bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental differences in H2O2‐induced oligodendrocyte cell death: role of glutathione, mitogen‐activated protein kinases and caspase 3
Authors: Fragoso Gabriela , Martínez‐Bermúdez Ana Katherine , Liu Hsueh‐Ning , Khorchid Amani , Chemtob Sylvain , Mushynski Walter E. , Almazan Guillermina
Published: July 2004

The molecular mechanisms underlying H2O2‐induced toxicity were characterized in rat oligodendrocyte cultures. While progenitor cells were more sensitive than mature oligodendrocytes to H2O2, the antioxidant, N‐acetyl‐l‐cysteine, blocked toxicity at both stages of development. Differentiated oligodendrocytes contained more glutathione than did progenitors and were less susceptible to decreases in glutathione concentration induced by H2O2 stress. As free radicals have been considered to serve as second messengers, we examined the effect of H2O2 on activation of the mitogen‐activated protein kinases (MAPK), extracellular signal‐regulated kinases (ERK) 1/2 and p38. H2O2 caused a time‐ and concentration‐dependent increase in MAPK phosphorylation, an effect that was totally blocked by N‐acetyl‐l‐cysteine. Further exploration of potential mechanisms involved in oligodendrocyte cell death showed that H2O2 treatment caused DNA condensation and fragmentation at both stages of development, whereas caspase 3 activation and poly (ADP‐ribose) polymerase cleavage were significantly increased only in oligodendrocyte progenitors. The pan‐caspase inhibitor, benzyloxycarbonyl‐Val‐Ala‐Asp fluoromethyl ketone, blocked DNA fragmentation in progenitors and produced a small but significant level of protection from H2O2 toxicity in progenitors and mature oligodendrocytes. In contrast, inhibitors of both p38 and MEK reduced H2O2‐induced death most significantly in oligodendrocytes. The poly (ADP‐ribose) polymerase inhibitor, PJ34, reduced H2O2‐induced toxicity on its own but was most effective when combined with benzyloxycarbonyl‐Val‐Ala‐Asp fluoromethyl ketone or PD169316. The finding that molecular mechanisms conferring resistance to reactive oxygen species toxicity are regulated during oligodendrocyte differentiation may be of importance in designing therapies for certain neurological diseases affecting white matter.
Angiotensin II regulates tyrosine hydroxylase activity and mRNA expression in rat mediobasal hypothalamic cultures: the role of specific protein kinases
Authors: Ma Frank Y. , Grattan David R. , Bobrovskaya Larisa , Dunkley Peter R. , Bunn Stephen J.
Published: July 2004

Dopamine secreted by hypothalamic neurons is crucial in regulating prolactin secretion from the pituitary. We have examined the ability of angiotensin II (AngII) to regulate the activity of these dopaminergic neurons and thus act as a potential physiological regulator of prolactin secretion. Using a hypothalamic cell culture preparation we determined the effect of AngII on tyrosine hydroxylase activity and expression (TOH). This is important because TOH is the rate‐limiting enzyme in dopamine biosynthesis. AngII stimulated a time‐ and concentration‐dependent increase in TOH activity which was suppressed by inhibitors able to act on protein kinase A (PKA), protein kinase C (PKC) and Ca2+/calmodulin‐dependent protein kinase II (CaMPKII). An inhibitor of the mitogen‐activated protein kinase (MAPK) pathway, PD 98059, reduced basal TOH activity but the AngII response was still detectable. AngII stimulation enhanced the phosphorylation of TOH at Ser19, Ser31 and Ser40. AngII also induced a time‐dependent increase in TOH mRNA expression which was unaffected by inhibitors able to act on PKA and CaMPKII, but was abolished by inhibitors able to act on ERK and PKC. AngII responses were very much larger in cultures prepared from female when compared to male rat pups. Data from adult hypothalamic slices confirmed this sexual dimorphism and supported the role of the protein kinases noted above. Therefore AngII can regulate both the activity and expression of TOH in hypothalamic neurons employing multiple, but only partially overlapping, signaling pathways.
Interference with ubiquitination causes oxidative damage and increased protein nitration: implications for neurodegenerative diseases
Authors: Hyun Dong‐Hoon , Gray Douglas A. , Halliwell Barry , Jenner Peter
Published: July 2004

Inhibition of the proteasomal pathway for degrading abnormal proteins leads to protein aggregation, increased oxidative damage and increased protein nitration. We now show that interference with polyubiquitination has similar consequences. Expression of a dominant‐negative mutant form of ubiquitin (K48R) in NT‐2 and SK‐N‐MC cells caused decreased cell growth rates and increased oxidative damage (protein carbonyls and lipid peroxidation), nitric oxide production and elevated protein nitration. It also rendered cells highly sensitive to 4‐hydroxy‐2,3‐trans‐nonenal, a neurotoxic end‐product of lipid peroxidation, hydrogen peroxide and deprivation of growth factors. Overexpression of wild‐type ubiquitin did not produce these effects. Our data show that interference with the ubiquitin‐proteasome pathway at a different point and by a different mechanism can produce many of the common features of human neurodegenerative diseases, such as increased lipid peroxidation, protein oxidation and protein nitration. We suggest that defects in this pathway at multiple points could produce the common features of neurodegenerative diseases, and that more such defects remain to be discovered.
A novel peptide modulates α7 nicotinic receptor responses: implications for a possible trophic‐toxic mechanism within the brain
Authors: Greenfield Susan A. , Day Toni , Mann Edward O. , Bermudez Isabel
Published: July 2004

The α7 nicotinic acetylcholine receptor (nAChR) plays a key role in neural development and neurodegeneration. Here, we identify a novel, modulatory receptor ligand, a 14‐amino acid peptide (AEFHRWSSYMVHWK) derived from the C‐terminus of acetylcholinesterase (AChE). In three different in vitro preparations, this ‘AChE‐peptide’ is bioactive in a ligand‐specific and concentration‐dependent manner. First, it modulates acutely the effect of acetylcholine (ACh) on Xenopus oocytes transfected with human α7, but not α4/β2, nAChR. The action persists when intracellular calcium is chelated with BAPTA or when calcium is substituted with barium ions. This observation suggests that intracellular Ca2+ signals do not mediate the interaction between the peptide and nAChR, but rather that the interaction is direct: however, the intervention of other mediators cannot be excluded. Secondly, in recordings from the CA1 region in guinea‐pig hippocampal slices, AChE‐peptide modulates synaptic plasticity in a α‐bungarotoxin (α‐BgTx)‐sensitive manner. Thirdly, in organotypic cultures of rat hippocampus, long‐term exposure to peptide attenuates neurite outgrowth: this chronic, functional effect is selectively blocked by the α7 nAChR antagonists, α‐BgTx and methyllycaconitine, but not by the α4/β2‐preferring blocker dihydro‐β‐ethroidine. A scrambled peptide variant, and the analogous peptide from butyrylcholinesterase, are ineffective in all three paradigms. The consequences of this novel modulation of the α7 nAChR may be activation of a trophic‐toxic axis, of relevance to neurodegeneration.
Protein kinase C regulates the activity and stability of serotonin N‐acetyltransferase
Authors: Choi Bo‐Hwa , Chae Hee‐Don , Park Tae‐Ju , Oh Jisun , Lim Jinkyu , Kang Shin‐Sung , Ha Hyunjung , Kim Kyong‐Tai
Published: July 2004

Effects of protein kinase C on protein stability and activity of rat AANAT were investigated in vitro and in vivo. When COS‐7 cells transfected with AANAT cDNA were treated with phorbol 12‐myristate 13‐acetate (PMA), both the activity and protein level of AANAT were increased. These effects of PMA were blocked by GF109203X, a specific inhibitor of PKC. Moreover, PMA increased the phosphorylation of AANAT and induced the formation of AANAT/14‐3‐3ζ complex. PMA did not affect the basal level of cAMP and did not involve the potentiation of the cAMP production by forskolin, indicating that PKC‐dependent activation of adenylyl cyclase was excluded in transfected COS‐7 cells. To identify which amino acids were phosphorylated by PKC, several conserved Thr and Ser residues in AANAT were targeted for site‐directed mutagenesis. Mutations of Thr29 and Ser203 prevented the increase of enzymatic activity and protein level mediated by PMA. To explore the nature of AANAT phosphorylation, purified rat AANAT was subjected to in vitro PKC kinase assay. PKC directly phosphorylated the rat recombinant AANAT. The phosphopeptides identified by mass spectrometric analysis, and western blotting indicated that Thr29 was one of target sites for PKC. To confirm the effects of the physiological activation of PKC, rat pineal glands were treated with α1‐adrenergic specific agonist phenylephrine. Phenylephrine caused the phosphorylation of endogenous AANAT whereas GF109203X or prazosin, an α1‐adrenergic‐specific antagonist, markedly inhibited it. These results suggest that AANAT was phosphorylated at Thr29 by PKC activation through the α1‐adrenergic receptor in rat pineal glands, and that its phosphorylation might contribute to the stability and the activity of AANAT.
Synaptic scaffolding molecule interacts with Axin
Authors: Hirabayashi Susumu , Nishimura Wataru , Iida Junko , Kansaku Ai , Kishida Shosei , Kikuchi Akira , Tanaka Noriaki , Hata Yutaka
Published: July 2004

Synaptic scaffolding molecule (S‐SCAM) is a synaptic protein that consists of PDZ domains, a guanylate kinase domain, and WW domains. It interacts with N‐methyl‐d‐aspartate receptor subunits, neuroligin, and β‐catenin. Here, we identified Axin as a novel binding partner of S‐SCAM. Axin was co‐immunoprecipitated with S‐SCAM from rat brain, detected in the post‐synaptic density fraction in rat brain subcellular fractionation, and partially co‐localized with S‐SCAM in neurons. The guanylate kinase domain of S‐SCAM directly bound to the GSK3β‐binding region of Axin. S‐SCAM formed a complex with β‐catenin and Axin, but competed with GSK3β for Axin‐binding. Thereby, S‐SCAM inhibited the Axin‐mediated phosphorylation of β‐catenin by GSK3β.
Molecular characterization of Dα6 and Dα7 nicotinic acetylcholine receptor subunits fromDrosophila: formation of a high‐affinity α‐bungarotoxin binding site revealed by expression of subunit chimeras
Authors: Lansdell Stuart J. , Millar Neil S.
Published: July 2004

Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in the insect brain and are target sites for neonicotinoid insecticides. Seven nAChR subunits (four α‐type and three β‐type) have been cloned previously fromDrosophila melanogaster, the model insect system and characterized by heterologous expression. Recently, three further putative nAChR α subunits (Dα5, Dα6 and Dα7) with sequence similarity to the vertebrate α7 subunit have been identified fromDrosophilagenome sequence data but there have been no reports, as yet, of their characterization by heterologous expression. In the present study, we report the first isolation of a full‐length Dα7 cDNA and the independent molecular cloning of Dα6. Binding of nicotinic radioligands was not detected to full‐length Dα6 or Dα7 subunits when expressed alone or when or co‐expressed with other nAChR subunits inDrosophilaor mammalian cell lines, but specific cell‐surface binding of [125I]α‐bungarotoxin (Kd = 0.68 ± 0.22 nm) and [3H]methyllycaconitine (Kd = 0.27 ± 0.06 nm) was detected after expression of a subunit chimera containing the ligand‐binding domains of Dα6 fused to the C‐terminal domain of the 5‐hydroxytryptamine receptor 5HT3A. Although cell‐surface binding was not detected with a Dα7/5HT3Αchimera expressed alone, co‐expression of the two subunit chimeras resulted in significantly enhanced levels of nicotinic radioligand binding (with no change in affinity). This is the first evidence for the formation of a nAChR binding site by heterologously expressedDrosophilanAChR subunits in the absence of a co‐expressed vertebrate nAChR subunit. In addition to the formation of homomeric nAChR complexes, evidence has been obtained from both radioligand binding and co‐immunoprecipitation studies for the co‐assembly of Dα6 and Dα7 into heteromeric cell surface complexes.
Nitrosylation precedes caspase‐3 activation and translocation of apoptosis‐inducing factor in neonatal rat cerebral hypoxia‐ischaemia
Authors: Zhu Changlian , Wang Xiaoyang , Qiu Lin , Peeters‐Scholte Cacha , Hagberg Henrik , Blomgren Klas
Published: July 2004

Excessive nitric oxide (NO) production after cerebral hypoxia‐ischaemia (HI) may induce cellular injury in various ways, including reaction with superoxide to form the highly reactive peroxynitrite. We characterized the spatial and temporal formation of peroxynitrite through immunohistochemical detection of nitrosylated proteins. Nitrotyrosine immunoreactivity peaked around 3 h post‐HI and was detected in areas of injury, as judged by the loss of microtubule‐associated protein‐2 (MAP‐2) staining, in neurones, glia and endothelial cells. Nitrotyrosine staining co‐localized with three other cellular markers of injury, active caspase‐3, nuclear translocation of apoptosis‐inducing factor (AIF) and an oligonucleotide hairpin probe detecting specific DNA strand breaks. The number of nitrotyrosine‐positive cells at early time points outnumbered the cells positive for the other three markers of injury, indicating that nitrosylation preceded caspase‐3 activation. Pharmacological inhibition of neuronal and inducible nitric oxide synthase (nNOS and iNOS) using 2‐iminobiotin, which has been demonstrated earlier to be neuroprotective, significantly reduced nitrotyrosine formation and caspase‐3 activation, but not nuclear translocation of AIF, in cortex and striatum of the ipsilatral hemisphere. In summary, nitrotyrosine is an early marker of cellular injury and inhibition of nNOS and iNOS is a promising strategy for neuroprotection after perinatal HI.
Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators
Authors: Berry Mark D.
Published: July 2004

The presence of the so‐called trace amines 2‐phenylethylamine, m‐tyramine, p‐tyramine, m‐octopamine, p‐octopamine and tryptamine in the mammalian central nervous system has been known for several decades. Despite much initial interest, these amines have largely been thought of as little more than metabolic by‐products. The recent description of a family of mammalian trace amine receptors has, however, seen a resurgence of interest in the physiological role of this class of compounds. Although the trace amines are well documented to cause amphetamine‐like effects, such responses only occur at concentrations multiple orders of magnitude above normal physiological levels. As such, it seems unlikely that these responses reflect the true physiological role of the trace amines. In this article previous studies showing responses to physiologically relevant concentrations of trace amines are reviewed, along with those showing a reciprocal relationship between trace amine levels and fluctuations in basal monoaminergic tone. On the basis of these studies it is hypothesized that the trace amines function as endogenous neuromodulators of classical monoamine neurotransmitters. These effects are seen as an altered neuronal sensitivity to monoamine neurotransmitters, with no change in neuronal excitability in the absence of neurotransmitter.
Maternally‐inherited Leigh syndrome‐related mutations bolster mitochondrial‐mediated apoptosis
Authors: Carrozzo Rosalba , Rizza Teresa , Stringaro Annarita , Pierini Roberta , Mormone Elisabetta , Santorelli Filippo M. , Malorni Walter , Matarrese Paola
Published: July 2004

The key role of mitochondria in the apoptotic process is well understood, but not many data are available regarding the specific role of mitochondrial DNA mutations in determining cell fate. We investigated whether two mitochondrial DNA mutations (L217R and L156R) associated with maternally‐inherited Leigh syndrome may play a specific role in triggering the apoptotic cascade. Considering that different nuclear genetic factors may influence the expression of mtDNA mutations, we used a 143BTK– osteosarcoma cell line deprived from its own mtDNA in order to insert mutated mtDNAs. Analysis of mitochondrial features in these cybrids indicated that both mitochondrial DNA mutations produced evidence of biochemical, functional and ultrastructural modifications of mitochondria, and that these modifications were associated with an increased apoptotic proneness. Cybrids were highly susceptible to two different apoptotic stimuli, tumour necrosis factor‐α and Staurosporin. The mechanism involved was the mitochondrial ‘intrinsic’ pathway, i.e. the caspase 9‐driven cascade. More importantly, our results also indicated that the polarization state of the mitochondrial membrane, i.e. a constitutive hyperpolarization detected in cybrid clones, played a specific role. Interestingly, the different effects of the two mutations in terms of susceptibility to apoptosis probably reflect the deeper bioenergetic defect associated with the L217R mutation. This work provides the first evidence that hyperpolarization of mitochondria may be a ‘risk factor’ for cells with a deep ATPase dysfunction, such as cells from patients with maternally‐inherited Leigh syndrome.
Geochemistry and microbiology of an impounded subterranean acidic water body at Mynydd Parys, Anglesey, Wales
Authors: COUPLAND KRIS , JOHNSON D. BARRIE
Published: July 2004

Acidic, metal‐rich water that had accumulated within two abandoned, adjacent copper mines in north Wales was removed to prevent its possible catastrophic release. About 274 000 m3 of acidic (pH ∼2.4) mine water was pumped out of the mines over a 14‐week period. Concentrations of dissolved species (iron, sulfate, aluminium, copper, manganese and zinc) increased as water at lower depths within the mines was accessed. The discharged water flowed through a small wetland area, reaching the sea about 3 km north of the mine site. Analysis of the water at three sampling stations revealed that there was very little removal of aluminium and most of the heavy metals present except (ferrous) iron, which was partially removed as a result of oxidation and hydrolysis of the resulting ferric iron. The dominant bacterium in the subterranean mine water, which was essentially devoid of oxygen, was the iron‐ and sulfur‐oxidizer Acidithiobacillus ferrooxidans. The microbial populations in the pumped mine water were monitored using combined cultivation‐dependent (isolation on solid media) and cultivation‐independent (terminal restriction fragment length polymorphism and clone library) techniques. Other bacteria detected in the mine water included other iron‐oxidizers (Leptospirillum spp., ‘Ferrimicrobium acidiphilum’ and Gallionella‐like organisms) and heterotrophic acidophiles (Acidiphilium, Acidisphaera and Acidobacterium). Archaeal clones were also detected; most of these were related to methanogens. Owing to the absence of an effective remediation strategy, an estimated 7.5 tonnes of copper, 3.1 tonnes of manganese, 14.8 tonnes of zinc and 15.3 tonnes of aluminium was discharged into the Irish Sea as a consequence of the dewatering of the mines.
Right ventricular long‐axis function in relation to left ventricular systolic function
Authors: Emilsson Kent
Published: July 2004

A decrease in left ventricular (LV) systolic function is accompanied by a decrease in maximal relaxation velocity in LV long‐axis direction, but is it also accompanied by a decrease in right ventricular (RV) long‐axis function? To study this 35 consecutive patients were examined by echocardiography. Ejection fraction (LVEF) and mitral annulus motion (MAM) were used as indices of LV systolic function and tricuspid annulus motion (TAM), that is the systolic shortening in RV long‐axis direction, was used as an index of RV systolic long‐axis function. In the same way the maximal relaxation velocity in LV long‐axis direction, that is the maximal diastolic velocity of MAM (MDV MAM), has been suggested as an index of LV diastolic function the maximal diastolic velocity of TAM (MDV TAM) can be supposed to be an index of RV diastolic function measuring the maximal relaxation velocity in the RV long‐axis direction. A significant positive correlation was found between MDV TAM and MAM (r = 0·64, P<0001) and LVEF (r = 0·54, P = 0·001) and between TAM and the two studied indices of LV systolic function, with the highest correlation to MAM (r = 0·68, P<0·001) and the lowest to LVEF (r = 0·57, P<0·001). Thus, a decrease in LV systolic function is accompanied by a decrease in both systolic and diastolic RV long‐axis function, findings that probably are due to the close anatomical connection between the ventricles and to changes that occur in afterload of the RV secondary to LV systolic dysfunction.
Acute effects of nifedipine administration in pulmonary haemodynamics and oxygen delivery during exercise in patients with chronic obstructive pulmonary disease: implication of the angiotensin‐converting enzyme gene polymorphisms
Authors: Kanazawa Hiroshi , Tateishi Yoshitaka , Yoshikawa Junichi
Published: July 2004

The angiotensin‐converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance in tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). This study was designed to examine the acute effects of nifedipine administration in pulmonary haemodynamics and oxygen delivery during exercise in COPD patients with II, ID, and DD genotypes. Thirty‐three COPD patients (II = 12, ID = 11, DD = 10) with placebo or nifedipine (10 mg) underwent right heart catheterization with exercise, and systemic and pulmonary haemodynamic variables were examined. At rest, there was no significant difference in either mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) or oxygen delivery (DO2) among the three groups. However, the magnitude of mPAP or PVR after exercise was the DD > ID > II genotype. In contrast, the magnitude of DO2 after exercise was the II > ID > DD genotype. We also found that nifedipine administration significantly decreased mPAP after exercise in all the three groups. However, we found no significant difference in PVR or DO2 between placebo and nifedipine administration in all the three groups. Thus, a single administration of nifedipine may not have the clinical efficacy for the treatment of pulmonary hypertension and impaired oxygen delivery during exercise in COPD patients with different ACE gene polymorphisms.
Intermittent venous compression, and the duration of hyperaemia in the common femoral artery
Authors: Morris Rhys J. , Woodcock John P.
Published: July 2004

External compression of limbs to below‐diastolic pressure (venous compression) has been shown to produce a short‐lived hyperaemia in supply arteries. Intermittent pneumatic compression is currently under investigation therefore as a treatment for peripheral arterial disease. The optimal timing of the compression will depend on the duration of hyperaemia produced by a particular duration of compression, and the purpose of this work was to test that link. Nineteen healthy volunteers underwent intermittent compression of one leg with two compression cycles – one compressing for 10 s each time, the other for 1 min. Blood flow velocities in the common femoral artery was shown to increase on release of the compression by 38% (inter‐quartile range 27–56%) for the sequence with short duration compression, and by 57% (inter‐quartile range 37–87%) for the longer sequence (difference, P = 0·005, Wilcoxon). The hyperaemia duration above the baseline level was 37 s (inter‐quartile range 32–49 s) for the short sequence, and 54 s (inter‐quartile range 37–76 s) for the longer sequence (difference, P = 0·001, Wilcoxon). The magnitude of the change in the compression duration was not equalled by the difference in hyperaemia duration, suggesting that the physiological mechanism behind the hyperaemia is unlikely to be due solely to simple accumulation of metabolites, and a myogenic mechanism remains possible. Therapies for peripheral arterial disease need not employ long duration compression, as a greater percentage of time will be spent in hyperaemia with short duration intermittent compression.
C‐peptide: new findings and therapeutic implications in diabetes
Authors: Wahren John
Published: July 2004

In contrast to earlier views, new data indicate that proinsulin C‐peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C‐peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G‐protein coupled receptor. Ca2+‐ and MAP‐kinase dependent signalling pathways are activated, resulting in stimulation of Na+, K+‐ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C‐peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C‐peptide administration in streptozotocin‐diabetic animals results in normalization of diabetes‐induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C‐peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C‐peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C‐peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C‐peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C‐peptide is the ugly duckling that – nearly 40 years after its discovery – may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long‐term complications.
Psychometric properties of vision‐related quality of life questionnaires: a systematic review
Authors: De Boer Michiel R. , Moll Annette C. , De Vet Henrica C. W. , Terwee Caroline B. , Völker‐Dieben Hennie J. M. , Van Rens Ger H. M. B.
Published: July 2004

The increased attention for quality of life (QOL) as an outcome measure has led to the development of numerous questionnaires to assess this construct in the field of ophthalmology. This article presents a systematic review on QOL questionnaires for people with vision impairments. We systematically searched and selected the literature. Furthermore, a rating list with descriptive aspects (e.g. target population) and psychometric aspects (e.g. reproducibility) was developed. The 31 questionnaires that were included in the review were rated on the basis of criteria stated in this rating list. The questionnaires were mostly targeted at cataract patients or visually impaired persons in general. Only a few of the questionnaires demonstrated sufficient psychometric quality. A recent development is the (re‐)evaluation of questionnaires with Rasch analysis. This is one of the most important issues to which future research in this field should be directed.
Quality of light and quality of life – the effect of lighting adaptation among people with low vision
Authors: Brunnström Gunilla , Sörensen Stefan , Alsterstad Karin , Sjöstrand Johan
Published: July 2004

Purpose:  The study has investigated the effect of lighting on the daily activities (ADL) of the visually impaired in their homes by comparison before and after light adjustments were made in the kitchen, hall and bathroom. It has also investigated the additional effects on the quality of life after providing task lighting in the living room.

Method:  A total of 56 people were consecutively recruited from those receiving lighting adaptation help by the Low Vision Clinic in Göteborg. Ten persons did not complete the study. After medical examinations, lighting standards and psychosocial factors were charted. After lighting improvements were carried out in the kitchen, hall and bathroom, the subjects were randomly divided into two groups, an intervention and a comparison group. The task lighting in the living room was also improved for those included in the intervention group. Follow‐up interviews to determine ADL and quality of life were performed 6 months after lighting adaptation.

Results:  A marked effect on quality of life of the lighting in the living room was found for the intervention group. The effect on ADL of the basic lighting adaptation in kitchen, hall and bathroom for both groups was significant for tasks carried out on the working surface in the kitchen. Other activities in the kitchen and in the bathroom tended to improve but changes were not significant.

Conclusion:  The results confirm that it is possible to increase quality of life by improving the lighting conditions.
Measurements of preferred walking speed in subjects with central and peripheral vision loss
Authors: Soong G. P. , Lovie‐Kitchin J. E. , Brown B
Published: July 2004

Background:  Previous mobility studies have used Preferred Walking Speed (PWS) in order to determine the walking efficiency in terms of the Percent Preferred Walking Speed (PPWS) of visually impaired adults. PWS has been measured in previous studies using the sighted guide (SG) and non‐sighted guide (NSG) techniques. This study compared the NSG, SG and string (ST) (subjects walked by holding on lightly to a cardboard tube attached to a piece of string) techniques of measuring PWS in visually impaired subjects.

Methods:  Forty visually impaired subjects with central and peripheral vision loss were recruited. PWS was measured using the NSG, SG and ST techniques. For each technique, PWS was determined by recording the time taken for a subject to walk an unobstructed, straight 20‐m corridor.

Results:  There were no significant differences in PWS using the SG, NSG and ST techniques.

Conclusion:  For assessing walking efficiency, either the SG, NSG or ST technique could be employed when measuring PWS in visually impaired subjects.
Ten years of glaucoma blindness in Fife 1990–99 and the implications for ophthalmology, optometry and rehabilitation services*
Authors: Sinclair A. , Hinds A. , Sanders R.
Published: July 2004

The aim of this study was to determine the characteristics of the patients in Fife who were registered as blind with a main diagnosis of glaucoma between 1990 and 1999. The case notes of 87 people were studied. The average age at registration was 78 years (S.D. = 14). By the time of first referral to hospital, more than half were already aware of visual loss. Forty‐five per cent of referrals had no optometry input. Compliance with treatment was poor in at least 26% of patients. Only 44% had glaucoma surgery. There were significant findings with regard to mental health, particularly dementia, which was eventually present in 24%. At least one‐third of patients had a hearing impairment. One‐third of those registered as blind could have been registered earlier. However, staff from the local provider of rehabilitation and social work services for the blind were shown to have provided prompt and helpful support to 95% of those registered. Consideration should be given to the way in which elderly patients with advanced glaucoma are managed, with awareness of mental health and hearing problems and emphasis on early referral to rehabilitation services.
Reading errors made by children with low vision*
Authors: Douglas Graeme , Grimley Mick , McLinden Mike , Watson Linda
Published: July 2004

Previous research has shown that, on average, children with low vision lag their sighted peers in general reading development (in terms of speed, accuracy and comprehension). This study sought to examine this apparent lag by comparing the reading profiles of 25 normally sighted readers (mean age 8 years 8 months) with 25 low vision readers. The children were tested using a reading test (the Neale Analysis of Reading Ability, NARA) and were matched on the reading accuracy score produced by the test. Therefore in terms of the reading accuracy scores (and reading ages) derived from the NARA both groups were the same. The low vision readers were on average older than the normally sighted children (mean = 10 years, 5 months). When the reading profile (i.e. accuracy, comprehension and speed) was examined in the same analysis no significant effect was revealed [d.f. = 1, 48; F = 0.05; p > 0.1], but a general lag for these children is suggested (in keeping with previous research). However, a closer analysis of the reading error profile revealed the most common reading errors made by all readers in the analysis were either mispronunciations or substitutions. The low vision readers were more prone to making substitution errors than mispronunciations and the reverse was true for normally sighted readers [d.f. = 1, 48; F = 7.1; p < 0.05]. This indicates that the reading strategies adopted by low vision readers may differ from those of normally sighted readers of the same apparent reading ability.
Predicting prescribed magnification*
Authors: Wolffsohn James S. , Eperjesi Frank
Published: July 2004

Aim:  To determine the best method of estimating the optimum magnification needed by visually impaired patients.

Methods:  The magnification of low vision aids prescribed to 187 presbyopic visually impaired patients for reading newspapers or books was compared with logMAR distance and near acuity (at 25 cm) and magnification predicted by +4 D step near additions.

Results:  Distance letter (r = 0.58) and near word visual acuity (r = 0.67) were strongly correlated to the prescribed magnification as were predictive formulae based on these measures. Prediction using the effect of proximal magnification resulted in a similar correlation (r = 0.67) and prediction was poorer in those who did not benefit from proximal magnification. The difference between prescribed and predicted magnification was found to be unrelated to the condition causing visual impairment (F = 2.57, p = 0.08), the central visual field status (F = 0.57, p = 0.57) and patient psychology (F = 0.44, p = 0.51), but was higher in those prescribed stand magnifiers than high near additions (F = 5.99, p < 0.01).

Conclusions:  The magnification necessary to perform normal visual tasks can be predicted in the majority of cases using visual acuity measures, although measuring the effect of proximal magnification demonstrates the effect of stronger glasses and identifies those in whom prescribed magnification is more difficult to predict.
An ideal ocular nutritional supplement?*
Authors: Bartlett Hannah , Eperjesi Frank
Published: July 2004

The role of nutritional supplementation in prevention of onset or progression of ocular disease is of interest to health care professionals and patients. The aim of this review is to identify those antioxidants most appropriate for inclusion in an ideal ocular nutritional supplement, suitable for those with a family history of glaucoma, cataract, or age‐related macular disease, or lifestyle factors predisposing onset of these conditions, such as smoking, poor nutritional status, or high levels of sunlight exposure. It would also be suitable for those with early stages of age‐related ocular disease. Literature searches were carried out on Web of Science and PubMed for articles relating to the use of nutrients in ocular disease. Those highlighted for possible inclusion were vitamins A, B, C and E, carotenoids beta‐carotene, lutein, and zeaxanthin, minerals selenium and zinc, and the herb, Ginkgo biloba. Conflicting evidence is presented for vitamins A and E in prevention of ocular disease; these vitamins have roles in the production of rhodopsin and prevention of lipid peroxidation respectively. B vitamins have been linked with a reduced risk of cataract and studies have provided evidence supporting a protective role of vitamin C in cataract prevention. Beta‐carotene is active in the prevention of free radical formation, but has been linked with an increased risk of lung cancer in smokers. Improvements in visual function in patients with age‐related macular disease have been noted with lutein and zeaxanthin supplementation. Selenium has been linked with a reduced risk of cataract and activates the antioxidant enzyme glutathione peroxidase, protecting cell membranes from oxidative damage while zinc, although an essential component of antioxidant enzymes, has been highlighted for risk of adverse effects. As well as reducing platelet aggregation and increasing vasodilation, Gingko biloba has been linked with improvements in pre‐existing field damage in some patients with normal tension glaucoma. We advocate that vitamins C and E, and lutein/zeaxanthin should be included in our theoretically ideal ocular nutritional supplement.
Low vision service delivery: an audit of newly developed outreach clinics in Northern Ireland*
Authors: Lindsay J. , Bickerstaff D. , McGlade A. , Toner A. , Jackson A. J.
Published: July 2004

Recent publications recommend that low vision services are multi‐professional; easily accessible; freely available to all those with visual impairment; monitored by professional and patient groups, and responsive to user feedback. These standards were applied when developing low vision outreach services in Northern Ireland in 1999/2000. Results are reported of the complete clinical audit cycle, coupled with a patient satisfaction telephone questionnaire, which was used to evaluate the service. Of the 48 patients randomly selected from the list of clinic attendees, 28 (58%) were female, 27 (56%) over 80 years of age and 38 (78%) had a primary ocular diagnosis of age related macular degeneration (AMD). Of the 46 low vision aids issued at patients’ first appointments, 30 (67%) were illuminated stand magnifiers and 29 (63%) had magnification levels of ×5 or less. A total of 46 (96%) patients reported that they had benefited from low vision services.
Quality of Care for Patients with Type 2 Diabetes Mellitus in the Netherlands and the United States: A Comparison of Two Quality Improvement Programs
Authors: Valk Gerlof D. , Renders Carry M. , Kriegsman Didi M. W. , Newton Katherine M. , Twisk Jos W. R. , van Eijk Jacques Th. M. , van der Wal Gerrit , Wagner Edward H.
Published: July 2004

Objective. To assess differences in diabetes care and patient outcomes by comparing two multifaceted quality improvement programs in two different countries, and to increase knowledge of effective elements of such programs.

Study Setting. Primary care in the ExtraMural Clinic (EMC) of the Department of General Practice of the Vrije Universiteit in Amsterdam, the Netherlands, and the Group Health Cooperative (GHC), a group‐model health maintenance organization (HMO) in western Washington State in the United States. Data were collected from 1992 to 1997.

Study Design. In this observational study two diabetes cohorts in which a quality improvement program was implemented were compared. Both programs included a medical record system, clinical practice guidelines, physician educational meetings, audit, and feedback. Only the Dutch program (EMC) included guidelines on the structure of diabetes care and a recall system. Only the GHC program included educational outreach visits, formation of multidisciplinary teams, and patient self‐management support.

Data Collection. Included were 379 EMC patients, and 2,119 GHC patients with type 2 diabetes mellitus. Main process outcomes were: annual number of diabetes visits, and number of HbA1c and blood lipid measurements. Main patient outcomes were HbA1c and blood lipid levels. Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices.

Principal Findings. In the EMC process outcomes and glycemic control improved more than at GHC, however, GHC had better baseline measures. There were no differences between programs on blood lipid control. During follow‐up, intensification of pharmacotherapy was noted at both sites. Differences noted between programs were in line with differences in diabetes guidelines.

Conclusions. Following implementation of guidelines and organizational improvement efforts, change occurred primarily in the process outcomes, rather than in the patient outcomes. Although much effort was put into improving process and patient outcomes, both complex programs still showed only moderate effects.
Patient Satisfaction, Treatment Experience, and Disability Outcomes in a Population‐Based Cohort of Injured Workers in Washington State: Implications for Quality Improvement
Authors: Wickizer Thomas M. , Franklin Gary , Fulton‐Kehoe Deborah , Turner Judith A. , Mootz Robert , Smith‐Weller Terri
Published: July 2004

Objective. To determine what aspects of patient satisfaction are most important in explaining the variance in patients' overall treatment experience and to evaluate the relationship between treatment experience and subsequent outcomes.

Data Sources and Setting. Data from a population‐based survey of 804 randomly selected injured workers in Washington State filing a workers' compensation claim between November 1999 and February 2000 were combined with insurance claims data indicating whether survey respondents were receiving disability compensation payments for being out of work at 6 or 12 months after claim filing.

Study Design. We conducted a two‐step analysis. In the first step, we tested a multiple linear regression model to assess the relationship of satisfaction measures to patients' overall treatment experience. In the second step, we used logistic regression to assess the relationship of treatment experience to subsequent outcomes.

Principal Findings. Among injured workers who had ongoing follow‐up care after their initial treatment (n=681), satisfaction with interpersonal and technical aspects of care and with care coordination was strongly and positively associated with overall treatment experience (p<0.001). As a group, the satisfaction measures explained 38 percent of the variance in treatment experience after controlling for demographics, satisfaction with medical care prior to injury, job satisfaction, type of injury, and provider type. Injured workers who reported less‐favorable treatment experience were 3.54 times as likely (95 percent confidence interval, 1.20–10.95, p=.021) to be receiving time‐loss compensation for inability to work due to injury 6 or 12 months after filing a claim, compared to patients whose treatment experience was more positive.
Trust in Insurers and Access to Physicians: Associated Enrollee Behaviors and Changes over Time
Authors: Balkrishnan Rajesh , Hall Mark A. , Blackwelder Stephen , Bradley Donald
Published: July 2004

Objective. Most studies of trust in the medical arena have focused on trust in physicians rather than trust in health insurers, and have been cross‐sectional rather than longitudinal studies. This study examined associations among trust in a managed care insurer, trust in one's primary physician, and subsequent enrollee behaviors relating to source of care. The study also documents changes in trust in the study population following the disclosure of physician incentives.

Study Setting. A medium‐sized (300,000 member) HMO, located in the southeastern United States.

Data Collection. One to two years after baseline, we randomly resurveyed a quarter (n=558) of the initial study population of a large intervention study designed to measure the impact of disclosing HMO financial incentives on patient trust. This follow‐up study was also designed to measure the effects of trust on source of care.

Analyses. Multivariate regression analyses of survey data examined associations between baseline levels of trust and subsequent enrollee behaviors such as using a non‐PCP physician without a PCP referral, as well as changes in trust since baseline.

Results. High baseline insurer trust was associated with a lower probability of a patient seeking care from a non‐PCP physician (OR=0.55, 95 percent CI: 0.33, 0.91). No long‐term effects of prior disclosure of financial incentives were observed. Overall, there was a slight increase in overall trust in the insurer (1.8 percent, p<.05) but no change in trust in one's primary physician. The increase in insurer trust was primarily restricted to 23 percent of the enrollees who had changed their PCPs following the baseline survey (6.6 percent, p<.01). In multivariate analyses, changing physicians was the most significant predictor of increased insurer trust (OR=2.17, 95 percent CI: 1.37, 3.43).

Conclusions. Trust in one's insurer seems to change over time more than trust in one's primary physician, and is predictive of enrollee behaviors such as seeking care from other physicians. The ability to change physicians seems to increase trust in the insurer.
Context or Composition: What Explains Variation in SCHIP Disenrollment?
Authors: Phillips Julie A. , Miller Jane E. , Cantor Joel C. , Gaboda Dorothy
Published: July 2004

Objective. To investigate (1) the relative contributions of family and contextual characteristics to observed variation in disenrollment rates from the State Children's Health Insurance Program (SCHIP), and (2) whether context explains observed family‐level patterns.

Data Sources. We use secondary data on 24,628 families enrolled in New Jersey's SCHIP program (NJ KidCare), and county‐level data from the Area Resource File, the Census, and the NJ FamilyCare provider roster.

Study Design. Information on family characteristics, SCHIP plan, and dates of enrollment and disenrollment are taken from NJ KidCare administrative records, which provided surveillance data from January 1998 through April 2000.

Data Collection/Analysis. We estimate a multilevel discrete‐time‐hazards model of SCHIP disenrollment.

Findings. Families enrolled in plans involving cost‐sharing, blacks, and those with only one enrolled child have higher than average rates of disenrollment. Disenrollment rates for blacks are lower in counties with a high share of black physicians. These characteristics account for part of the intercounty variation in disenrollment rates; remaining intercounty variation is largely explained by physician density or population density.

Policy Implications. It may be worthwhile to pay special attention to black families and counties with high disenrollment rates to address the reasons for their lower retention. Addressing cultural differences between physician and client and the geographic distribution of medical providers might reduce disenrollment.