The effect of bevacizumab on colon anastomotic healing in rats

Purpose

The aim of the study was to investigate the effect of angiogenesis inhibition by bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF) antibody, on the healing process of colonic anastomoses in rats, assessing some specific involved factors. This new agent is used mainly in metastatic colorectal cancer. The angiogenesis plays an important role in both wound healing and metastatic invasion and spread of malignant cells. There has not been any evidence assessing the optimal time for its safe use in operated patients.

Materials and methods

Forty Wistar rats were randomly allocated into four equal groups. A colonic anastomosis was performed in all rats. Half of them received intraoperatively a single dose of bevacizumab 5 mg/body weight and the rest received placebo. The animals were sacrificed on the 7th (Avastin 7th, placebo 7th) and 14th (Avastin 14th, placebo1 4th) postoperative day. The anastomosis was resected and sent for histological study and for tissue biochemical assays (VEGF, endothelin-1 (ET-1), C-reactive protein (CRP), pro-oxidant–antioxidant balance (PAB), carbonylated proteins, hydroxyproline) using specific enzyme-linked immunosorbent assay kits. For statistical analysis, the Mann–Whitney U test was used (of statistical significance when P?<?0.05).

Results

No complication or anastomotic dehiscence was observed. Histology did not reveal statistically significant differences between groups concerning degree of inflammation, fibroblasts, collagen, and fibrosis. Likewise, hydroxyproline levels did not differ. However, some statistically significant differences were found in VEGF, CRP and carbonyl proteins (Avastin 7th vs placebo 7th, placebo 14th vs placebo 7th), ET-1, and PAB (Avastin 14th vs Avastin 7th), which did not finally affect the collagen synthesis marker hydroxyproline, nor did the anastomotic strength.

Conclusions

Bevacizumab, when administered intraoperatively, has no significant effect on colon anastomotic healing in rats despite a transient mild ischemia.     

Outbreak of West Nile virus infection in Greece, 2010

During 2010, an outbreak of West Nile virus infection occurred in Greece. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died. Advanced age and a history of heart disease were independently associated with death, emphasizing the need for prevention of this infection in persons with these risk factors.     

A detailed observation of variations of the facial artery, with emphasis on the superior labial artery

The reconstruction of lip defects through the use of the Abbė flap and other lip flap procedures involves surgical manipulation of one of the major branches of the facial artery, specifically the superior labial artery (SLA). We examined 284 hemifaces derived from 142 formalin fixed cadavers. Observations regarding the distribution patterns of the facial artery were recognized and categorized into five Types, labeled “A” through “E”.Type A (135, 47.5%): facial artery bifurcates into SLA and lateral nasal (the latter gives off inferior and superior alar and ends as angular); Type B (110, 38.7%): similar to Type A, except lateral nasal terminates as superior alar (angular artery is absent); Type C (24, 8.4%): facial artery terminates as SLA; Type D (11, 3.8%): angular artery arises directly from facial arterial trunk rather than as the termination of lateral nasal, with the facial artery ending as superior alar; Type E (4, 1.4%): facial artery terminates as a rudimentary twig without providing any significant branches. Furthermore, we were able to categorize variations within each Type. Sub-Type variations were examined in Types A through C (A: 1–7; B: 1–4; C: 1–3). Our aim was to equip both the anatomist and surgeon with a more thorough understanding of the vasculature of the face, as well as to enable plastic surgeons to have a more confident approach to reconstructive procedures in this region.     

The Ras effector NORE1A is suppressed in follicular thyroid carcinomas with a PAX8-PPARgamma fusion

CONTEXT: The Ras effector NORE1A (RASSF5A) is a putative tumor suppressor and is inactivated in several human cancers. NORE1A has not been studied in thyroid cancer. OBJECTIVE: The objective of this study was to investigate whether NORE1A is involved in follicular thyroid cancer (FTC) development. DESIGN: We analyzed NORE1A expression in 25 FTCs, eight follicular thyroid adenomas, and seven normal thyroid tissues by TaqMan quantitative RT-PCR. The results were evaluated in relation to RASSF1A expression, RAS mutations, and PAX8-PPARgamma fusions assessed in the same material. NORE1A promoter methylation was assessed by the combined bisulfite restriction endonuclease assay. RESULTS: Although the NORE1A mRNA levels of the majority of the tumors were similar to those in the normal controls, the cases harboring a PAX8-PPARgamma translocation (n = 6) exhibited dramatically reduced NORE1A expression (P < 0.001). In contrast, RAS mutations (n = 5) and NORE1A down-regulation were mutually exclusive. A significant reduction in the expression of the NORE1A homolog and the bona fide tumor suppressor gene RASSF1A was observed, but with weak correlation to the respective NORE1A values. No NORE1A promoter methylation was detected in the 32 thyroid tumors analyzed. CONCLUSIONS: Our experiments demonstrate the suppression of NORE1A, a known Ras effector, in PAX8-PPARgamma carrying FTCs.     

A case of hepatocellular carcinoma arising within large focal nodular hyperplasia with review of the literature

INTRODUCTIONFocal nodular hyperplasia(FNH)is a relatively rare benign liver tumor,often asymptomatic and discovered incidentally[1,2].It occurs in both men and women,but shows a predilection for young women.FNH presents as a solitary lesion in70%of the ca…     

Frequency of genetic diseases and health coverage of children requiring admission in a general pediatric clinic of northern Greece

Background

evaluation of thyroid function in neonates born from mothers affected by autoimmune thyroiditis in order to define if a precise follow-up is necessary for these children. The influence of maternal thyroid peroxidase antibody (TPOAb) and L-thyroxine therapy during pregnancy on neonatal thyroid function was also investigated.

Methods

129 neonates were tested for thyroid function by measurement of free thyroxine (FT4) and thyroid stimulating hormone (TSH) in 3^th day, 15^th day and at one month of life. TPOAb were measured in all patients; periodical control of thyroid function were performed until 6 months of life if Ab were positive. Data concerning etiology of maternal hypothyroidism and maternal replacement therapy with L-thyroxine during pregnancy were retrospectively collected.

Results

28% neonates showed at least a mild increase of TSH value at the different determinations. In the majority of them, a spontaneous completely normalisation of TSH value was observed within the first month life. L-thyroxine replacement therapy was started in 3 neonates. TPOAb titer and maternal L-thyroxine replacement therapy were not related to alteration of thyroid hormone function in our study population.

Conclusions

transient mild elevation of serum TSH above the normal reference value for age is frequently observed in the first month of life in infants born from mothers affected by autoimmune thyroiditis. Persistent hyperthyrotropinemia requiring replacement therapy is observed in 2.2% of these neonates. According to our experience, follow-up is recommended in these newborns; the most accurate and not invasive way to carefully monitor these infants after neonatal screening for CH seems to be serum-testing TSH between 2^ndand 4^th week of life.     

The combination of the load/force balance and the frequency/tidal volume can predict weaning outcome

Objective To examine whether an appropriately designed combination of an index of ventilatory endurance and the frequency divided by tidal volume ratio (f/V_T) provides prognostic information for weaning outcome not offered by any index alone.Design and setting Prospective study in a multidisciplinary intensive care unit, university hospital.Patients 124 consecutive mechanically ventilated patients.Interventions We designed an index of ventilatory endurance (load/force balance) calculated as the mean inspiratory airway pressure (P_I) during controlled mechanical ventilation/maximum inspiratory pressure (MIP) [P_I equals the triplicate of mean airway pressure (Paw) displayed by the ventilator] and tested its capacity in predicting weaning outcome at 48 h along with f/V_T and many other indices in 75 consecutive mechanically ventilated patients ready to wean. A stepwise discriminant function analysis was used to test the performance of appropriately designed index combination. Threshold values of indices and their combination were prospectively validated in another group of 45 consecutive patients.Results Stepwise discriminant analysis showed that P_I/MIP and f/V_T were the only indices that remained in the model with the function D = 7.628 × mean Paw/MIP + 0.0158 × f/V_T − 2.374. The cutoff point of D = 0.5 had 94% sensitivity, 67% specificity, and 87% correct classifications. Prospective validation demonstrated similar results. The simplified discriminant function D = 15 × mean Paw/MIP + 0.03 × f/V_T − 5 and the cut-off point of D = 1.0 had 89% sensitivity, 67% specificity, and 85% correct classifications.Conclusions The combination of mean Paw/MIP and f/V_T in a simplified discriminant function is useful in predicting weaning outcome.Electronic Supplementary Material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.     

Muscle activation assessment: effects of method, stimulus number, and joint angle

Activation capacity has traditionally been assessed using the interpolated twitch technique (ITT) and central activation ratio (CAR). However, the quantitative agreement of the two methods and the physiological mechanisms underpinning any possible differences have not been fully elucidated. The aim of this study was to compare and assess the sensitivity of the ITT and CAR to potential errors introduced by (1) evoking inadequate force, by manipulating the number of stimuli, and (2) neglecting differences in series elasticity between conditions, by manipulating joint angle. Ten subjects performed knee extension contractions at 30 degrees and 90 degrees knee-joint angles during which the ITT and CAR methods were applied using 1, 2, 4, and 8 electrical stimuli. Joint angle influenced the ITT outcome with higher values taken at 90 degrees (P < 0.05), while the number of stimuli influenced the CAR outcome with a higher number of stimuli yielding lower values (P < 0.05). For any given joint angle and stimulus number, the CAR method produced higher activation values than the ITT method by 8%-16%. Therefore, in the quantification of voluntary drive with the ITT and CAR methods consideration should be given not only to the number of stimuli applied but also to the effect of series elasticity due to joint-angle differences, since these factors may differently affect the outcome of the calculation, depending on the approach followed.