Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence

Background: The purpose of this study was to examine relationships between genetic markers of central serotonin (5‐HT) and dopamine function, and risk for post‐treatment relapse, in a sample of alcohol‐dependent patients. Methods: The study included 154 patients from addiction treatment programs in Poland, who met DSM‐IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow‐up) while controlling for baseline measures. Results: Of 154 eligible patients, 123 (80%) completed follow‐up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post‐treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger. Conclusions: The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.     

Spontaneous recanalization of a completely occluded saphenous vein graft two months following acute myocardial infarction with persistent one year patency

Acute myocardial infarction resulting from saphenous vein graft occlusion occurs not infrequently in patients who have undergone coronary artery bypass graft surgery. In this case report, we present a novel case of spontaneous recanalization of a thrombotic graft occlusion in a patient who presented with a subacute myocardial infarction. The patient was treated medically with aspirin as the only anti-platelet agent. Interestingly, he presented 2 months later with new onset angina. Coronary angiography demonstrated complete resolution of thrombus but a severe focal stenosis in the distal anastomoses. Following drug eluting stent placement, a favorable clinical course has ensued and patency confirmed on follow up angiography at 1 year.     

75 MHz ultrasound biomicroscopy of anterior segment of eye

Very high frequency ultrasound (35-50 MHz) has had a significant impact upon clinical imaging of the anterior segment of the eye, offering an axial resolution as small as 30 microm. Higher frequencies, while potentially offering even finer resolution, are more affected by absorption in ocular tissues and even in the fluid coupling medium. Our aim was to develop and apply improved transducer technology utilizing frequencies beyond those routinely used for ultrasound biomicroscopy of the eye. A 75-MHz lithium niobate transducer with 2 mm aperture and 6 mm focal length was fabricated. We scanned the ciliary body and cornea of a human eye six years post-LASIK. Spectral parameter images were produced from the midband fit to local calibrated power spectra. Images were compared with those produced using a 35 MHz lithium niobate transducer of similar fractional bandwidth and focal ratio. The 75-MHz transducer was found to have a fractional bandwidth (-6 dB) of 61%. Images of the post-LASIK cornea showed higher stromal backscatter at 75 MHz than at 35 MHz. The improved lateral resolution resulted in better visualization of discontinuities in Bowman's layer, indicative of microfolds or breaks occurring at the time of surgery. The LASIK surface was evident as a discontinuity in stromal backscatter between the stromal component of the flap and the residual stroma. The iris and ciliary body were visualized despite attenuation by the overlying sclera. Very high frequency ultrasound imaging of the anterior segment of the eye has been restricted to the 35-50 MHz band for over a decade. We showed that higher frequencies can be used in vivo to image the cornea and anterior segment. This improvement in resolution and high sensitivity to backscatter from the corneal stroma will provide benefits in clinical diagnostic imaging of the anterior segment.     

Efficacy and mechanism of orthotic devices to unload metatarsal heads in people with diabetes and a history of plantar ulcers

BACKGROUND AND PURPOSE: Total-contact inserts (TCIs) and metatarsal pads (MPs) frequently are prescribed to reduce excessive plantar stresses to help prevent skin breakdown in people with diabetes mellitus (DM) and peripheral neuropathy. The first purpose of this study was to determine the effect of a TCI and an MP on metatarsal head peak plantar pressures (PPP) and pressure-time integrals (PTI). The second purpose of this study was to determine a possible mechanism of pressure reduction by measuring contact area and loaded soft-tissue thickness (STT) under the metatarsal heads and second metatarsal shaft. SUBJECTS: Twenty subjects (12 men and 8 women; age [mean+/-SD]=57+/-9 years) with DM (duration [mean+/-SD]=16+/-11 years), peripheral neuropathy, and a history of plantar ulcers participated. METHODS: A repeated-measures research design was used, and outcome measures are reported for 3 footwear conditions: shoe, shoe with TCI, and shoe with TCI and MP. In-shoe plantar pressures were collected during walking and during spiral x-ray computed tomography (SXCT). The STT and identification of the pressure sensor and location of the MP in relationship to the metatarsal heads were determined by use of SXCT. RESULTS: The PPP and the PTI were 16% to 24% lower at the metatarsal heads in the TCI condition than in the shoe condition. The PPP and the PTI decreased an additional 15% to 28% (for a total reduction of 29% to 47%) with the addition of the MP. The contact area increased 27% with the TCI but not with the MP. The STT did not increase under the metatarsal heads in the TCI condition (compared with the shoe condition) but did increase 8% to 22% at metatarsal heads 2 to 5 with the addition of the MP. The PPP increased substantially (308%) and the STT decreased 14% under the shaft of the second metatarsal with the addition of the MP to the TCI-plus-shoe condition. DISCUSSION AND CONCLUSION: The TCI and the MP caused substantial and additive reductions of pressures under the metatarsal heads. The TCI reduces excessive pressures at the metatarsal heads by increasing the contact area of weight-bearing forces. Conversely, the MP acts by compressing the soft tissues proximal to the metatarsal heads and relieving compression at the metatarsal heads. These findings can assist in the design of effective orthotic devices to relieve excessive plantar stresses that contribute to skin breakdown and subsequent amputation in people with DM and peripheral neuropathy.     

Comparison of African-American patients with systolic heart failure versus preserved ejection fraction

Evidence exists for race-specific differences in the cause and natural history of heart failure (HF). These differences may have important treatment implications, but relatively limited data on African-Americans exist. A cohort of 89 African-American patients admitted to an urban teaching hospital with diagnoses of HF was examined. Most patients had systolic HF (71%), and the remainder had HF with preserved ejection fractions (EFs). Patients with HF with preserved EFs tended to be generally older (67 vs 57 years, p = 0.01) and were more likely to be women (69% vs 42%, p = 0.02). There were no significant differences between patients with systolic HF and those with HF with preserved EFs in the prevalence of coronary artery disease (23%), diabetes mellitus (44%), or chronic obstructive pulmonary disease (38%). Gastrointestinal bleeding and anemia were significant contributors to admission in patients with preserved EFs, with baseline hematocrits being significantly lower (34.9 vs 38.3, p = 0.01). On discharge, patients with HF with preserved EFs were less likely to be prescribed angiotensin-converting enzyme inhibitors than patients with systolic HF (65% vs 83%, p = 0.08) or diuretics (58% vs 82.%, p = 0.03). In conclusion, differences exist in African-American patients who present with HF; optimal therapeutic approaches will require a better understanding of their underlying pathophysiology.     

Quantitative trait loci modifying cardiac atrial septal morphology and risk of patent foramen ovale in the mouse

Atrial septal defect (ASD) is a common congenital heart disease (CHD) occurring in 5 to 7 per 10,000 live births. Mutations in 5 human genes (NKX2.5, TBX5, GATA4, MYHC, ACTC) are known to cause dominant ASD, but these account for a minority of cases. Human and mouse data suggest that ASD exists in an anatomical continuum with milder septal variants patent foramen ovale (PFO) and atrial septal aneurysm, strongly associated with ischemic stroke and migraine. We have previously shown in inbred mice that the incidence of PFO strongly correlates with length of the interatrial septum primum, defining a quantitative trait underlying PFO risk. To better understand genetic causation of atrial septal abnormalities, we mapped quantitative trait loci (QTL) influencing septal morphology using mouse strains (QSi5 and 129T2/SvEms) maximally informative for PFO incidence and 3 quantitative septal anatomical traits including septum primum length. [QSi5x129T2/SvEms]F2 intercross animals (n=1437) were phenotyped and a whole genome scan performed at an average 17-cM interval. Statistical methodology scoring PFO as a binary phenotype was developed as a confirmatory mapping technique. We mapped 7 significant and 6 suggestive QTL modifying quantitative phenotypes, with 4 supported by binary analysis. Quantitative traits, although strongly associated with PFO (P<0.001), correlated poorly with each other and in all but 1 case QTL for different traits were nonoverlapping. Thus, multiple anatomical processes under separate genetic control contribute to risk of PFO. Our findings demonstrate the feasibility of modeling the genetic basis of common CHD using animal genetic and genomic technologies.     

Reduction in Adhesive Small-Bowel Obstruction by Seprafilm® Adhesion Barrier After Intestinal Resection

Introduction Although Seprafilm^? has been demonstrated to reduce adhesion formation, it is not known whether its usage would translate into a reduction in adhesive small-bowel obstruction. Methods This was a prospective, randomized, multicenter, multinational, single-blind, controlled study. This report focuses on those patients who underwent intestinal resection (n = 1,701). Before closure of the abdomen, patients were randomized to receive Seprafilm^? or no treatment. Seprafilm^? was applied to adhesiogenic tissues throughout the abdomen. The incidence and type of bowel obstruction was compared between the two groups. Time to first adhesive small-bowel obstruction was compared during the course of the study by using survival analysis methods. The mean follow-up time for the occurrence of adhesive small-bowel obstruction was 3.5 years. Results There was no difference between the treatment and control group in overall rate of bowel obstruction. The incidence of adhesive small-bowel obstruction requiring reoperation was significantly lower for Seprafilm^? patients compared with no-treatment patients: 1.8 vs. 3.4 percent (P < 0.05). This finding represents an absolute reduction in adhesive small-bowel obstruction requiring reoperation of 1.6 percent and a relative reduction of 47 percent. In addition, a stepwise multivariate analysis indicated that the use of Seprafilm^? was the only predictive factor for reducing adhesive small-bowel obstruction requiring reoperation. In both groups, 50 percent of first adhesive small-bowel obstruction episodes occurred within 6 months after the initial surgery with nearly 30 percent occurring within the first 30 days. Additionally no first adhesive small-bowel obstruction events were reported in Years 4 and 5 of follow-up. Conclusions The overall bowel obstruction rate was unchanged; however, adhesive small-bowel obstruction requiring reoperation was significantly reduced by the use of Seprafilm^?, which was the only factor that predicted this outcome. Supported by a grant from Genzyme Corporation, which manufacturers Seprafilm. Read at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 10 to 13, 2004.     

Genetics education in the nursing profession: literature review

AIM: This paper reports a literature review exploring genetics education for nursing professionals. The aim was to contribute to the debate about the future direction of such education. BACKGROUND: Advances in genetics science and technology have profound implications for health care and the growing importance and relevance of genetics for everyday nursing practice is increasingly recognized. METHOD: A search was conducted in February 2005 using the CINAHL and Google Scholar databases and the keywords nurse, midwife, health visitor, education and genetics. Papers were included if they were published in English between 1994 and 2005 and included empirical data about genetics education in nursing. In addition, attempts were made to access the grey literature, with requests for information on research, for example, to members of the Association of Genetic Nurses and Counsellors and searches of relevant websites. FINDINGS: Agreement on the relevance of genetics for nursing practice is extensive. Empirical evidence of the learning needs of practitioners highlights widespread deficits in knowledge and skills, and low confidence levels. Provision of nursing education in genetics is patchy and insubstantial across a number of countries, further hampered by lack of strategic development. Significant progress has been made in the identification of learning outcomes for nurses. Research on the delivery of genetics education is limited, but the role of skills-based training, use of clinical scenarios, and importance of assessment have all been identified as factors that can promote learning. CONCLUSION: Whilst areas of good performance were revealed, many studies identified gaps in professional competence and/or education. New initiatives are underway to support genetics education and its integration into professional practice, but further research is needed on the most effective forms of educational delivery, and an international collaborative approach to this should be considered.