Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event?

BACKGROUND: The widespread use of the fluoroquinolones has raised the question of the cardiac safety of these medications. This widespread use of this class of antibiotics has displayed their safety profile, which is actually more favorable than many other drug classes. The cardiac toxicity issue at the center of this discussion is the prolongation of the QT interval leading to torsade de pointes. Ciprofloxacin and levofloxacin, two of the more commonly used fluoroquinolones, are considered less likely than other fluoroquinolones to prolong the QT interval. The authors set out to evaluate the effect on the QT interval of patients after administration of ciprofloxacin and levofloxacin. METHODS: A prospective evaluation of 38 consecutive patients evaluated by the infectious disease service and receiving either ciprofloxacin or levofloxacin was undertaken. Twelve-lead electrocardiograms were obtained at baseline and at least 48 hours after the first dose of the antibiotic was administered. Both the longest QT interval and the mean QT interval were evaluated. To account for variations in heart rate, the corrected QT interval was calculated by using Bazett's formula (QTc = QT(square root of) R-R). Statistical analysis was undertaken to assess for the presence of a change after the administration of the antibiotic. RESULTS: Thirty-eight patients (mean age, 65 +/- 19 years), 23 women and 15 men, were studied. There was a small but significant increase in the longest QTc intervals over baseline in patients receiving levofloxacin; there was no significant change in the mean QTc interval. However, one patient who received levofloxacin was, statistically, an outlier and, on retrospective analysis, had demonstrated severe electrolyte disturbances at the time of the study. When this patient was excluded, the increase in the longest QTc interval was not significant. Patients receiving ciprofloxacin did not demonstrate any significant change in the longest QTc interval or mean QTc interval. CONCLUSIONS: Neither levofloxacin nor ciprofloxacin significantly prolonged the mean QTc interval over baseline. When electrolyte deficiencies in one of the patients evaluated were taken into account, this also held true for the longest QTc interval. There is, therefore, evidence that taking ciprofloxacin or levofloxacin, assuming that there are not any concurrent risk factors, will not cause a significant prolongation in the QT interval.     

Dynamic left ventricular outflow tract obstruction induced by dobutamine stress echocardiography leading to myocardial ischemia and infarction

Left ventricular outflow tract (LVOT) obstruction occurring during dobutamine stress echocardiography (DSE) occurs in approximately 15-20% of patients undergoing DSE. The clinical significance and mechanism of LVOT obstruction has been debated, but is now generally felt to result from the pharmacological effects of dobutamine in increasing inotropy and causing peripheral vasodilation. It must be realized that in rare instances, ischemia may occur and lead to wall motion abnormalities and eventually myocardial infarction. We present the case of a 70-year-old asymptomatic woman who underwent a routine pre-operative cardiac stress evaluation and was found to develop a dynamic outflow tract obstruction leading to myocardial ischemia and infarction.     

Gingerol-derivatives: emerging new therapy against human drug-resistant MCF-7

Cancer chemotherapies have been improved dramatically over the last two decades. In the case of human breast cancer, the combination chemotherapeutic protocol, cyclophosphamide (CPA), doxorubicin (DOX), and 5-fluorouracil (5-FU) (CDF), is often used. Nevertheless, the clinical usefulness of CDF is limited by its remarkably low therapeutic window and frequent eruption of resistance. These limitations prompted our search for a more effective and safe drug candidate that may raise the therapeutic benefits for breast cancer patients. Gingerols’ wide therapeutic indices as well as their high efficacy in the suppression of carcinogenesis are well established. However, no thorough study to date has profiled their antibreast cancer activities in depth. Therefore, the aims of the present study are to evaluate the antibreast cancer activities of gingerols in comparison to CDF and to gain insight into the structure activity relationships (SARs) responsible for the observed effect using a breast cancer cell model, MCF-7. Our data revealed that 6-gingerol showed the highest anticancer potency that is superior to that of CDF with IC₅₀?=?30.4 μM. Guided by these results, semisynthetic modifications of 6-gingerol have been carried out to characterize 6-gingerol’s SARs. The obtained results showed that the acquisition of free hydroxyl group in the aliphatic side chain of 6-gingerol is essential for the antibreast cancer activity. Likewise, the length of aliphatic side chain in 6-gingerol is optimum for its anticancer activity because any decrease in the side chain length resulted in a dramatic loss of anticancer activity. Additionally, allylation of phenolic group has shown antibreast cancer activity superior to that of 6-gingerol per se. Conversely, methylation or isoprenylation of phenolic group has led to a potential decrease in the anticancer activity, whereas loss of aromaticity resulted in a complete loss of 6-gingerol’s cytotoxic activity. Collectively, the present results would simplify drug design to allow safer and more effective antibreast cancer pharmaceuticals to be designed.     

Susceptibility weighted imaging in infants with staged embolization of vein of Galen aneurysmal malformations

Background and purpose

The vein of Galen aneurysmal malformation (VGAM) is a rare congenital vascular malformation with a higher morbidity and mortality, especially in neonates. Ultrasound, CT and MR are usually used in diagnosis and treatment monitoring of these disorders. In this current study, we aim to examine utility of SWI in evaluation of treatment response in infants with VGAM.

Design and syntheses of diarylisoxazoles: Novel inhibitors of cyclooxygenase‐2 (COX‐2) with analgesic‐antiinflammatory activity

A group of 4,5‐diphenylisoxazoles ( 11a–p ), 3,4‐diphenyl‐5‐trifluoromethylisoxazoles ( 15, 21 ), and 4,5‐diphenyl‐3‐methylsulfonamidoisoxazole ( 23 ) possessing a variety of substituents (H, F, MeS, MeSO, MeSO₂) at the para‐position of one of the phenyl rings were synthesized for evaluation as analgesic, and selective COX‐2 inhibitory antiinflammatory (AI), agents. Although the 4,5‐diphenylisoxazole group of compounds (11a–p) exhibited potent analgesic and AI activities, those compounds evaluated ( 11a, 11b, 11m ) were more selective inhibitors of COX‐1 than COX‐2, with the exception of 4‐(4‐methylsulphonylphenyl)‐5‐phenylisoxazole ( 11n ) that showed a modest COX‐2 selectivity index (SI) of 2.1. In contrast, 3‐(4‐methylsulphonylphenyl)‐4‐phenyl‐5‐trifluoromethylisoxazole ( 15 ), which retained good analgesic and AI activities, was a highly potent and selective COX‐2 inhibitor (COX‐1 IC₅₀ > 500 μM; COX‐2 IC₅₀ < 0.001 μM) with a COX‐2 SI of > 500,000, relative to the reference drug celecoxib (COX‐1 IC₅₀ = 22.9 μM; COX‐2 IC₅₀ = 0.0567 μM) with a COX‐2 SI of 404. The 3‐phenyl‐4‐(4‐methylsulphonylphenyl) regioisomer ( 21 ) was a less potent inhibitor (COX‐1 IC₅₀ = 252 μM; COX‐2 IC₅₀ = 0.2236 μM) with a COX‐2 SI of 1122, relative to the regioisomer ( 15 ). The related compound 4,5‐diphenyl‐3‐methylsulfonamidoisoxazole ( 23 ) exhibited similar (to 21 ) potency and COX‐2 selectivity (COX‐1 IC₅₀ > 200 μM; COX‐2 IC₅₀ = 0.226 μM) with an SI of 752. A molecular modeling (docking) study for the most potent, and selective, COX‐2 inhibitor (15) in the active site of the human COX‐2 enzyme showed the C‐5 CF₃ substituent is positioned 3.37 Å from the phenolic OH of Tyr³⁵⁵, and 6.91 Å from the Ser⁵³⁰ OH. The S‐atom of the MeSO₂ substituent is positioned deep (7.40 Å from the entrance) inside the COX‐2 secondary pocket (Val⁵²³). These studies indicate a C‐5 CF₃ ( 15, 21 ), or C‐3 NHSO₂Me ( 23 ), central isoxazole ring substituent is crucial to selective inhibition of COX‐2 for this class of compounds. Drug Dev. Res. 51:273–286, 2000. © 2001 Wiley‐Liss, Inc.     

Coronary artery stent fracture

Coronary stent fracture is a rare but potentially serious complication of coronary artery stenting. In light of the non-specific presentation of stent fracture, it is also an easily missed complication. In order to ensure rapid recognition and treatment of this entity, physicians must be aware of its existence and its possibility under the right circumstances. We present the case of a 61-year-old Guyanese male who presented with unstable angina secondary to a stent fracture within two weeks of elective percutaneous coronary intervention (PCI) for in-stent restenosis.     

How does epidemiological and clinicopathological features affect survival after gastrectomy for gastric cancer patients-single Egyptian center experience

AIM: To investigate the clinicopathological features and the significance of different prognostic factors which predict surgical overall survival in patients with gastric carcinoma.METHODS: This retrospective study includes 80 patients diagnosed and treated at gastroenterology surgical center, Mansoura University, Egypt between February 2009 to February 2013. Prognostic factors were assessed by cox proportional hazard model.RESULTS: There were 57 male and 23 female. The median age was 57 years (24-83). One, 3 and 5 years survival rates were 71%, 69% and 46% respectively. The median survival was 69.96 mo. During the follow-up period, 13 patients died (16%). Hospital morbidity was reported in 10 patients (12.5%). The median number of lymph nodes removed was 22 (4-41). Lymph node (LN) involvement was found in 91% of cases. After R0 resection, depth of wall invasion, LN involvement and the number (> 15) of retrieved LN, LN ratio and tumor differentiation predict survival. In multivariable analysis, tumor differentiation, curability of resection and a number of resected LN superior to 15 were found to be independent prognostic factors.CONCLUSION: Surgery remains the cornerstone of treatment. Tumor differentiation, curability of resection and a number of resected LN superior to 15 were found to be independent prognostic factors. Extended LN dissection does not increase the morbidity or mortality rate but markedly improves long term survival.