Recipient intramuscular administration of naked plasmid TGF-β1 attenuates lung graft reperfusion injury

BACKGROUND: Gene therapy may be an effective strategy for modulating lung graft ischemia-reperfusion injury. We investigated whether recipient intramuscular (IM) naked plasmid gene transfer of transforming growth factor beta1-active (TGF-beta1-active) ameliorates lung graft ischemia-reperfusion injury. METHODS: Preliminary studies in F344 rats demonstrated that gastrocnemius muscle transfection of TGF-beta1-active produced muscle and plasma protein expression at 24 and 48 hours after transfection. Recipients (n = 8) received IM injection of naked plasmid-encoding chloramphenicol acetyl transferase (CAT), TGF-beta1-latent or TGF-beta1-active, respectively, at 24 or at 48 hours before left lung transplantation. We did not treat the control group before transplantation (18-hour cold ischemia). Donor lungs were flushed with low-potassium dextran-1% glucose and stored for 18 hours at 4 degrees C. All groups were killed at 24 hours after transplantation. Immediately before killing the animals, we clamped the contralateral right hilum and assessed graft function. We measured wet-to-dry ratio (W/D), myeloperoxidase, pro-inflammatory cytokines (interleukin 1 [IL-1], tumor necrosis factor alpha [TNF-alpha], interferon-gamma [INF-gamma], and IL-2) and performed immunohistochemistry. RESULTS: Arterial oxygenation was greatest in the recipient group transfected with TGF-beta1-active at 24 hours before transplantation compared with CAT, TGF-beta1-latent, and 18-hour cold ischemia groups (p < 0.01). The W/D ratio and myeloperoxidase decreased in both 24- and 48-hour groups, with TGF-beta1-active compared with CAT, and 18-hour cold ischemia groups (W/D, p < 0.02 and p < 0.004, respectively; myeloperoxidase, p < 0.05 and p < 0.01, respectively). All pro-inflammatory cytokines decreased in the 24-hour TGF-beta1-active group compared with CAT, TGF-beta1-latent, 18-hour and 1-hour cold ischemia, and non-treated lung groups (IL-1beta, p < 0.03; TNF-alpha, p < 0.02; IFN-gamma, p < 0.001; IL-2, p < 0.0001). In 24- and 48-hour groups with TGF-beta1-active, immunohistochemistry showed marked staining of Type I and Type II alveolar cells and of macrophages from the apical to the caudal sections of the lung grafts. CONCLUSIONS: Recipient IM administration of naked plasmid encoding TGF-beta1-active before transplantation ameliorates lung isograft reperfusion injury after prolonged ischemia.     

Free flaps for head and neck cancer reconstruction: Does the use of both large cervical vessels as recipient vessels and the employment of end-to-side technique enhance flap survival?

This study specifically investigates whether the use of both large cervical vessels (the external carotid artery and the internal jugular vein) as recipient vessels with end-to-side anastomosis enhance free flap survival in head and neck cancer reconstruction, when compared with the use of other standard smaller neck recipient vessels and end-to-end anastomosis. A total of 84 consecutive patients were included and were divided into two groups (42 in each group) according to the recipient vessels. The overall vessel thrombosis rate was 6% (five of 84 cases) and the overall flap loss rate was 2.4% (two of 84 cases) yielding a flap salvage rate of 60%. Vessel thrombosis occurred in three cases of the smaller vessels group and in two cases of the large cervical vessels group. This was not statistically significant.     

Phenolic Compounds and Bioactivity of Leaves of Mayodendron Igneum Kurz

Four apigenin glycosides were isolated from the ethyl acetate extract of the leaves of Mayodendron igneum Fam.Bignoniaceae. They were identified as apigenin 7-O-glucoside; 6-methoxy apigenin-7-O-glucoside; 6-methoxy apigenin-7-O-rhamnoglucoside and 6-hydroxy apigenin-7-O-rhamnoglucoside. In addition an isoflavone glycoside was isolated, and identified as genistin 5,4‵-methyl ether. Ethanol (80%) extract of Mayodendron igneum leaves exhibited significant anti-inflammatory and analgesic activities. LD₅₀ determination of the extract indicated the safety of the leaves of the plant.     

Minimally invasive approach to management of pituitary adenomas.

Pituitary adenomas are the third most common benign intracranial tumor seen in neurosurgical practice. They represent >or= 15 % of all primary intracranial tumors with 25 % prevalence as reported in autopsy series. Advances in biomedical assays, imaging studies support their diagnosis and tailor their management. The direct endonasal transsphenoidal surgery is the recommended intervention for adenoma resection in more than 95 %. The safety and efficacy of this intervention was enhanced by microsurgery and more recently by the introduction of neuronavigation, assisted endoscopy and intraoperative MRI. Anticipation of clinical, biochemical, radiological and surgical pitfalls by a multidisciplinary team is of paramount importance in improving treatment and preventing potential complications.     

Mortality among married older adults in the suburbs of Beirut: estimates from offspring data

OBJECTIVE: Countries in transition are characterized generally by poor statistical infrastructures and a dearth of vital information. In this study we use offspring data to examine mortality trends in married older men and women through a multipurpose household survey conducted in 2002 in the suburbs of Beirut, Lebanon. The country had been ravaged by war for almost 16 years. METHODS: A random sample of 1520 respondents, with either or both parents surviving their 65th birthday, provided information on 1172 fathers and 1108 mothers. Age- and sex-specific mortality rates per 1000 person-years were estimated. Using log-linear Poisson regression, mortality risk was examined for three birth cohorts: those reaching age 65 before (pre-1975), during (1975-1990) and after (post-1990) hostilities in the country. FINDINGS: A total of 1037 parental deaths were reported, yielding an overall mortality rate of 48.7 per 1000 person-years (51.4 among males and 45.3 among females). Compared to the pre-1975 cohort, older adults reaching age 65 during the war years, 1975-1990, had the highest mortality risk for both males (rate ratio, RR = 1.48, 95% confidence intervals, CI = 1.07-2.04) and females (RR = 1.22, 95% CI = 0.95-1.58). Mortality risk was significantly higher in males than females, a gender differential notably largest in the 1975-1990 cohort. CONCLUSION: This is the first population-based study in Lebanon to quantify patterns of mortality in cohorts of married older adults. The results suggest that the hostilities may have contributed to decreased survival, particularly among males. The approach used in the study presents a viable option for testing in larger surveys and population censuses in countries that lack reliable statistical infrastructures.     

Conversion of some 2(3H)-furanones bearing a pyrazolyl group into other heterocyclic systems with a study of their antiviral activity

3-(1,3-diphenylpyrazol-4-yl-methylene)-5-aryl-2(3H)-furanones 2 were prepared and converted into a variety of heterocyclic systems of synthetic and biological importance. Benzylamine reacted with the furanones 2; the product was found to depend on the reaction conditions. Thus, at room temperature the open-chain N-benzylamides 3 were obtained, whereas under refluxing conditions the 2(3H)-pyrrolones were obtained. Hydrazine hydrate affected ring opening of the furanones to give the corresponding acid hydrazides 5. The latter products were used as key starting materials for the synthesis of pyridazinones 7 and 8, 1,3,4-oxadiazoles 11 and 13 and 1,2,4-triazoles 12 and 14 all bearing pyrazolyl moiety as a side-chain. Evaluation of antiviral activity of selected examples of the compounds obtained was performed using two viruses: HAV and HSV-1. Some of the tested compounds showed promising activities.     

Genetic investigation of 93 families with microphthalmia or posterior microphthalmos

Microphthalmia is a developmental eye defect that is highly variable in severity and in its potential for systemic association. Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next‐generation sequencing multi‐gene panel (i‐panel) as well as whole exome sequencing and molecular karyotyping. A potentially causal mutation was identified in the majority of the cohort with microphthalmia (61%) and posterior microphthalmos (82%). The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1). Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (MYO10 and ZNF219), which we present here as novel candidates for microphthalmia. In addition to revealing novel phenotypic aspects of microphthalmia, this study expands its allelic and locus heterogeneity and highlights the need for expanded testing of patients with this condition.     

Access to oral care before hematopoietic stem cell transplantation: understand to improve

Purpose

Although the relevance of dental intervention before transplant is recognized, many patients are undergoing transplantation without receiving dental care. The objective of this study was to identify the searching profile, access, and use of dental services by candidates to hematopoietic stem cell transplantation (HSCT), and the difficulties faced by those candidates.

Methods

All candidates for an allogeneic HSCT from a bone marrow transplant unit were invited to take part in this research from March 2014 to March 2015. A questionnaire was developed consisting of five sections with questions about personal information, hematologic disease, access to dental services, and history of dental treatment, patient’s preferences, and knowledge.

Results

One hundred and ten candidates for allogeneic HSCT participated in this study. Fifty-five participants received professional oral care in the previous year of interview. The majority of patients (64 %) went to a dentist not linked to transplant staff, and private dental service was the most visited (42 %). To visit a dentist during the previous year was statistically associated with the habit of going to a dentist outside the hospital (p < 0.001), which was statistically associated with the family income (p = 0.001). The main barriers to access to dental treatment were lack of guidance (66 %), apprehension (45 %), and lack of confidence (29 %) in an “external” dentist.

Conclusions

Most of the barriers seem to be associated to lack of confidence and information among patients and professionals, as well as a lack of parameters for scheduling or referrals to dental care, especially for those with a low-socioeconomic background.

     

The prevalence and risk factors of functional dyspepsia in a multiethnic population in the United States

BACKGROUND AND AIMS: The prevalence of functional dyspepsia (FD) in the general population is not known. The aim of this study is to measure the prevalence of FD and its risk factors in a multiethnic volunteer sample of the U.S. population. METHODS: One thousand employees at the Houston VA Medical Center were targeted with a symptom questionnaire asking about upper abdominal symptoms, followed by a request to undergo endsocopy. Dyspepsia was defined by the presence of epigastric pain, fullness, nausea, or vomiting, and FD was defined as dyspepsia in the absence of esophageal erosions, gastric ulcers, or duodenal ulcers or erosions. The presence of dyspepsia and FD was examined in multiple logistic regression analyses. RESULTS: A total of 465 employees completed the relevant questions and of those 203 had endoscopic examination. The age-adjusted prevalence rate of dyspepsia was 31.9 per 100 (95% CI: 26.7-37.1), and 15.8 per 100 (95% CI: 9.6-22.0) if participants with concomitant heartburn or acid regurgitation were excluded. Subjects with dyspepsia were more likely to report smoking, using antacids, aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), and consulting a physician for their symptoms (p < 0.05) than participants without dyspepsia. Most (64.5%) participants with dyspepsia who underwent endoscopy had FD. The age-adjusted prevalence rate of FD was 29.2 per 100 (95% CI: 21.9-36.5), and 15.0 per 100 (6.7-23.3) if subjects with GERD were excluded. Apart from a trend towards association with older age in the multiple regression analysis, there were no significant predictors of FD among participants with dyspepsia. CONCLUSIONS: Most subjects with dyspepsia have FD. The prevalence of FD is high but predictors of FD remain poorly defined.