease.

OBJECTIVES: To determine the clinical utility of an acellular bioscaffold as a structural material for mitral valve repair (MVr). METHODS: This was a retrospective study of patients undergoing partial or subtotal leaflet replacement and/or leaflet extension to treat mitral regurgitation or acute endocarditis and/or reconstruction of atrial-ventricular continuity after annular decalcification. The material used for repair was a bioresorbable extracellular matrix (ECM) material indicated for cardiac tissue repair (CorMatrix Cardiovascular, Inc, Roswell, Ga). After the necessary debridement, the ECM bioscaffold was tailored and sewn to the native mitral valve tissue. Intraoperative photographs and serial, follow-up echocardiograms were used for evaluation. RESULTS: From September 2008 to February 2013, MVr requiring the addition of patch material was performed in 19 patients. The median echocardiographic follow-up was 10.9 months (range, 4 days to 48 months). One early and 2 late deaths were unrelated to MVr. No perioperative or late strokes occurred. Two patients with a history of cancer, chemotherapy, and radiotherapy experienced failure of the initial MVr, necessitating reintervention. The other MVrs continued to show good valvular function and no calcification on echocardiographic follow-up of 4 days to 48 months. CONCLUSIONS: The ECM bioscaffold is a satisfactory material for MVr in a variety of surgical situations, including endocarditis. It appears to resist calcification and infection. Additional studies are warranted to determine the long-term durability of repairs made with ECM, and its appropriate use in patients who have previously undergone radiotherapy or chemotherapy.

Invasive renal cell carcinoma with inferior vena cava tumor thrombus: cardiac anesthesia in liver transplant settings.

OBJECTIVES: Resection of renal cell carcinomas (RCC) with tumor thrombus invasion into the inferior vena cava (IVC) is associated with significant perioperative morbidity and mortality. This study examined the intra- and inter-departmental collaboration among cardiac, liver transplantation, and urologic surgeons and anesthesiologists in caring for these patients. DESIGN: After IRB approval, medical records of patients who underwent resection of RCC tumor thrombus level III and IV, from 1997 to 2010 in this institution, were reviewed. Data were collected and analyzed by one way-ANOVA and chi-square test. SETTING: Major academic institution, tertiary referral center. PARTICIPANTS: This was a retrospective study based on the medical records of patients who underwent resection of RCC tumor thrombus level III and IV, from 1997 to 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-eight patients (82.9%) with level III thrombus and 12 patients (17.1%) with level IV thrombus were analyzed. Sixty-five (92.9%) did not require any extracorporeal circulatory support; 5 (2 with level III and 3 with level IV; 7.1%) required cardiopulmonary bypass. No patients required veno-venous bypass. Compared to patients with level III thrombus extension, patients with level IV had higher estimated blood loss (6978±2968 mL v 1540±206, p<0.001) and hospital stays (18.8±1.6 days v 8.1±0.7, p<0.001). Intraoperative transesophageal echocardiography (TEE) was utilized in 77.6% of patients with level III thrombus extension and in 100% of patients with level IV thrombus extension. Intraoperative TEE guidance resulted in a significant surgical plan modification in 3 cases (5.2%). Short-term mortality was low (n = 3, 4.3%). CONCLUSIONS: Utilization of specialized liver transplantation and cardiac surgical techniques in the resection of RCC with extension into the IVC calls for a close intra-and interdepartmental collaboration between surgeons and anesthesiologists. The transabdominal approach to suprahepatic segments of the IVC allowed avoidance of extracorporeal circulatory support in most of these patients. Perioperative management of these patients reflected the critical importance of TEE-proficient practitioners experienced in liver transplantation and cardiac anesthesia.

Factors which predict safe extubation in the operating room following cardiac surgery.

BACKGROUND: Extubation in the operating room (OR) after cardiac surgery is hampered by safety concerns, psychological reluctance, and uncertain economic benefit. We have studied the factors affecting the feasibility of extubation in the OR after cardiac surgery and its safety. METHODS: The outcomes of 78 patients extubated in the OR after open heart surgery were retrospectively compared to a matched control group of 80 patients with similar demographics, co-morbidities, and operative procedures, that were performed over the same time period, but extubated in the intensive care unit (ICU) following a standard weaning protocol. Variables collected included the incidence of subsequent unplanned tracheal reintubation in the ICU, postoperative complications, need for mediastinal re-exploration, surgical and OR times, and ICU and hospital lengths of stay. RESULTS: Out of a total of 372 cardiac procedures performed during the designated time frame, 78 (21%) resulted in extubation in the OR, mostly after off-pump coronary revascularization (41%) and aortic valve replacement (19.4%). Preoperative hypertension, EF ≥30%, off-bypass revascularization and shorter surgical times increased the likelihood of extubation in the OR. Extubation in the OR did not increase perioperative morbidity and mortality rates, but decreased the length of ICU and hospital stays. The incidence of unanticipated subsequent tracheal intubation in the ICU was comparable to noncardiac high-risk procedures (2.5%). CONCLUSIONS: Extubation in the OR can be safely performed in a select group of cardiac surgery patients without any increase in postoperative morbidity or mortality. The proposed mathematical model performed reasonably well in predicting a successful extubation in the OR.

A randomized, controlled trial on dexmedetomidine for providing adequate sedation and hemodynamic control for awake, diagnostic transesophageal echocardiography.

OBJECTIVE: Transesophageal echocardiography (TEE) has become established as a sensitive and accurate diagnostic method for the rapid assessment of myocardial function. It was theorized that dexmedetomidine (Precedex; Hospira, Inc, Lake Forest, IL) might prove to be useful for sedating patients while undergoing TEE. DESIGN: A prospective, randomized trial was designed comparing dexmedetomidine versus standard therapy (eg, midazolam and opioids) for sedation. SETTING: This trial was performed in a tertiary care, single-institution university hospital. PARTICIPANTS: Males and females, American Society of Anesthesiologists I to IV, ages 18 to 65 years, requiring diagnostic TEE. Patients were excluded if pregnant, if they had taken benzodiazepines or opioids within 24 hours, or if they were deemed to be too unstable to receive any kind of sedation. INTERVENTIONS: Patients were randomized to standard therapy or dexmedetomidine infusion groups. Sedation was assessed at 6 time points. Pulse oximetry, electrocardiogram, heart rate, noninvasive blood pressure, and respiratory rate were monitored. Additional variables measured were the amount of each drug given, the time of the TEE procedure, and the time to recovery. MEASUREMENTS AND MAIN RESULTS: A survey about the quality of sedation, the level of comfort, and whether or not they would accept this type of sedation again was administered after recovery from sedation. Demographic data and patient questionnaire responses were reported as means and standard errors or percents and were analyzed with the t test and chi-square test. Twenty-two patients were enrolled. Hemodynamics were statistically different between the two groups at several time points. Both systolic and diastolic blood pressures (BP) were elevated in the standard therapy group, whereas the dexmedetomidine group had a lower BP. Heart rate was elevated significantly in the standard therapy group compared with the dexmedetomidine group. There was no statistical or clinical difference between the groups in terms of oxygenation or respiratory rate. CONCLUSIONS: The authors concluded that dexmedetomidine appears equivalent in achieving adequate levels of sedation without increasing the rate of respiratory depression or decreasing oxygen saturation compared with standard therapy, and it may be better in achieving desired hemodynamic results.

Surgical technique of removal of inferior vena cava leiomyosarcoma extending into the right atrium without deep hypothermic circulatory arrest.

BACKGROUND: Leiomyosarcoma of the inferior vena cava is a rare tumor with potential for significant morbidity and mortality. Surgical extirpiration remains the optimal treatment choice. A case of caval leiomyosarcoma with right atrial extension is presented with management techniques and literature review. METHODS: A 54 year old woman with constitutional symptoms was found to have advanced caval leiomyosarcoma with atrial extension. Surgical excision was performed without deep hypothermic circulatory arrest (DHCA), including right nephrectomy, adrenalectomy, and en-bloc resection of the vena cava along with Gore-Tex interposition graft. RESULTS: There were no operative complications. The patient was extubated on postoperative day one. Renal function remained normal. Final pathology was high grade leiomyosarcoma. Margins were negative. The patient is well at latest follow up. CONCLUSION: Resection of extensive caval leiomyosarcoma allows the best chance of cure and is possible without DHCA. Perioperative planning and coordination and adherence to oncologic techniques is critical.

Renal carcinoma with supradiaphragmatic tumor thrombus: avoiding sternotomy and cardiopulmonary bypass.

BACKGROUND: Renal cell carcinoma with tumor thrombus extension into the inferior vena cava (IVC) is rare. Surgical resection provides the only reasonable chance for cure, but the approach poses a challenge to the surgical team. We describe our technique to safely resect these tumors through a transabdominal incision that exposes the intrapericardial IVC and right atrium (RA) transdiaphragmatically, without the use of sternotomy, cardiopulmonary bypass (CBP), or deep hypothermic circulatory arrest (DHCA). Clinical outcomes of these patients and techniques are reported. METHODS: Between May 1997 and January 2009, 102 patients (mean age, 63 years) underwent resection of renal tumor extending into the IVC by techniques developed to avoid sternotomy and CBP. The tumor thrombus in 12 patients (13%) extended into the supradiaphragmatic IVC and RA. RESULTS: Complete resection was successful through the transabdominal approach without CBP in all patients. Mean operative time was 8 hours 15 minutes. Estimated blood loss was 2960 mL, and a mean of 9 U of blood was transfused. Two patients died postoperatively, 1 on day 4 of arrhythmia and 1 on day 22 of multisystem organ failure. All discharged patients were alive at the last follow-up. Three patients had tumor recurrence and have been referred for adjuvant therapy. CONCLUSIONS: In select cases, renal cell carcinoma extending into the IVC to the intrapericardial level and RA can be resected without sternotomy, CBP, or DHCA.

Successful use of a custom-made paracorporeal total artificial heart as a bridge to retransplantation in adult and adolescent patients.

Because the currently available total artificial hearts are rather bulky, the use of a custom-made paracorporeal total artificial heart constructed with 2 ventricular assist devices is an alternative for children and adults with small stature. This article reports our experience using this system in an adult and a pediatric patient. The advantages and disadvantages of this technique are discussed.

Evaluation of stage acoustics in Seoul Arts Center Concert Hall by measuring stage support.

Stage acoustics is an important characteristic for concert halls, both for the acoustic quality on stage and for the audience. However, relatively little research has been conducted into the question. This study was based on the investigation of an actual concert hall stage, that of the Seoul Arts Center Concert Hall in Korea. The stage acoustics was evaluated in the actual hall, and with two models: a 1:25 scale model and a computer model. The study was based on the stage support parameter ST1 proposed by Gade as a measure of support for individual performers [Acustica 65, 193-203 (1989)]. The variation of support was measured on the empty stage of the actual hall and in the two models. The effect of musicians on stage, the effect of moving the orchestra, the effect of ceiling height and of stage-wall profile were also investigated. Conclusions are drawn both relating to the Seoul Concert Hall stage and stages in general.

A systematic review of the comparative safety of colloids.

HYPOTHESIS: Safety differences exist among colloids widely used for fluid management in acutely ill patients, as judged according to the comparative incidence of adverse events. DATA SOURCES: Colloid safety data for human subjects were sought, without language or time period restrictions, by means of computer searches of bibliographic and clinical trial databases, hand searches of medical journals and Index Medicus, inquiries with investigators and colloid suppliers, and examination of reference lists. Search terms included "colloids", "morbidity", and "mortality". STUDY SELECTION: Controlled trials, cohort studies, pharmacovigilance studies, and prior meta-analyses were independently selected by 2 unblinded investigators. Of 189 candidate studies, 113 were included, with safety data encompassing 1.54 x 10(6) patients and 1.09 x 10(8) colloid infusions. DATA EXTRACTION: Two unblinded investigators independently extracted data. Study limitations and confounding factors were tabulated. DATA SYNTHESIS: With albumin as the reference colloid, the incidence rate ratio for anaphylactoid reactions was 4.51 (95% confidence interval, 2.06-9.89) after hydroxyethyl starch administration, 2.32 (95% confidence interval, 1.21-4.45) after dextran, and 12.4 (95% confidence interval, 6.40-24.0) after gelatin. Pruritus occurrence was significantly increased by hydroxyethyl starch exposure (odds ratio, 1.78; 95% confidence interval, 1.23-2.58). Artificial colloid administration was consistently associated with coagulopathy and clinical bleeding, most frequently in cardiac surgery patients receiving hydroxyethyl starch. On the basis of large-scale pharmacovigilance study results, albumin infusion resulted in a low rate of both total adverse events (3.1 to 8.6 per 10(5) infusions) and serious adverse events (1.29 per 10(6) infusions). CONCLUSIONS: Significant safety differences exist among colloids. Therefore, conclusions regarding the clinical usefulness of colloids as a fluid class should be formed with caution.