Canine laryngeal transplantation: preliminary studies and a new heterotopic allotransplantation model

While transplantation of the larynx may eventually be useful in post-laryngectomy reconstruction, three criteria must first be met before human transplants can be attempted: transplant viability must be high, immunosuppression must be safe and effective and functional recovery of the larynx must occur. To study these first two criteria, a total of 11 canine larynx transplants were performed: 3 autografts, 6 orthotopic allografts and 2 heterotopic allografts. The rationale and technical performance of these different transplant procedures are reviewed in detail. Orthotopic transplant recipients received cyclosporin A (CsA) while the heterotopic allograft recipients received RS-61443 and methylprednisolone in addition to CsA. Overall, 9 of 11 of the transplants remained viable. In contrast, all 3 autografted animals developed esophageal-cutaneous fistulas; 2 developed sepsis and were sacrificed on post-operative days (POD) 5 and 28, respectively. The third survived for 91 days and demonstrated a high degree of regeneration in the recurrent and superior laryngeal nerves of the transplant. Orthotopically transplanted dogs also had a high morbidity and perioperative mortality (5 of 6 animals). The single long-term survivor was treated with CsA alone, but developed complete transplant rejection on POD 33. The two heterotopic transplant recipients had no perioperative morbidity and the combination of CsA, RS-61443 and methylprednisolone given these latter animals was effective in the longterm prevention of rejection. One of these heterotopic recipients died of sepsis on POD 68 while the other remained alive and well on POD 168. Our present findings show that currently available microsurgical techniques allow experimental canine laryngeal transplantation to be done with significantly high transplant viability rates. In the dog, CsA alone is inadequate for the long-term prevention of transplant rejection while combined therapy with CsA, RS-61443 and methylprednisolone can provide long-term rejection-free larynx transplant survival. The newly developed heterotopic larynx transplant model allows studies of transplant viability, rejection mechanisms and neural regeneration and functional recovery to be performed with minimal animal morbidity and lowered research costs.Presented at the combined meeting of the Society of Head and Neck Surgeons and the European Organization for Research and Treatment of Cancer (EORTC), Paris, France, 25–28 May, 1994     

Phytoextraction and Phytostabilization of Copper,Zinc, and Iron by Growing Plants in Chahar Gonbad Copper Mining Area,Iran

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Phytoremediation is a promising cleanup technology for heavy-metal-polluted soil. This research examined the...     

Therapeutic hotline: An alternative adjuvant treatment after ear keloid excision using a custom-made methyl methacrylate stent

The efficacy of most pressure devices developed for treatment of ear keloids is limited by the insufficient control of the applied pressure, sometimes causing pain and repeated bleeding with a subsequently increased risk of infections and cosmetic problems. The present study aims to describe the efficacy of the custom-made methyl methacrylate stent in patients that were surgically treated for ear keloids and afterward underwent pressure therapy. The recurrence rate of the ear keloids was evaluated after at least 12 months. Adjuvant treatment with the methyl methacrylate stent resulted in an 83% success rate in our experience with 23 patients that completed the intended therapeutic duration of 18 months. No cases of severe complications were seen during or after the treatment. Furthermore, all the items of the Patient and Observer Scar Assessment Scale resulted in a statistically significant improvement of the scar (p < 0.05). Postoperative pressure therapy with the custom-made methyl methacrylate stent seems efficacious, safe, and is usable for keloids of both the helix and the earlobe.     

Fusarochromanone-induced reactive oxygen species results in activation of JNK cascade and cell death by inhibiting protein phosphatases 2A and 5

Recent studies have shown that fusarochromanone (FC101), a mycotoxin, is cytotoxic in a variety of cell lines. However, the molecular mechanism underlying its cytotoxicity remains elusive. Here we found that FC101 induced cell death in COS7 and HEK293 cells in part by activating JNK pathway. This is evidenced by the findings that inhibition of JNK with SP600125 or expression of dominant negative c-Jun partially prevented FC101-induced cell death. Furthermore, we observed that FC101-activated JNK pathway was attributed to induction of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger and antioxidant, suppressed FC101-induced activation of JNK and cell death. Moreover, we noticed that FC101 inhibited the serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5) in the cells, which was abrogated by NAC. Overexpression of PP2A or PP5 partially prevented FC101-induced activation of JNK and cell death. The results indicate that FC101-induced ROS inhibits PP2A and PP5, leading to activation of JNK pathway and consequently resulting in cell death.     

Identification of Dyslipidemic Patients Attending Primary Care Clinics Using Electronic Medical Record (EMR) Data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) Database

The objective of this study was to define the optimal algorithm to identify patients with dyslipidemia using electronic medical records (EMRs). EMRs of patients attending primary care clinics in St. John’s, Newfoundland and Labrador (NL), Canada during 2009–2010, were studied to determine the best algorithm for identification of dyslipidemia. Six algorithms containing three components, dyslipidemia ICD coding, lipid lowering medication use, and abnormal laboratory lipid levels, were tested against a gold standard, defined as the existence of any of the three criteria. Linear discriminate analysis, and bootstrapping were performed following sensitivity/specificity testing and receiver’s operating curve analysis. Two validating datasets, NL records of 2011–2014, and Canada-wide records of 2010–2012, were used to replicate the results. Relative to the gold standard, combining laboratory data together with lipid lowering medication consumption yielded the highest sensitivity (99.6%), NPV (98.1%), Kappa agreement (0.98), and area under the curve (AUC, 0.998). The linear discriminant analysis for this combination resulted in an error rate of 0.15 and an Eigenvalue of 1.99, and the bootstrapping led to AUC: 0.998, 95% confidence interval: 0.997–0.999, Kappa: 0.99. This algorithm in the first validating dataset yielded a sensitivity of 97%, Negative Predictive Value (NPV) = 83%, Kappa = 0.88, and AUC = 0.98. These figures for the second validating data set were 98%, 93%, 0.95, and 0.99, respectively. Combining laboratory data with lipid lowering medication consumption within the EMR is the best algorithm for detecting dyslipidemia. These results can generate standardized information systems for dyslipidemia and other chronic disease investigations using EMRs.     

Genetic associations in community context: a mixed model approach identifies a functional variant in the <Emphasis Type="Italic">RBP4</Emphasis> gene associated with HDL-C dyslipidemia

Background

The objective of this study was to examine individual and community factors that influence high-density lipoprotein cholesterol (HDL-C) dyslipidemia in Newfoundland and Labrador (NL), a genetically isolated population in Canada with a high prevalence of HDL-C dyslipidemia.

Methods

First, a group of single nucleotide polymorphisms from 10 metabolic trait candidate genes was tested using a multivariate logistic regression model. The significant SNPs were entered into the second phase, where a mixed logistic model incorporated the community disease risk factors together with the individual factors as the fixed part of the model and the geographic region as a random effect.

Results

Analysis of 1489 subjects (26.9% HDL-C dyslipidemia) identified rs3758539, a non-coding variant in the 5’UTR of RBP4, to be associated with HDL-C dyslipidemia (odds ratio?=?1.45, 95% confidence interval?=?1.08–1.97, p?=?0.01). The association remained significant, and the effect size did not change after the incorporation of individual and community risk factors from 17 geographic regions (odds ratio: 1.41, 95% confidence interval?=?1.03–1.93, p?=?0.03) in NL. Besides this variant, sex, BMI, and smoking also showed significant associations with HDL-C dyslipidemia, whereas no role was identified for the community factors.

Conclusions

This study demonstrates the use of community-level data in a genetic association testing. It reports a functional variant in the promoter of RBP4, a gene directly involved in lipoprotein metabolism, to be associated with HDL-C dyslipidemia. These findings indicate that individual factors are the main reason for a higher prevalence of HDL-C dyslipidemia in the NL population.