Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine

Background  Resistance to drug is a major cause of treatment failure in pediatric brain cancer. The multidrug resistance (MDR) phenotype can be mediated by the superfamily of adenosine triphosphate-binding cassette (ABC) transporters. The dynamics of expression of the MDR genes after exposure to chemotherapy, especially the comparison between pediatric brain tumors of different histology, is poorly described. Objective  To compare the expression profiles of the multidrug resistance genes ABCB1, ABCC1, and ABCG2 in different neuroepithelial pediatric brain tumor cell lines prior and following short-term culture with vinblastine. Methods  Immortalized lineages from pilocytic astrocytoma (R286), anaplasic astrocytoma (UW467), glioblastoma (SF188), and medulloblastoma (UW3) were exposed to vinblastine sulphate at different schedules (10 and 60 nM for 24 and 72 h). Relative amounts of mRNA expression were analyzed by real-time quantitative polymerase chain reaction. Protein expression was assessed by immunohistochemistry for ABCB1, ABCC1, and ABCG2. Results  mRNA expression of ABCB1 increased together with augmenting concentration and time of exposure to vinblastine for R286, UW467, and UW3 cell lines. Interestingly, ABCB1 levels of expression diminished in SF188. Following chemotherapy, mRNA expression of ABCC1 decreased in all cell lines other than glioblastoma. ABCG2 expression was influenced by vinblastine only for UW3. The mRNA levels showed consistent association to protein expression in the selected sets of cell lines analyzed. Conclusions  The pediatric glioblastoma cell line SF188 shows different pattern of expression of multidrug resistance genes when exposed to vinblastine. These preliminary findings may be useful in determining novel strategies of treatment for neuroepithelial pediatric brain tumors. Financial support: FAPESP (grant 2007/04065-9).     

Six-minute walk test: functional capacity of severely obese before and after bariatric surgery

BackgroundThe 6-minute walk test (6MWT) is a well-known instrument for assessing the functional capacity of a variety of groups, including the obese. It is a simple, low-cost and easily applied method to objectively assess the level of exercise capacity. The aim of the present study was to study the functional capacity of a severely obese population before and after bariatric surgery.MethodsA total of 51 patients were studied. Of the 51 patients, 86.2% were women, and the mean age was 40.9 ± 9.2 years. All 51 patients were evaluated preoperatively and 49 were evaluated 7–12 months postoperatively. The initial body mass index was 51.1 ± 9.2 kg/m², and the final body mass index was 28.2 ± 8.1 kg/m². All patients underwent Roux-en-Y gastric bypass. The 6MWT was performed in a hospital corridor, with patients attempting to cover as much distance as they could, walking back and forth for as long as possible within 6 minutes at their regular pace. The total distance, Borg Scale of perceived exhaustion, modified Borg dyspnea scale for shortness of breath, and physical complaints at the end of the test were recorded. In addition, the heart rate and respiratory frequency were assessed before and after the test.ResultsThe tolerance was good, and no injuries occurred at either evaluation. The patients' mean distance for the 6MWT was 381.9 ± 49.3 m before surgery and 467.8 ± 40.3 m after surgery (p <.0001). Similar results were observed for the other parameters assessed.ConclusionThe 6MWT provided useful information about the functional status of the obese patients undergoing bariatric surgery. A simple, safe, and powerful method to assess functional capacity of severely obese patients, the 6MWT is an objective test that might replace the conventional treadmill test for these types of patients.     

Comparison of Recurrence of Hepatocellular Carcinoma After Resection in Patients with Cirrhosis to Its Occurrence in a Surveilled Cirrhotic Population

The presence of cirrhosis is the only risk factor that is advocated for recurrence of hepatocellular carcinoma (HCC) 2 years after hepatic resection compared with noncirrhotic control subjects; however, data for cohorts of exclusively patients with cirrhosis are lacking. This study was designed to assess risk factors and annual incidence of early (<2 years) and late (>2 years) recurrence after resection of cirrhosis and to compare these findings with those of patients with cirrhosis enrolled in HCC surveillance programs (HCC occurrence). Data from 204 patients with cirrhosis resected for HCC and 150 surveilled for cirrhosis were retrospectively collected and compared using propensity score matching to overcome biases of nonrandomized study. Risk factors for early recurrence (incidence = 21.8%/year) were higher serum alpha-fetoprotein (AFP) levels, poorly differentiated tumor, and presence of microvascular invasion (P < 0.05). Risk factors for both late recurrence (18.4%/year) and HCC occurrence (3.3%/year) were male gender, older age, and higher serum transaminase levels; multiple primary tumors and higher AFP were additional risk factors for late recurrence and HCC occurrence respectively (P < 0.05). After propensity adjustment, resected patients with less than two risk factors for late recurrence showed an annual incidence of HCC (6.2%/year) similar to that of surveilled patients with ≥2 risk factors (5.8%/year; P = 0.898). Early and late recurrence of HCC for patients with cirrhosis after resection have distinct risk factors. Annual incidence of HCC 2 years or more after resection may be similar to that of general patients because the same risk factors are involved; assessment of these characteristics could be useful in tailoring clinical management.     

Upper eyelid reconstruction: a short report of an eyelid defect following a thermal burn

While the principles of eyelid reconstruction are well-established, achieving good functional and aesthetic reconstruction remains challenging. This communication presents a technique that we used on a young patient with an eyelid defect following a thermal burn. The patient was operated on to reconstruct the entire upper eyelid using, as a posterior lamella, a mucochondrial autologous graft taken from the ala of the nose as a tarsus and conjunctiva substitutes that were sutured to the Elevator palpebrae superioris aponeurosis and muscle. On the other hand, to reconstruct the anterior lamella, which consists of skin and muscle, the surgeons used a myocutaneous temporal flap taken from the region immediately lateral to the external canthus of the palpebral region, and which, after being isolated following a drawing of the upper eyelid to be reconstructed, was rotated and then sutured to the posterior lamella using the orbicularis oculi muscle as a pedicle.     

Surgical Treatment of Postinfarction Left Ventricular Free Wall Rupture

Abstract Background: Left ventricular free wall rupture (LVFWR) is still one of the often fatal complications of acute myocardial infarction. Surgical repair is mandatory even with high operative mortality. The optimal surgical technique is controversial since the results depend on type of rupture. We present our mid‐term surgical experience according to the status of the left ventricular tear and type of surgical repair. Methods: From January 1997 to December 2007, 19 consecutive patients with LVFWR were treated at our institution. The mean age was 72 ± 8 ranging from 53 to 81 years; there were eight males and 11 females. According to the intraoperative findings, patients were divided into two groups: group 1 (eight patients), where no macroscopic tear of the LVFW could be detected with blood oozing from infarcted zone (Oozing type LVFWR); and group 2 (11 patients), where a macroscopic defect of the epicardium, with free communication between left ventricular cavity and pericardial space, was identified (Blow‐out type LVFWR). The patch covering and glue technique was applied for group 1 patients, while closure of the ventricular tear either by direct suture or by patch repair was used for group 2 patients. Results: The interval between diagnosis of LVFWR and surgery was 2.9 ± 1.1 hours. However, reevaluation of echocardiographic studies showed an early missed diagnosis of LVFWR in three patients of group 1 and in eight of group 2. Thus, the mean interval between initial signs of rupture and surgery was 9 ± 8 hours and 21 ± 15 hours, respectively, for oozing and blow‐out type rupture. On arrival in the operating room, four patients were on cardiopulmonary resuscitation, while four were in cardiogenic shock. The hospital mortality was 12% (one death) in group 1 and 36% (four deaths) in group 2 mainly due to multiorgan failure. Fourteen patients were discharged with a mean follow‐up of 3.8 ± 3.5 years. During follow‐up, one patient in group 1 died after 7.5 years. No recurrence of free wall rupture or aneurysm formation was demonstrated in all cases. At last follow‐up, all survivors showed excellent clinical results with a preserved left ventricular function. Patients with oozing type LVFWR and patch covering technique repair showed an absence of left ventricular‐restricted motion at the echocardiographic study. Conclusion: In patients with LVFWR, early diagnosis and surgical treatment are crucial for successful outcome when excellent results can be achieved with a simple glued patch covering technique.     

The treatment of asthma in children: inhaled corticosteroids

The evidence that asthma is characterized by extensive inflammation of the airways has warranted the use of inhaled corticosteroid (ICS) in asthma maintenance therapy. Corticosteroid treatment, especially if high or frequent doses are required, is associated with a range of adverse effects including adrenal suppression and impairment in growth and bone metabolism. New corticosteroids are in development, including mometasone furoate, and some of these are predicted to have reduced adverse effects such as the soft steroid ciclesonide. Soft steroids are designed for delivery near to their site of action, to exert their effect and then to undergo controlled and predictable metabolism to inactive metabolites. This review points out the anti-inflammatory effects of corticosteroid in asthmatic airways and the clinical efficacy and safety of ICS in asthmatic children. The development of a soft steroid should help to achieve the aim of improving the therapeutic profile of ICS in asthma and thus alleviate the ongoing problem of poor patient compliance especially in childhood.     

MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle

We have recently reported that MicroRNAs (miR)-221 and miR-222 were up-regulated in human thyroid papillary carcinomas in comparison with the normal thyroid tissue. Bioinformatic analysis proposed the p27(Kip1) protein, a key regulator of cell cycle, as a candidate target for the miR-221/222 cluster. Here, we report that the enforced expression of miR-221 and miR-222 was able to reduce p27(Kip1) protein levels in thyroid carcinoma and HeLa cells in the absence of significant changes in specific p27(Kip1) mRNA levels. This effect is direct as miR-221 and miR-222 negatively regulate the expression of the 3'-untranslated region-based reporter construct from the p27(Kip1) gene, and is dependent on two target sites in this region. Consistent with these results, an enforced expression of the miR-221 and miR-222 induced the thyroid papillary carcinoma cell line (TPC-1) to progress to the S phase of the cell cycle. It is likely that the negative regulation of p27(Kip1) by miR-221 and miR-222 might also have a role in vivo since we report an inverse correlation between miR-221 and miR-222 up-regulation and down-regulation of the p27(Kip1) protein levels in human thyroid papillary carcinomas. Therefore, the data reported here demonstrate that miR-221 and miR-222 are endogenous regulators of p27(Kip1) protein expression, and thereby, the cell cycle.