Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine

A 12‐day course of high‐dose tacrolimus induces tolerance of major histocompatibility complex–mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart–lung cotransplantation using the same induction protocol. Hearts (n = 3), heart–kidneys (n = 3), lungs (n = 6), and hearts–lungs (n = 3) were transplanted into fully major histocompatibility complex–mismatched recipients treated with high‐dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart–kidney recipients and five of six lung recipients demonstrated long‐term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor‐specific unresponsiveness by cell‐mediated lympholysis/mixed‐lymphocyte reaction. In contrast, heart–lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms.     

Preventing Futile Liver Resection: A Risk-Based Approach to Surgical Selection in Major Hepatectomy for Colorectal Cancer

Annals of Surgical Oncology - Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early...     

Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

Background: Longevinex^® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D₃ and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.     

Experiences of community and parental violence among HIV-positive young racial/ethnic minority men who have sex with men

Adolescents and young adults (ages 13–24) in the USA are frequently exposed to violence in their community and home. While studies have examined the prevalence and impact of violence exposure among adolescents, there is a lack of data focusing specifically on adolescent men of color who have sex with men. Eight demonstration sites funded through a Special Projects of National Significance (SPNS) Initiative recruited 363 HIV-positive racial/ethnic minority young men who have sex with men (YMSM) for a longitudinal study between 2006 and 2009. Over two-thirds of participants (83.8%) had witnessed community violence, 55.1% in the prior three months. Witnessing violence committed with a deadly weapon was significantly associated with being African-American, having ever used drugs, and drinking alcohol in the prior two weeks. Fear of violence in the community was significantly associated with depressive symptomatology, having less than a high school degree, not possessing health insurance, and site of enrollment. Having been emotionally or physically abused by a parent or caretaker was significantly associated with depressive symptomatology, attempting suicide, site of enrollment, and increased age. Witnessing violence with a deadly weapon was significantly associated with alcohol and drug use but not with high-risk sexual behaviors. As this was one of the first studies on the prevalence and correlates of violence exposure among racial/ethnic minority YMSM living with HIV, the findings can be used to inform the development of culturally appropriate resilience-focused interventions to address the aftereffects of violence exposures and help develop social support systems outside of the family.     

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011

Objectives

It is currently unknown whether chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, is transmissible to humans. Reported on here are the behavioural risk factors and health conditions associated with a six-year follow-up of a known point-source exposure to a CWD infected deer in an Upstate New York community.

Study design

Longitudinal.

Methods

The Oneida County Chronic Wasting Disease Surveillance Project was launched in 2005 in response to a point-source exposure to a CWD infected deer at a March 2005 Sportsmen's feast in Upstate New York. Eighty-one exposed individuals participated in the 2005 baseline data collection, and were sent follow-up questionnaires following each deer hunting season between 2005 and 2011.

Results

Over a six year period, participants reported a reduction in overall venison consumption. Participants reported no significant changes in health conditions, although several conditions (vision loss, heart disease, type 2 diabetes, weight changes, hypertension, and arthritis), were significantly associated with age.

Conclusions

To this day, this incident remains the only known large-scale point-source exposure to a CWD infected deer. Prion diseases can incubate for multiple decades before the manifestation of clinical symptoms; thus, continued surveillance of this exposed study population represents a unique opportunity to assess the risk of CWD transmission to humans. This project is uniquely situated to provide the first epidemiological evidence of CWD transmission to humans, should it occur.