Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

Background The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration. Supported by The Foundation Fighting Blindness (grant# C-NC02-798-0078), The Faculty of Medicine, University of Lund, The Swedish Research Council, The Princess Margaretas Foundation for Blind Children, The 2nd ONCE International Award for New Technologies for the Blind.     

Retinal function and PKC alpha expression after focal laser photocoagulation

Purpose

To examine the effects of focal laser photocoagulation on general and local retinal function and to relate electrophysiological findings with changes in protein kinase C (PKC) alpha expression.

Methods

Twelve rabbits were treated with 70 spots of laser photocoagulation in the central cone-rich retina. The operated eyes were investigated with electroretinography (full-field ERG and multifocal electroretinography, mfERG) preoperatively and at 1, 3, and 5 weeks after surgery. The expression of PKC alpha was examined at all three time points using immunohistochemistry, and PKC alpha mRNA levels were quantified using real-time polymerase chain reaction (PCR). Immunohistochemistry for glial fibrillary acidic protein (GFAP) and hematoxylin and eosin staining was employed to monitor the extent and dynamics of the morphological response.

Results

The full-field ERG revealed a significant increase in b-wave amplitudes derived from the isolated rod response (blue light) at all three time points after surgery (p?Conclusions Focal laser treatment in the rabbit eye induces local and wide-spread alterations in both rod- and cone-mediated retinal function in the form of supernormal b-wave amplitudes in the full-field ERG and increased latency in the mfERG. The electrophysiological abnormalities are accompanied by a progressive down-regulation of the PKC alpha isoenzyme in rod bipolar cells, reaching far beyond the treated area. PKC alpha is down-regulated directly by impaired protein synthesis, and also possibly indirectly by protein consumption related to GFAP up-regulation. The results indicate that focal laser photocoagulation interferes with PKC-alpha-mediated inhibitory regulation of inner retinal signal transmission.     

Screening for Alcohol Dependence and Abuse in Women: Description, Validation, and Psychometric Properties of a New Screening Instrument, SWAG, in a Population Study

In this study, we have evaluated the use of a screening instrument in the first phase of a population study of female alcoholism and alcohol problems. The instrument, called SWAG (Screening, Women, and Alcohol in Göteborg), is a 13-item questionnaire. It includes a modified version of CAGE. The study sample consisted of 3,130 women. Of these, a stratified sample of 479 were invited for interview. Validation was done against interview-based clinical diagnosis according to DSM-III-R (alcohol dependence and abuse), with additional use of medical record information. SWAG had similar sensitivity and specificity used on a population sample, as previously has been found for alcohol problem screening instruments tested in clinical settings. Positive predictive value, rarely reported in studies of other alcohol screening instruments, was 40 to 50%. With logistic regression, we developed a promising set of criteria, called SWAG-L, that had similar sensitivity, specificity, and positive predictive value as the longer version SWAG-1, at the same time it consisted of only four items. CAGE had considerably lower sensitivity than SWAG. SWAG can, so far, be recommended for use in epidemiological studies. It may also prove valuable in clinical settings, although that requires a different scoring method. The question, "I have/have had alcohol problems" was the single item that best predicted alcohol dependence and abuse.     

Costs of COPD in Sweden according to disease severity

OBJECTIVES: COPD is a common and disabling disease that entails high costs for society. The objectives of this study were to measure the societal costs of COPD in Sweden, and to examine the relationship between severity of illness and costs. METHODS: The costs of COPD were examined using a well-defined and representative cohort of subjects with mild, moderate, and severe COPD. Regular telephone interviews regarding resource utilization were made to a cohort of 212 subjects with COPD derived from studies of the general population in Northern Sweden. RESULTS: The annual per capita cost for COPD in Swedish crowns (SEK) was estimated at SEK 13,418 (1,284 US dollars (USD); 1,448 euros (EUR). The direct and indirect costs were SEK 5,592 (42%) and SEK 7,828 (58%), respectively. A highly significant relationship was found between severity of disease and costs. Costs for severe disease were 3 times as high as costs for moderate disease and > 10 times as high as for mild disease. Large individual variations in the level of costs were found. CONCLUSION: Assuming that the prevalence and treatment patterns are representative of Sweden as a whole, the total costs of COPD to society in 1999 were estimated at SEK 9.1 billion (USD 871 million; EUR 982 million). Subjects with mild disease (83%) accounted for 29%, while subjects with moderate disease (13%) accounted for 41% of the total costs. The subjects with severe disease (4%) accounted for the remainder (30%). Prevention, early diagnosis, and postponement of disease progression should have large monetary and policy implications.     

Atrial fibrillation signal organization predicts sinus rhythm maintenance in patients undergoing cardioversion of atrial fibrillation.

AIMS: Electrical remodelling is believed to influence the outcome following cardioversion of patients with persistent atrial fibrillation (AF). However, the results in clinical studies are conflicting. We assessed the hypothesis that non-invasively obtained atrial fibrillatory organization can be used as a predictor of sinus rhythm (SR) maintenance. METHODS AND RESULTS: Fifty-four patients (37 men, age 67+/-11) with persistent AF (median duration 3 months, 1 day to 18 months), without anti-arrhythmic drug treatment, referred for cardioversion were studied. Assessment of the atrial harmonic decay was made by time-frequency analysis of the ECG. At 1-month follow-up, 30 patients had relapsed into AF. The mean harmonic decay at inclusion of those relapsing into AF was 1.5+/-0.3 compared with 1.1+/-0.3 among those maintaining SR (P=0.0004). Using a cut-off value of harmonic decay 相似文献   

Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension

Aims/hypothesis Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by -tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats.Methods Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL--tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes.Results Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with -tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by -tocopherol treatment.Conclusions/interpretation We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.Abbreviations ROS Reactive oxygen species - TBARS thiobarbituric acids reactive substances - NO nitric oxide - STZ streptozotocin     

The Moxus Modular metabolic system evaluated with two sensors for ventilation against the Douglas bag method

This study evaluated the Moxus metabolic system with the Douglas bag method (DBM) as criterion. Reliability and validity were investigated in a wide range of ventilation and oxygen uptake and two sensors for determining ventilation were included. Thirteen well-trained athletes participated in one pre-test and four tests for data collection, exercising on a cycle ergometer at five submaximal powers (50–263 W) and at $ V{\text{O}}_{{2{ \hbox{max} }}} $ . Gas exchange variables were measured simultaneously using a serial setup with data collected on different days in an order randomized between Moxus with pneumotachometer (MP) and turbine flowmeter (MT) sensors for ventilation. Reliability with both sensors was comparable to the DBM. Average CV (%) of all exercise intensities were with MP: 3.0 ± 1.3 for VO₂, 3.8 ± 1.5 for VCO₂, 3.1 ± 1.2 for the respiratory exchange ratio (RER) and 4.2 ± 0.8 for V _E. The corresponding values with MT were: 2.7 ± 0.3 for VO₂, 4.7 ± 0.4 for VCO₂, 3.3 ± 0.9 for RER and 4.8 ± 1.4 for V _E. Validity was acceptable except for small differences related to the determination of ventilation. The relative differences in relation to DBM at the powers including $ V{\text{O}}_{2\hbox{max} } $ were similar for both sensors with the ranges being: +4 to ?2 % for V _E, +5 to ?3 % for VO₂ and +5 to ?4 % for VCO₂ while RER did not differ at any power. The Moxus metabolic system shows high and adequate reliability and reasonable validity over a wide measurement range. At a few exercise levels, V _E differed slightly from DBM, resulting in concomitant changes in VO₂ and VCO₂.     

In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1

Molecular Imaging and Biology - In vivo imaging of programmed death ligand 1 (PD-L1) during immunotherapy could potentially monitor changing PD-L1 expression and PD-L1 expression heterogeneity...