In vitro cytotoxicity and phototoxicity of N-piperazinyl quinolone derivatives with a 2-thienyl group.

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA) irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6 having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4 position of piperazine ring of enoxacin showed the highest cytotoxicity potential on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml, respectively). While some of the other tested compounds exhibited clear phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential of phototoxicity. These findings suggest the high potential of 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic compound with low potency of phototoxic reactions. The mentioned chemical was identified to be of special interest for further characterization.     

Release of Proinflammatory Cytokines During Pediatric Cardiopulmonary Bypass: Heparin-Bonded Versus Nonbonded Oxygenators

Background. Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients.

Methods. Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB.

Results. Significant levels of tumor necrosis factor- were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01).

Conclusions. The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry.     

Clinical efficacy of codergocrine mesylate in children with learning difficulties

A double-blind placebo-controlled study in children showed codergocrine mesylate to be effective in improving cognitive functions and behavioural symptoms associated with learning disorders. Forty randomly grouped children of either sex were given an increasing dosage of codergocrine mesylate and followed up for 12 weeks. A significant improvement was noted in speech (acquisition of new words, comprehensibility/meaningfulness of speech), sociability, attention/concentration, comprehension and memory. Improvement in behaviour (emotional lability and cooperativeness) was also noted. Problems of assessing cognitive progress in very young children with culturally appropriate methods were encountered.     

Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: Evidence for loss of compartmentalization of contrast media

The purpose of this study was to characterize the contrast caused by a susceptibility MRI contrast agents, on spin echo T₂-weighted imaging of reperfused myocardial infarction. Our interest in this model focused on the expected requirement that such agents be compartmentalized in the tissue to cause signal loss on spin echo images, a condition which may not be present in reperfused infarcted myocardium. Accordingly, nine rats were subjected to 2 h of left coronary artery occlusion followed by 3 ± 0.5 h of reperfusion prior to administration of contrast media. Three sets of MR images were acquired: (a) baseline axial images at the midventricle, both T₁-weighted (TR/TE = 300/20) and T₂-weighted (TR/TE = 1500/60); (b) T₁-weighted images after administering a T₁-enhancing agent, Gd-DTPA-BMA (0.2 mmol/kg), to document that contrast media is delivered to the reperfused infarction; and (c) T₂-weighted images after administering the susceptibility agent, Dy-DTPA-BMA (1.0 mmol/kg). Gadolinium-enhanced T₁ images depicted reperfused infarction as regions with greatly enhanced signal intensity compared with unin-farcted myocardium, indicating that contrast agent was delivered to the infarcted zone. Dysprosium-enhanced T₁ images depicted the injury as a region of persistent signal intensity relative to depletion of signal in normal myocardium, consistent with failure of the contrast agent to cause signal loss. Similar infarction sizes were observed for unenhanced T₂-weighted images (33 ± 5%), gadolinium-enhanced T₁ weighted images (36 ± 5%) and postmortem staining (30 ± 6%); strong correlations (r > 0.9) were noted in comparisons of these data. Dysprosium-enhanced images exhibited a smaller region of differential signal presumed to be infarction (20 ± 5%, P < 0.05) and weak correlations (r < 0.75) with the other measurements. We conclude that the smaller infarction depicted on dysprosium-enhanced images is a subregion of the true infarction in which myocardial necrosis is sufficiently advanced that the agent is homogeneously distributed throughout all tissue compartments, preventing T₂*-dependent phase loss on spin echo images.     

TANDEM URETEROCYSTOPLASTY

Background : Bladder augmentation may be undertaken by using various gastrointestinal segments but their use is associated with a multitude of well-recognized complications. The mega-ureter has proven to be a satisfactory alternative; in patients with bilateral mega-ureters, both ureters may be used for this purpose. Methods : Seventeen patients had augmentation ureterocystoplasty, including three in whom both distal ureters were used in tandem. The latter included two patients with neurogenic bladder and one with bladder exstrophy. Results : Satisfactory augmentation was achieved in all patients undergoing tandem ureterocystoplasty. The neurogenic bladder patients are managed by urethral clean intermittent catheterization (CIC) and the exstrophy patient is managed by CIC of an appendico-vesicostomy (Mitrofanoff). All are continent. Conclusions : The mega-ureter provides an excellent source of augmentation material in patients with small non-compliant bladders. In those with bilateral mega-ureters, consideration should be given to using both ureters in tandem to achieve the maximum possible bladder capacity.     

Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices.

BACKGROUND. Endoscopic sclerotherapy is an accepted treatment for bleeding esophageal varices, but it is associated with substantial local and systemic complications. Endoscopic ligation, a new form of endoscopic treatment for bleeding varices, may be safer. We compared the effectiveness and safety of the two techniques. METHODS. In this randomized trial we compared endoscopic sclerotherapy and endoscopic ligation in 129 patients with cirrhosis who had proved bleeding from esophageal varices. Sixty-five patients were treated with sclerotherapy, and 64 with ligation. Initial treatment for acute bleeding was followed by elective retreatment to eradicate varices. The patients were followed for a mean of 10 months, during which we determined the incidence of complications and recurrences of bleeding, the number of treatments needed to eradicate varices, and survival. RESULTS. Active bleeding at the first treatment was controlled by sclerotherapy in 10 of 13 patients (77 percent) and by ligation in 12 of 14 patients (86 percent). Slightly more sclerotherapy-treated patients had recurrent hemorrhage during the study (48 percent vs. 36 percent for the ligation-treated patients, P = 0.072). The eradication of varices required a lower mean (+/- SD) number of treatments with ligation (4 +/- 2 vs. 5 +/- 2, P = 0.056) than with sclerotherapy. The mortality rate was significantly higher in the sclerotherapy group (45 percent vs. 28 percent, P = 0.041), as was the rate of complications (22 percent vs. 2 percent, P less than 0.001). The complications of sclerotherapy were predominantly esophageal strictures, pneumonias, and other infections. CONCLUSIONS. Patients with cirrhosis who have bleeding esophageal varices have fewer treatment-related complications and better survival rates when they are treated by esophageal ligation than when they are treated by sclerotherapy.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

A preliminary study on the enhancement of the osteointegration of a novel synthetic hydroxyapatite scaffold in vivo

Synthetic hydroxyapatite, a bioactive calcium phosphate, is clinically used as a bone replacement bioceramic because of its similarity in composition to bone mineral, biocompatibility, and osteoconductive nature. The aim of this study was to evaluate the bioactivity of a novel synthetic porous hydroxyapatite (PHA) in vivo in rabbit and to investigate the enhancement of its bioactivity and osteointegration. In the investigation reported here, insulin-like growth factor-I (IGF-I) has been used to enhance the bioactivity of PHA. Cylindrical PHA implants with or without IGF-I were implanted bilaterally in rabbit femurs. Fluorochrome bone markers were administered at 7-day intervals. The implants with the attached bone were retrieved at postmortem, 1 and 3 weeks after implantation, for histological and histomorphometric analysis. Undecalcified sections stained with toluidine blue showed new bone formation. Mineralization of the new bone formed in the interface, surrounding trabecular bone, and within the pores of the implants was studied. Lamellar bone mineral apposition rate (MAR) was assessed and compared among treatment groups, sham, PHA alone, and PHA with IGF-I (500 ng/implant), by fluorochrome label incorporation using UVL microscopy. We report for the first time, that the supplementation of PHA implants with IGF-I significantly increased new bone formation and MAR (6.58 +/- 0.08 microm/day) compared with implantation of PHA alone (4.08 +/- 0.05 microm/day) or sham operation (3.11 +/- 0.12 microm/day). These results suggest that synthetic PHA might provide a delivery system for bioactive agents to accelerate bone healing in orthopedic procedures.