Enhancement of sciatic nerve regeneration after vascular endothelial growth factor (VEGF) gene therapy

F. R. Pereira Lopes, B. C. G. Lisboa, F. Frattini, F. M. Almeida, M. A. Tomaz, P. K. Matsumoto, F. Langone, S. Lora, P. A. Melo, R. Borojevic, S. W. Han and A. M. B. Martinez (2011) Neuropathology and Applied Neurobiology 37, 600–612 Enhancement of sciatic nerve regeneration after vascular endothelial growth factor (VEGF) gene therapy Aims: Recent studies have emphasized the beneficial effects of the vascular endothelial growth factor (VEGF) on neurone survival and Schwann cell proliferation. VEGF is a potent angiogenic factor, and angiogenesis has long been recognized as an important and necessary step during tissue repair. Here, we investigated the effects of VEGF on sciatic nerve regeneration. Methods: Using light and electron microscopy, we evaluated sciatic nerve regeneration after transection and VEGF gene therapy. We examined the survival of the neurones in the dorsal root ganglia and in lumbar 4 segment of spinal cord. We also evaluated the functional recovery using the sciatic functional index and gastrocnemius muscle weight. In addition, we evaluated the VEGF expression by immunohistochemistry. Results: Fluorescein isothiocyanate‐dextran (FITC‐dextran) fluorescence of nerves and muscles revealed intense staining in the VEGF‐treated group. Quantitative analysis showed that the numbers of myelinated fibres and blood vessels were significantly higher in VEGF‐treated animals. VEGF also increased the survival of neurone cell bodies in dorsal root ganglia and in spinal cord. The sciatic functional index and gastrocnemius muscle weight reached significantly higher values in VEGF‐treated animals. Conclusion: We demonstrate a positive relationship between increased vascularization and enhanced nerve regeneration, indicating that VEGF administration can support and enhance the growth of regenerating nerve fibres, probably through a combination of angiogenic, neurotrophic and neuroprotective effects.     

Colecistectomía laparoscópica en régimen de cirugía mayor ambulatoria en un hospital comarcal: resultados iniciales de una serie de 110 casos

IntroductionThe aim of our study was to analyze the reliability of laparoscopic cholecystectomy (LC) in an Ambulatory Surgery unit, in order to encourage its use and achieve better management of health resources.Material and methodRetrospective study of 110 patients operated on for LC between September 2004 and November 2008. The selection criteria were: absence of prior supramesocolic abdominal surgery, no previous admission for acute cholecystitis, absence of stones in the bile ducts and normal liver function tests, no intake of oral anticoagulants or antiplatelet agents and ASA I-II. All patients were operated using a previously established Major Ambulatory Surgery (MAS) protocol.ResultsThe patients included 81 women and 29 men, with a mean age of 51.03 years (range 24–77), of which 57 had a medical and / or surgical history.The overall morbidity was 6.36% with a mortality of 0%. The conversion rate was 0.9%. A total of 87 patients (79.1%) were discharged at 6 h after surgery, thus fulfilling the criteria of the MAS system. The mean overall hospital stay was 1.49 days (median 0). The reoperation rate WAS 1.81% and the rate of readmission after discharge was0.9%.ConclusionsThe performance of outpatient laparoscopic cholecystectomy is feasible and safe. It should be integrated into the activities of Major Ambulatory Surgery, ensuring careful selection of patients and interest by surgeon who performs it.     

Assessment of complement C4 gene copy number using the paralog ratio test

The complement C4 locus is in the class III region of the MHC, and exhibits copy number variation. Complement C4 null alleles have shown association with a number of diseases including systemic lupus erythematosus (SLE). However, most studies to date have used protein immunophenotyping and not direct interrogation of the genome to determine C4 null allele status. Moreover, a lack of accurate C4 gene copy number (GCN) estimation and tight linkage disequilibrium across the disease‐associated MHC haplotypes has confounded attempts to establish whether or not these associations are causal. We have therefore developed a high throughput paralog ratio test (PRT) in association with two restriction enzyme digest variant ratio tests (REDVRs) to determine total C4 GCN, C4A GCN, and C4B GCN. In the densely genotyped CEU cohort we show that this method is accurate and reproducible when compared to gold standard Southern blot copy number estimation with a discrepancy rate of 9%. We find a broad range of C4 GCNs in the CEU and the 1958 British Birth Cohort populations under study. In addition, SNP‐C4 CNV analyses show only moderate levels of correlation and therefore do not support the use of SNP genotypes as proxies for complement C4 GCN. Hum Mutat 31:1–9, 2010. © 2010 Wiley‐Liss, Inc.     

Clinical outcome of low-risk differentiated thyroid cancer patients after radioiodine remnant ablation and recombinant human thyroid-stimulating hormone preparation

AimRecombinant human thyroid-stimulating hormone (rhTSH) has been approved in Europe as a preparation tool for radioiodine ablation of post-surgical thyroid remnants in patients with low-risk differentiated thyroid cancer (DTC). Published studies report that, both thyroid hormone withdrawal and rhTSH preparation result in similar rates of successful remnant ablation, but few studies have determined the effectiveness of rhTSH preparation on disease recurrence. We sought to determine the clinical outcome, considering both ablation success and disease recurrence, of low-risk DTC patients who underwent ¹³¹I ablation.Materials and methodsThis retrospective study describes the clinical outcome of 100 patients treated with ¹³¹I remnant ablation after preparation with rhTSH. After ablation, patients were classified as in complete remission, as having no evidence of persistent disease, or as having clinical recurrence on the basis of a subsequent diagnostic whole body scan with ¹³¹I, stimulated thyroglobulin and cross-sectional imaging studies.ResultsOverall assessment of ablation success was verified and obtained in 75% of patients (75/100). Considering only patients who underwent a diagnostic whole body scan and stimulated thyroglobulin without interfering anti-thyroglobulin antibody, complete ablation was obtained in 96% of patients (75/78). After a follow-up of about 4 years, 78 patients are in complete remission: 75 with initial ablation success and three who achieved a complete remission during subsequent follow-up. Among the remaining 22 patients, 21 have no clinical evidence of disease (NCED), indicating the inability to verify the complete remission or to detect residual disease, as in patients with positive thyroglobulin antibody, whereas one has persistent disease demonstrated only by stimulated thyroglobulin. No recurrences were observed. Of four patients initially classified as having persistent disease, one obtained a complete remission and two are now considered NCED.ConclusionOur data confirm the favourable outcome, with low rates of recurrence and persistent disease, of patients with low-risk DTC who underwent ¹³¹I ablation after rhTSH. Moreover, our results compare favourably with those reported in the literature in patients prepared with rhTSH, but also in patients prepared with hormone withdrawal.     

An evaluation of a computer‐imaging program to prepare women for chemotherapy‐related alopecia

Objective: This study was conducted to evaluate a computer program named Help with Adjustment to Alopecia by Image Recovery (HAAIR) that was developed to provide educational support and reduce distress in women with hair loss following chemotherapy. Methods: Forty‐five women who had been diagnosed with cancer and anticipated alopecia following treatment were randomly assigned to either the Imagining group (IG) or Standardized Care group (SCG). Patients in the IG used a computer‐imaging program that created the patient's image on a screen to simulate baldness and use of wigs whereas patients in the SCG were directed to a resource room at the Cancer Center established for women with chemotherapy‐related alopecia. Assessment data using the Brief Symptom Inventory, Importance of Hair Questionnaire, and the Brief Cope were completed at baseline (T1), before chemotherapy and hair loss, following hair loss (T2), and 3 months follow‐up (T3). Results: All women were able to successfully use the touch screen computerized‐imaging program and reported that using the computer was a positive, helpful experience, thus establishing acceptability and usability. Women in both the IG and the SCG group showed significantly lower hair loss distress scores at T2 after hair loss than at T1 with T3 distress scores increasing in the SCG and decreasing in the IG. Those with avoidance coping reported more distress. Conclusions: This evaluation demonstrates that the HAAIR program is a patient‐endorsed educational and supportive complement to care for women facing chemotherapy‐related alopecia. Copyright © 2009 John Wiley & Sons, Ltd.     

Differential expression of anterior gradient gene AGR2 in prostate cancer

Background

The post-translational modification of proteins, including glycosylation, differs between normal and tumor cells. The UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferases (GalNAc-Tases) family of enzymes regulates the initial steps of mucin O-glycosylation and is responsible for the altered glycosylation state observed in cancer cells. Recently it was found that GalNAc-T14 mRNA is heterogeneously expressed in breast carcinomas compared to normal tissue, however the expression profile of GalNAc-T14 protein in breast carcinomas compared to normal tissue is still unknown. In this study, we assessed the expression profile of GalNAc-T14 protein in malignant and non-malignant breast tissues by immunohistochemistry to evaluate whether GalNAc-T14 might be a potential biomarker for breast cancer.

Methods

In formalin-fixed tissues, the expression level of GalNAc-T14 protein was evaluated by immunohistochemistry assay in breast tissues. Expression profiles were assessed in normal tissues, benign fibroadenomas and several types of carcinomas.

Results

Our results showed that GalNAc-T14 was heterogeneously expressed in breast carcinomas compared to non-malignant tissue. GalNAc-T14 expression was observed in 47/56 (83.9%) carcinoma samples, 7/48 (14.6%) non-malignant breast tissue samples. GalNAc-T14 expression level was associated with histological grade. For this enzyme a significant association with invasive ductal type, mucinous adenocarcinoma and ductal carcinoma in situ (DCIS) type was found.

Conclusion

Our results provide evidence that GalNAc-T14 may be a potential biomarker for breast cancer by immunohistochemistry. GalNAc-T14 expression level was associated with histological grade. GalNAc-T14 expression can provide new insights about breast cancer glycobiology.     

Beta-binomial/Poisson regression models for repeated bivariate counts

We analyze data obtained from a study designed to evaluate training effects on the performance of certain motor activities of Parkinson's disease patients. Maximum likelihood methods were used to fit beta-binomial/Poisson regression models tailored to evaluate the effects of training on the numbers of attempted and successful specified manual movements in 1 min periods, controlling for disease stage and use of the preferred hand. We extend models previously considered by other authors in univariate settings to account for the repeated measures nature of the data. The results suggest that the expected number of attempts and successes increase with training, except for patients with advanced stages of the disease using the non-preferred hand.