bluuebunny/crossref_metadata_2025 huggingface dataset:
The reliability of a computerised crossed‐cylinder aberroscope for measuring the optical aberrations of the human eye
Authors: Cox M. J. , Merino N.
Published: March 2003

Purpose: To assess the reliability of a new computerised method of measuring the monochromatic aberrations on the human eye.

Methods: A crossed‐cylinder aberroscope which has been modified to provide semi‐automated objective measurements of the wavefront aberration of the human eye was used to collect repeated measurements in a sample of ten normal subjects. For each subject one eye was chosen and ten images of the aberrations in that eye were collected. All the images were analysed once to measure the inter‐image variability. One image from each eye was measured ten times to measure the intra‐image variability. To assess the reliability we used a one‐way analysis of variance designed to measure changes in the two‐dimensional wavefront aberration function.

Results: A significant difference existed between the wavefront aberration measured in each subject. That is, inter‐image and intra‐image errors in the repeated measurements were small enough to allow the different subjects to be discriminated from one another.

Conclusions: The reliability is satisfactory under the conditions of multiple measurements of the same eye from different images (inter‐image reliability) and multiple measurement of the same image (intra‐image reliability).
Depth perception in telestereoscopic systems
Authors: Loukiades O. , Charman W. N. , Jennings J. A. M.
Published: March 2003

Three‐dimensional displays are being increasingly used in technological and entertainment applications, including ‘virtual reality’ systems. In many such displays the imagery is such as to effectively introduce interpupillary distances (IPDs) and magnifications which differ from those applying in conventional naked‐eye viewing. Geometrical considerations predict that depth discrimination should be enhanced by increased effective IPD. Such enhancement could be useful in, for example, stereoscopic systems for remote handling applications. Experiments are described in which both depth discrimination at threshold and suprathreshold judgements of relative depth were explored as a function of effective IPD and magnification. Enhanced IPD gave real benefits in threshold judgements but magnification was less useful, possibly because of limitations in the optical quality of the devices used. The relevance of these results to present and future stereoscopic display systems is discussed.
The effects of viewing modality and positioning of a car head‐up display (HUD) on response times
Authors: Wolffsohn James S. , Edgar Graham K. , McBrien Neville A.
Published: March 2003

Purpose: Car HUDs which, unlike those in aircraft, do not usually overlay the outside world, have been positioned in a variety of locations. With the likely increase of HUDs in cars, it is important to establish the optimum location to place the virtual HUD image. The effects of presenting the virtual HUD image to just one eye, or both eyes, while the outside world (traffic lights) is viewed binocularly, were also assessed.

Methods: Six subjects responded to changes in simulated traffic lights and a HUD image. Response times and the number of occasions a change was missed were recorded. The HUD was presented at a range of eccentricities of up to 10° horizontally and vertically, relative to the traffic lights. The outside world was always seen in both eyes, with the HUD image being viewed monocularly and binocularly for each of the eccentricities tested.

Results: Response times to changes in the outside world view (traffic lights) are significantly faster (P < 0.01) than to changes in the HUD image. Response times to changes in the HUD virtual image and the amount of information missed increased with increasing eccentricity. More information was missed and response times were slower with a monocular HUD than a binocular HUD.

Conclusion: The optimum location based on response times and information gathering was found to be approximately 5° diagonally down from the driver's line of sight. A virtual HUD image seen in both eyes is preferable. It is of concern that gross outside world changes are missed when drivers attend to the virtual HUD image and the outside world.
Bias and precision of letter chart threshold estimates: a simulation study
Authors: Gilchrist Jim
Published: March 2003

Purpose: An ideal letter chart should give accurate (precise and unbiased) estimates of true threshold over the whole range of the chart. Precision and bias may be affected by chart design, scoring procedure and patient response characteristics.

Methods: Accuracy of acuity estimates on Bailey‐Lovie (BL) and Snellen (SN) charts were evaluated by computer simulation. Subjects' psychometric acuity functions were modelled using a Weibull function with constant slope and variable threshold level. The model subject gave 500 simulated ‘readings’ of each chart with true thresholds covering the full range of each chart. For each reading a number of scoring procedures were employed based on combinations of: (a) stopping criterion; and (b) estimation rule.

Results: Results show that: (1) the BL chart is not necessarily more accurate than SN, but its precision and bias are much more consistent across the threshold range. (2) Accuracy of both charts depends critically on scoring procedure and is affected more by choice of stopping criterion than by choice of estimation rule.

Conclusion: A recommended scoring procedure for the Bailey‐Lovie chart based on simulations is: stop reading when 3 errors occur in one line, and estimate threshold as the last letter read correctly.
The influence of hyperglycaemia upon the colour vision of patients with diabetes mellitus
Authors: North R. V. , Cooney O. , Chambers D. , Dolben J. , Owens D. R.
Published: March 2003

Purpose: To investigate whether an increase in plasma glucose level had an influence upon the colour vision of patients with non‐insulin dependent diabetes mellitus (NIDDM).

Methods: A total of 16 patients with NIDDM were investigated, mean age and duration of NIDDM 59.8 and 4.7 years, respectively. The colour vision was assessed every 30 minutes for 4 hours using a Desaturated D15 under three conditions: (1) meal tolerance test (n = 8); (2) stable plasma glucose conditions, i.e. fasting (n = 8); and (3) intravenous glucose tolerance test (n = 8).

Results: The total error score does not vary significantly under the three test conditions. The influence of the plasma glucose upon the TES is not significant, even though levels of up to 22.7 mmol/l were recorded.

Conclusion: Colour vision does not appear to be influenced by acute increases in plasma glucose concentrations, unlike the deterioration of colour vision found during hypoglycaemia.
Differential effects of luminance and contrast on acuity thresholds across the visual field
Authors: de Lizarduy Jorge Martinez , Whitaker David
Published: March 2003

Purpose: To investigate the effects of contrast and luminance on acuity thresholds across the visual field. This may shed some light on the important question of why some visual thresholds change only slowly as a function of eccentricity, whereas others fall off extremely quickly.

Methods: Resolution thresholds for Gabor patches were measured in the nasal visual field using a modified yes/no staircase procedure. The effect of contrast was examined by changing the physical contrast of the Gabor stimuli between the values of 3.125 and 100%. The effect of luminance was investigated using high contrast Gabor stimuli but varying luminance over 2.7 log units with the use of neutral density filters. Natural pupils were used throughout.

Results: The variation in resolution thresholds as a function of eccentricity was well described by the equation T = T0/[+(E/E2)], where T represents threshold, T0 threshold at the fovea, E is eccentricity and E2 is a parameter which describes the rate of decline in performance, representing the eccentricity at which the foveal resolution threshold halves. Changes in contrast resulted in the same logarithmic change in resolution threshold at all eccentricities, leaving the E2 value unchanged. Thresholds were proportional to the logarithm of contrast, and transforming the data in this way accounted for 98% of the variance in the eccentricity and contrast dependent data. Variations in luminance produced quite different effects, with E2 becoming significantly greater as luminance was reduced. At all eccentricities, resolution thresholds were proportional to the logarithm of retinal illuminance, but the gradient of this relationship changed markedly as a function of eccentricity, becoming close to zero at the higher eccentricities studied.

Conclusions: The differential effects of contrast and luminance on acuity thresholds can be understood in terms of a pyramidal model of early vision in which reductions in suprathreshold contrast affect the signal by the same amount in all early visual filters, whereas reductions in luminance have a selective effect on smaller visual filters which are more susceptible to quantal noise.
Movement hyperacuity deficit in childhood amblyopia
Authors: Kelly Susanne , Buckingham Terry
Published: March 2003

Besides a loss in resolution acuity, amblyopia results in deficits in a number of visual functions in the amblyopic eye. We describe impairment in oscillatory movement displacement thresholds (OMDT) in childhood amblyopia. 50 subjects (aged 74 ± 16 months) with strabismic, anisometropic or mixed aetiology amblyopia were compared to a group of 24 age‐matched controls. Thresholds were demonstrated to be in the hyperacuity range and were not related to the visual acuity. OMDT was significantly reduced in the amblyopic eye compared to the dominant and control eyes (P < 0.05) only when no stereoscopic responses were demonstrated. When gross stereopsis was present, thresholds for the amblyopic eyes were comparable with both the dominant and control eyes. The results are discussed in terms of binocular competition and developmental anomaly.
The effect of glare upon visual performance in keratoconus
Authors: Barrett Brendan T. , Gray Lyle S.
Published: March 2003

Purpose: The irregular optics of keratoconus produce visual deficits not revealed by standard visual acuity measurements. Non‐standard tests, such as low contrast visual acuity, contrast sensitivity measurement and glare sensitivity may provide a fuller description of the visual deficit in keratoconus. The present study investigates the effect of glare upon visual performance in keratoconus using a variety of clinical tests.

Methods: One keratoconic subject (aged 28 years), and one visually normal subject (aged 27 years) participated in the study. Monocular log MAR acuities (high and low contrast) and contrast sensitivities (Pelli‐Robson) were measured in the presence and absence of a glare source (Mentor BAT).

Results: (1) High contrast acuity was unaffected by glare in the normal subject, but was reduced by 0.20 log units in the keratoconic subject. (2) Glare reduced low contrast acuity by 0.15 log units in the normal subject, and by 0.70 log units in the keratoconic subject. (3) Contrast sensitivity was reduced by 0.30 log units due to glare in the normal subject, and by 0.50 log units in the keratoconic subject.

Conclusions: Glare is a significant factor in reducing visual performance in keratoconus. The effects of glare are most pronounced for low contrast visual acuity.
Investigation of retinitis pigmentosa using the multifocal electroretinogram
Authors: Chan H. L. , Brown B.
Published: March 2003

Retinitis pigmentosa (RP) patients have pathological changes in both the macula and the periphery, and are known to have abnormal electroretinograms (ERGs). The response densities measured by the multifocal electroretinogram (MERG) in the macula and pericentral retina were greatly reduced in RP. In photopic conditions, some patients had relatively better ERG responses in the macula than in the pericentral retina, and this agreed with the finding that there is usually relatively well‐preserved macular function in RP. In scotopic conditions, both macula and pericentral retina gave poor responses. There was very little increase in response as stimulus luminance increased in RP. The topographical mapping of the MERG results can provide objective, localized assessment of retinal function.
The value of a phenol red impregnated thread for differentiating between the aqueous and non‐aqueous deficient dry eye
Authors: Patel S. , Farrell J. , Blades K. J. , Grierson D. J.
Published: March 2003

To determine the clinical viability of a phenol red impregnated cotton thread in differentiating between normal, aqueous deficient and non‐aqueous deficient dry eyes.

Subjects were recruited on the basis of subjective symptoms, tear stability, rose bengal staining, Schirmer test, conjunctival hyperaemia, patency and number of meibomian glands, presence of mucin strands, appearance of lower tear meniscus. Based on the outcome of the tests, subjects were categorised as either aqueous deficient dry eyes, non‐aqueous dry eyes or normals. Subjects were randomised and a thread was applied by inserting into the lower fornix of the right eye and leaving the thread in place for 120 sec. All data was collected under similar ambient conditions. After gathering all the data, the codes were broken.

Mean (±S.D.) thread wetting values were, all dry eyes (n=59) 18.4 mm (5.9). Aqueous deficient dry eyes (n=35), 15.5 mm (4.6). Non‐aqueous deficient dry eyes [n=24], 22.7 mm (5.0). For the normals (n=38), 19.4 mm (5.0). Differences between (i) normals and aqueous deficient dry eyes and (ii) aqueous deficient and non‐aqueous deficient dry eyes were significant (p=0.01). Difference between all dry eyes and normals was not significant. For the aqueous deficient and non‐aqueous deficient dry eyes only, using a cut‐off value of 20 mm the calculated sensitivity and specificity values were 86% and 83% respectively.

This cotton thread test can effectively differentiate between aqueous deficient and non‐aqueous deficient dry eye.
Effect of parental myopia on the development of myopia in Hong Kong Chinese
Authors: Edwards M. H.
Published: March 2003

A representative sample of Hong Kong Chinese children was followed from 7 to 12 years of age. Refractive error was measured every year (n=123 at age 7 years andn=83 at age 12 years), the axial length of the eye was measured at age 12 years (n=81) and the refractive status of the parents was also determined. Thirty‐one percent of the parents in the sample were myopic and at the age of 12 years 53% of the children were myopic. There was no association between the refractive status of the parents and whether or not a child had myopia. The probability of a 12‐year‐old child with early‐onset myopia having at least one myopic parent was 0.55 and the probability of myopic parents having a myopic child was 0.6. There was no difference in the refractive error or the axial length of 12‐year‐old children according to whether neither, one or both parents were myopic. The genetic influence on myopia may be different in Caucasian and Chinese children, although it is also possible that non‐expression of the genotype in the parents may have confounded the determination of the inheritance pattern of myopia in Hong Kong Chinese children.
A study of the accuracy of corneal reflection pupillometers
Authors: Obstfeld Henri , Chou B. Ralph
Published: March 2003

We studied the accuracy of nine corneal reflection pupillometers made by three manufacturers, because, at the time of investigation, we could not find any information about their accuracy. For this purpose two steel balls separated by spacer bars, were positioned to simulate nominal inter‐pupillary distance (PD) measurements of 55, 60, 65 and 70 mm. Ten measurements of each ‘PD’ for distance vision, were made by two experienced observers, with each instrument. We found that interobserver differences in measurement were clinically insignificant most of the time, although some data sets were significantly different statistically. The most consistent and accurate measurements of PD were achieved with PD 65 mm. The average error in mean value of the measurements for all PD’s, was 2.3 mm, and the average of the standard deviation in our measurements, was 0.26 mm. Significant sources of error were poor eye relief in all instruments evaluated, as well as friction in the scale adjustment mechanism in some instruments. Our findings show that while a given pupillometer may be relied upon to give consistent readings (within the limits of clinically acceptable error), its accuracy should be checked periodically, especially for very small and very large PD measurements.
The influence of contour line size and location on the reproducibility of topographic measurement with the Heidelberg Retina Tomograph
Authors: Roff Emma J. , Hosking Sarah L. , Barnes Derek A.
Published: March 2003

Background: the recommended contour line (CL) location with the Heidelberg Retina Tomograph (HRT) is on the inner edge of Elschnig's scleral ring. This study investigated HRT parameter reproducibility when: (i) the CL size is altered relative to Elschnig's ring; (ii) the CL is either redrawn or imported between images.

Methods: using the HRT, seven 10° images were acquired for 10 normal volunteers and 10 primary open angle glaucoma (POAG) subjects. A CL was drawn on one image for each subject using Elschnig's scleral ring for reference and imported into subsequent images. The CL diameter was then (a) increased by 50 μm; (b) increased by 100 μm; and (c) decreased by 50 μm. To investigate the effect of the method of contour line transfer between images a CL was: (1) defined for one image and imported to 6 subsequent images; (2) drawn separately for each image.

Results: parameter variability improved as the size of the CL increased for the normal group relative to Elschnig's ring but was unchanged in the POAG group. The export/import function (method 1) resulted in better parameter reproducibility than the redrawing method for both groups.

Conclusions: the exporting and importing function resulted in better parameter variability for both subject groups and should be used for transferring CLs across images for the same subject. Increasing the overall CL size relative to Elschnig's scleral ring improved the reproducibility of the measured parameters in the normal group. No significant difference in parameter variability was observed for the POAG group. This suggests that the reproducibility of HRT images are affected more by the variation in topography between images than change in CL definition.
The effect of conventional CR39 and Fresnel prisms on high and low contrast acuity
Authors: Cheng Desmond , Woo George C.
Published: March 2003

The effect of conventional CR39 and Fresnel prisms on high and low contrast letter acuity was studied. Visual acuity of the fully corrected better eyes of 15 subjects was measured with the high (90%) and low (10%) contrast logMAR letter charts, while they wore prisms of varying power. The results showed that when the power of the conventional CR39 prism and the Fresnel prism reached 10 prism dioptres and 5 prism dioptres, respectively, significant reduction (1 tail t‐test, p<0.05) of the high and low contrast acuity occurred. The Fresnel prism caused a significantly greater acuity reduction than the conventional CR39 prism for powers ranging from 5 to 30 prism dioptres for both contrasts. The rate of acuity reduction with increasing prism power was greater with the low contrast targets than with the high contrast targets for both prisms. In addition, the rate of acuity reduction with increasing prism power was greater with the Fresnel prism than with the conventional CR39 prism for both contrasts. The conventional CR39 prism reduced acuity by a ratio of about 0.8–0.9 of that of the Fresnel prism for powers ranging from 5 to 20 prism dioptres and by about 0.7 for 30 prism dioptres. These ratios applied for both high and low contrast acuity, and therefore were independent of the level of contrast used.
Residual visual functions of guide dog owners in the UK
Authors: Refson K. , Jackson A. J. , Dusoir A. E. , Archer D. B.
Published: March 2003

Numbers of guide dog owners (GDOs) in the United Kingdom reached 4700 by the end of 1998. Despite this growing trend, little is known about the nature of their visual loss. This paper reports the results of a national three‐centre investigation into the residual visual functions and ophthalmic conditions of guide dog owners. Random samples of GDOs (Scotland n=82, England n=77, and Northern Ireland n=87) underwent a detailed visual analysis and interview. GDOs had an overall median age of 53 years. Nationally, they make up just 2.4% of the registered blind population. All GDOs were found to have profound loss of visual acuity, contrast sensitivity or visual fields, but only 43% were totally blind. GDOs in Scotland retained higher levels of residual visual function than those in the other two regions. The main causes of visual loss were congenital and early onset degenerative eye disease (retinitis pigmentosa 18%, optic atrophy 10%). Results taken in conjunction with epidemiological registration trends suggest that the past growth in numbers of GDOs is unlikely to be sustainable. Implications for mobility service providers are discussed. It is suggested that increased optometric input and a multidisciplinary approach could assist present and potential guide dog owners.
Corneal surface area: an index of anterior segment growth
Authors: Stone Richard A. , Lin Ton , Sugimoto Reiko , Capehart Cheryl , Maguire Maureen G. , Schmid Gregor F.
Published: March 2003

Corneal surface area and perimeter were assessed as novel indices to monitor anterior segment growth, using chicks reared under different photoperiods. We obtained central and mid‐peripheral corneal curvatures using photokeratometry. Anatomical tracings of the anterior corneal surface also were made from freeze‐dried non‐fixed preparations of the anterior segments of the same eyes. Using either photokeratometry or anatomical data, the profile of the anterior corneal surface was fit to a general equation for conical sections; corneal surface area was estimated from surfaces of revolution. Optical techniques modeled the chick cornea as a circle or as an ellipse closely resembling a circle. The anatomical technique, in contrast, modeled the chick corneal profile as a hyperbola. Potential explanations of this discrepancy are discussed. Regardless of which model is evaluated, the corneal surface area and perimeter of two‐week‐old chicks are affected by the photoperiod of rearing. Corneal surface area in particular proved more sensitive than conventional measurements in identifying anterior segment effects of rearing under different photoperiods. Analysis of corneal area may prove useful in evaluating the mechanisms governing anterior segment growth.
Intraocular lens calculation for cataract after previous radial keratotomy
Authors: Stakheev Anton A.
Published: March 2003

Purpose: The purpose of this study is to discuss the major reasons for the hyperopic shift after cataract surgery following radial keratotomy (RK) and to find potential methods to improve the prediction of intraocular lens power (IOLP).

Methods: The results for 18 cataract surgery eyes that had undergone RK were analysed retrospectively. The IOLP was calculated using Haigis, Hoffer Q, and SRK/II formulae with different keratometric measurements. Theoretical IOLP miscalculation (ΔIOLPK) was assessed in order to define the optimal combination of different keratometric parameters and intraocular lens prediction formula.

Results: The research revealed a significant temporary hyperopic shift after cataract surgery, the maximum value of which was noted in the first week post‐operatively. Standard keratometers and placido‐topography systems overestimate corneal power after RK. Corneal power overestimation correlates significantly with the spherical equivalent change after RK. Theoretical formulae (Haigis, Hoffer Q) produced the lowest ΔIOLPK using calculated corneal powers derived from spherical equivalent change.

Conclusions: Standard autokeratometry significantly overestimates corneal power after RK performed for moderate and high myopia. The use of calculated corneal power and third‐generation theoretical formulae seems to be the most appropriate for IOLP prediction.
HIV‐Associated Disorders in Fat Distribution and Lipid Metabolism
Authors: Abourjaily Paul , Small Franklin
Published: March 2003

HIV‐associated lipodystrophy is most commonly characterized by fat redistribution and/or metabolic changes, such as reduced lipid metabolism or impaired glucose tolerance. Despite the growing recognition of this disorder, its causes, characteristics, consequences, and optimal treatment are not fully understood. This review examines the current understanding of the etiology of this syndrome, its acute and long‐term implications for affected HIV‐infected patients, and treatment strategies currently under investigation, including changes in antiretroviral regimens, and the use of insulin‐sensitizing agents, growth hormones, and exercise regimens.
Flavonoids: Diet and Health Relationships
Authors: Prior Ronald L. , Cao Guohua
Published: March 2003

Flavonoids and/or phenolic acids are the major components responsible for antioxidant capacity in fruits and vegetables. Recent research has shown that flavonoids are absorbed in humans, although the bioavailablity of these dietary components is not completely clear. Some epidemiological evidence demonstrates a reduced risk of cardio‐ and cerebrovascular diseases in subjects with a high fruit and vegetable (flavonoid) intake. Investigations performed in vitro or in vivo in experimental animals suggest that some of the flavonoids have chemopreventive effects against certain forms of cancers. Flavonoids are potentially beneficial to cardio‐ and cerebrovascular systems due to their antioxidant activity against low density lipoprotein (LDL) oxidation, inhibition of platelet aggregation, and protection against capillary fragility. Flavonoids showed anti‐inflammatory, antiarthritic, and antiallergic activities in vitro, and, thus, may have potential applications in preventing and treating other diseases.
Clinical Implications of Household Food Security: Definitions, Monitoring, and Policy
Authors: Cook John T.
Published: March 2003

Poverty‐related food insecurity is a reality that many clinicians in nutrition and health care encounter either directly or indirectly. It is associated with both overnutrition and undernutrition, but it is not congruent with malnutrition. Food insecurity affects human development and health throughout the lifecycle, but can be particularly harmful during critical or vulnerable stages early and late in life. Understanding the causes and consequences of food insecurity and knowing how to identify them can improve the quality and effectiveness of clinical care, and facilitate prevention and treatment of many kinds of health problems. Numerous public policies and programs exist to ameliorate and prevent poverty‐related food insecurity. However, the resources to support them ebb and flow with the politics of annual state and federal budgetary cycles. Support and need for these social‐safety‐net programs also vary with business cycles. Unfortunately, need often expands as support shrinks along with employment and government revenues during recessions, and shrinks as support expands along with employment and government revenues during expansions.
Pharmacologic B‐Vitamin Therapy for Hyperhomocysteinemia in Dialysis Patients: Has the Time Come?
Authors: Friedman Allon N.
Published: March 2003

Hyperhomocysteinemia, the state of elevated plasma homocysteine levels, is an independent risk factor for atherothrombosis and arteriosclerosis. For incompletely understood reasons, renal disease appears to predispose to hyperhomocysteinemia. In fact, as renal function declines, plasma homocysteine levels rise. Mild to moderate hyperhomocysteinemia is almost universal among end‐stage renal disease (ESRD) patients, who have negligible functioning renal mass. This tendency towards a hyperhomocysteinemic state may partially explain the dramatically high rate of cardiovascular morbidity and death seen in this population. Hyperhomocysteinemic subjects with normal kidney function can usually reduce or normalize homocysteine levels with modest B‐vitamin (folic acid, vitamin B6, vitamin B12) supplementation. However, subjects with reduced renal function require much higher (“pharmacologic”) B‐vitamin doses to achieve equivalent reductions, while ESRD subjects are resistant to even massive doses. Study design flaws and the inclusion of potentially B‐vitamin‐deficient subjects in homocysteine‐lowering trials has made interpretation of this literature difficult. Nonetheless, it appears that the modest standard daily dialysis vitamin supplements are equivalent to pharmacologic B‐vitamin therapy in lowering homocysteine levels in ESRD patients and should be the recommended method of treatment in this population at the present time.
Leukocyte proteinases in wound healing: roles in physiologic and pathologic processes
Authors: Barrick Brooke , Campbell Edward J. , Owen Caroline A.
Published: March 2003

Leukocytes express a number of proteinases which play critical roles in physiologic processes during wound healing. However, if the activity of these proteinases is uncontrolled, they can contribute to devastating tissue injury that can affect most organ systems. Until recently, little was known about the mechanisms by which leukocytes retain the activity of their proteinases within the extracellular space which contains highly effective proteinase inhibitors. Studies of the cell biology of leukocyte proteinases have begun to identify the mechanisms by which proteinases can circumvent the effects of physiologic proteinase inhibitors. Herein, we will review the cell biology of leukocyte proteinases, and we will discuss the mechanisms by which leukocyte proteinases can contribute to physiologic processes occurring during wound healing, as well as their roles in pathologic processes.
Mitogenic activity and cytokine levels in non‐healing and healing chronic leg ulcers
Authors: Trengove Naomi J , Bielefeldt‐Ohmann Helle , Stacey Michael C
Published: March 2003

The cause of impaired healing in chronic leg ulcers is not known. However, recent attempts to modify the healing process have focused on adding growth factors to stimulate healing and have failed to produce dramatic improvements in healing. This study used a unique model of chronic wound healing in humans to obtain wound fluid samples from chronic venous leg ulcers that had changed from a nonhealing to a healing phase. These samples were used to assess cytokine and growth factor levels, and mitogenic activity in these nonhealing and healing chronic wounds. The pro‐inflammatory cytokines interleukin‐1, interleukin‐6 and tumor necrosis factor‐αwere found to be present in significantly higher concentrations in wound fluid from nonhealing compared to healing leg ulcers. There were detectable levels but, no significant change in the levels of platelet derived growth factor, epidermal growth factor, basic fibroblast growth factor or transforming growth factor‐βas ulcers healed. Wound fluid was added to fibroblasts in vitro to assess mitogenic activity. There was a significantly greater proliferative response to healing wound fluid samples compared to nonhealing samples. These results suggest that healing may be impaired by inflammatory mediators rather than inhibited by a deficiency of growth factors in these chronic wounds.
Adenoviral‐mediated gene transfer in wound healing: acute inflammatory response in human skin in the SCID mouse model
Authors: Sylvester Karl G , Nesbit Mark , Radu Antoneta , Herlyn Meenhard , Adzick N. Scott , Crombleholme Timothy M
Published: March 2003

The use of an adenoviral vector as a means of therapeutic protein delivery for the treatment of impaired wound healing is a potentially effective application of current gene transfer techniques. This study was designed to investigate the ability of adenovirus to mediate gene transfer in healing wounds in human skin in vivo. The human skin/severe combined immunodeficient mouse chimera model was used to study both the response of human tissue to adenoviral infection and the nature of the acute inflammatory response. The effects of adenoviral infection and transgene expression on the rate and quality of human wound healing were then investigated. Cell‐ and species‐specific monoclonal antibodies were used to characterize the resident skin cell types participating in wound repair, the inflammatory response, and the proliferative potential of adenovirus‐treated compared to control skin. Our studies show that, following wounding, normal skin architecture is restored in the presence of adenoviral infection equivalent to noninfected controls. Despite an increased acute inflammatory response after adenovirus injection, no difference in the healing capabilities of wounded skin was observed, suggesting that adenovirus‐mediated gene transfer for growth factor‐mediated acceleration of wound healing may be feasible.
Models for use in wound healing research: A survey focusing on in vitro and in vivo adult soft tissue
Authors: Gottrup Finn , Ågren Magnus S , Karlsmark Tonny
Published: March 2003

Many different factors must be considered before selecting a wound healing model to use for a specific study. A wide variety of models have been developed that examine different aspects of the repair response, both in vitro and in vivo. In this review article, we focus on those systems that are most widely used for studies on adult soft tissue healing. Advantages and disadvantages of each are discussed, along with relevant background information to help guide decision‐making.
Randomized trial of topically applied repifermin (recombinant human keratinocyte growth factor‐2) to accelerate wound healing in venous ulcers
Authors: Robson Martin C , Phillips Tania J , Falanga Vincent , Odenheimer Daniel J , Parish Lawrence Charles , Jensen Jeffrey L , Steed David L
Published: March 2003

About 600,000 people in the United States are estimated to be affected by venous ulcers. The cornerstone of care of chronic venous ulcers involves the application of compression bandages. Other therapies include treatment of associated infection, treatment for edema and inflammation, and debridement when necessary. Repifermin, a recombinant human KGF‐2 (fibroblast growth factor‐10), exerts a proliferative effect on epithelial cells, in vitro and in vivo, and has been shown to accelerate wound healing in several experimental animal models. A randomized, double‐blind, parallel‐group, placebo‐controlled, multicenter study was conducted to evaluate the safety and efficacy of topical repifermin treatment, for 12 weeks, in the healing of chronic venous ulcers in 94 patients. Repifermin was shown to accelerate wound healing, with significantly more patients achieving 75% wound closure with repifermin than with placebo. The treatment effect appeared more marked for a subgroup of patients with initial wound areas ≤ 15 cm2 and wound ages of ≤ 18 months. A longer duration of treatment (e.g., 26 weeks) may allow better differentiation of the benefit of repifermin compared with placebo, particularly with respect to complete wound closure. The safety assessment showed that repifermin was well tolerated.
Maggot versus conservative debridement therapy for the treatment of pressure ulcers
Authors: Sherman Ronald A.
Published: March 2003

To define the efficacy and safety of maggot therapy, a cohort of 103 inpatients with 145 pressure ulcers was evaluated. Sixty‐one ulcers in 50 patients received maggot therapy at some point during their monitored course; 84 ulcers in 70 patients did not. Debridement and wound healing could be quantified for 43 maggot‐treated wounds and 49 conventionally treated wounds. Eighty percent of maggot‐treated wounds were completely debrided, while only 48% of wounds were completely debrided with conventional therapy alone (p=0.021). Within 3 weeks, maggot‐treated wounds contained one‐third the necrotic tissue (p=0.05) and twice the granulation tissue (p < 0.001), compared to non‐maggot‐treated wounds. Of the 31 measurable maggot‐treated wounds monitored initially during conventional therapy, necrotic tissue decreased 0.2 cm2 per week during conventional therapy, while total wound area increased 1.2 cm2 per week. During maggot therapy, necrotic tissue decreased 0.8 cm2 per week (p=0.003) and total wound surface area decreased 1.2 cm2 per week (p=0.001). Maggot therapy was more effective and efficient in debriding chronic pressure ulcers than were the conventional treatments prescribed. Patients readily accepted maggot therapy, and adverse events were uncommon. (WOUND REP REG 2002;10:–214)
Stability analysis of invariant points using Euler spheres, with an application to FMAS granulites
Authors: Kletetschka  , Stout
Published: March 2003

Alternative assignment of invariant point stabilities in a possible P–T  phase diagram is given by a family of grids that derives from a form of the Euler equation. Invariant points are represented by great circles that divide the surface of a sphere (the Euler sphere) into polygonal regions that correspond to the number of potential solutions or grids in n‐component systems with n+3 non‐degenerate phases. A particular invariant point is stable in all grids on one side of the great circle and metastable on the other. The advantage of this representation is the ease and efficiency by which all grids consistent with experimental and theoretical constraints can be identified. The method is well suited for systems of n+3 phases in which the thermochemical data necessary for direct calculation of the phase diagram is either uncertain or non‐existent for one or more of the phases. The mass balance equations among the n+3 phases of interest define the Euler sphere for any particular system. There is a unique Euler sphere for unary systems, and another for binary systems. Ternary and quaternary systems have four and 11 different types of Euler spheres, respectively. In the ternary case with six phases, the 16 non‐degenerate chemographies belong to four groups that are associated with the four Euler spheres. An analysis of those groups shows a close relationship between the topologies of the chemographies and the topologies of the grids represented on the Euler sphere. Euler spheres for degenerate chemographies are characterized by a smaller number of spherical polygons. A useful application of the Euler sphere concept is the systematic derivation of possible FMAS petrogenetic grids from subsystem constraints. Assumption of just one stable invariant point in each of MAS and FAS systems is consistent with seven FMAS grids involving cordierite, garnet, hypersthene, quartz, sapphirine, sillimanite and spinel.
SHRIMP U–Pb zircon dating of Grenville‐age events in the western part of the Musgrave Block, central Australia
Authors: White  , Clarke  , Nelson
Published: March 2003

Shrimp U–Pb zircon dating of structurally constrained felsic orthogneiss samples in the western Musgrave Block has been used to delineate discrete magmatic and metamorphic events at c.1300 and c.1200 Ma. The dating of pre‐D1 and post‐D1 felsic orthogneiss constrains D1 to have occurred at 1312±16 to 1324±4 Ma. This is the first geochronological study to identify such a metamorphic and deformation event in the Musgrave Block. D1 was accompanied by a major magmatic event involving the emplacement of voluminous felsic orthogneiss between 1296 and 1324 Ma. Zircon overgrowths on numerous igneous zircon cores give a consistent age of c.1200 Ma, reflecting zircon growth during a second high‐grade metamorphic event (D2). This c.1200 Ma metamorphic event was followed by the intrusion of a c.1190 Ma megacrystic granite. The c.1300 and c.1200 Ma events in the Musgrave Block can be tentatively correlated with metamorphic events in the Albany‐Fraser Orogen, and the Windmill Islands and Bunger Hills in east Antarctica. A major continuous Grenville‐age orogenic belt joining these areas may have represented a plate boundary between the pre‐Rodinian proto‐Australian continent and proto‐Antarctica during the formation of Rodinia in the Mesoproterozoic.
Importance of fracturing during retro‐metamorphism of eclogites
Authors: Straume  , Austrheim
Published: March 2003

Presented textural and petrological data show that the deep to intermediate continental crust may fracture and that microfractures are the locus of fluid and mass transfer necessary for retrograde metamorphism. Kyanite eclogites from Ulsteinvik, Norway, underwent partial retrogression to granulite and amphibolite facies assemblages during near‐isothermal exhumation from depths equivalent to more than 2.0 GPa at temperatures of 700–800 °C. Plagioclase‐bearing assemblages, rich in hydrous phases, formed along margins of eclogite lenses and along mesoscopic fracture systems. Hydrated zones are from 1–50 cm thick, with adjacent wall‐rock eclogite replaced by symplectites. At a low degree of reaction, the secondary minerals in the wall‐rock are found along intra‐ and intergranular microfractures (typically 50–100 μm wide). Minerals filling the microfractures include orthopyroxene–plagioclase–spinel in garnet; plagioclase–sapphirine, plagioclase–corundum and plagioclase–spinel in kyanite; and diopside–plagioclase in omphacite. The microfractures are often arranged en echelon and are connected through microfaults. Releasing bends filled with amphibole and spinel form along microfaults in garnet. The faulting and fracturing caused localized chemical change in garnet: the damage zones close to faults are enriched in FeO and MnO with steep compositional gradients (8 wt% FeO over <20 μm). These FeO‐ and MnO‐enriched zones form wedge‐like structures around the tip of the faults (horsetail structures) and rose‐ or flame‐like structures at sticking points along faults. They may represent examples of stress‐induced chemical transport during fracture propagation. The change from dry to amphibole‐bearing assemblages at the tip of the fracture, and fractures ending in splays of fluid inclusions trails, reflect the involvement of a fluid phase during fracture propagation. This suggests that the ‘dry’ granulite facies retrogression was also driven by fluid infiltration and that metamorphism at depth in collision zones may not be controlled by pressure and temperature alone.
Sub‐ophiolite metamorphic rocks from NW Anatolia, Turkey
Authors: Önen  , Hall
Published: March 2003

The metamorphic rocks from near Kütahya in north‐west Anatolia record different stages in the history of closure of the Neo‐Tethyan İzmir–Ankara–Erzincan ocean. Sub‐ophiolite metamorphic rocks within the Tavşanlı zone are a tectonically composite sequence of quartz–mica schists, amphibole schists, amphibolites and garnet amphibolites. They show increasing metamorphic grade towards the base of the ophiolite. A first metamorphic event, typical of sub‐ophiolite metamorphic sole rocks, was characterized by high‐grade assemblages, and followed by retrograde metamorphism. A second event was marked by a medium‐to high‐pressure overprint of the first‐stage metamorphic assemblages with assemblages indicating a transition between the blueschist and greenschist facies. The chemistry of the sub‐ophiolite metamorphic rocks indicates an ocean island basalt origin, and Ar–Ar dating indicates a high temperature metamorphic event at 93±2 Ma. Counter‐clockwise P–T–t paths recorded by the sub‐ophiolite metamorphic rocks are interpreted to result from intra‐oceanic thrusting during the closure of the İzmir– Ankara–Erzincan ocean, initiating subduction, which formed the high‐temperature assemblages. Further subduction then produced the widespread blueschists of the Tavşanlı zone during the Late Cretaceous. Later cold thrusting obducted the ophiolite (with the metamorphic sole welded to its base), ophiolitic melanges and blueschists onto the Anatolide passive margin in the latest Cretaceous. All these events pre‐date the final Anatolide–Pontide continent–continent collision.
Inverted metamorphism and the Main Central Thrust: field relations and thermobarometric constraints from the Kishtwar Window, NW Indian Himalaya
Authors: Stephenson  , Waters  , Searle
Published: March 2003

Following the early Eocene collision of the Indian and Asian plates, intracontinental subduction occurred along the Main Central Thrust (MCT) zone in the High Himalaya. In the Kishtwar–Zanskar Himalaya, the MCT is a 2 km thick shear zone of high strain, distributed ductile deformation which emplaces the amphibolite facies High Himalayan Crystalline (HHC) unit south‐westwards over the lower greenschist facies Lesser Himalaya. An inverted metamorphic field gradient, mapped from the first appearance of garnet, staurolite and kyanite index minerals, is coincident with the high strain zone. Petrography and garnet zoning profiles indicate that rocks in the lower MCT zone preserve a prograde assemblage, whereas rocks in the HHC unit show retrograde equilibration. Thermobarometric results derived using THERMOCALC indicate a P–T  increase of c. 180 °C and c. 400 MPa across the base of the MCT zone, which is a consequence of the syn‐ to postmetamorphic juxtaposition of M1 kyanite grade rocks of the HHC unit on a cooling path over biotite grade footwall rocks, which subsequently attain their peak (M2) during thrusting. Inclusion thermobarometry from the lower MCT zone reveals that M2 was accompanied by loading, and peak conditions of 537±38 °C and 860±120 MPa were attained. M1 kyanite assemblages in the HHC unit, which have not been overprinted by M2 fibrolitic sillimanite, were not significantly affected by M2, and conditions of equilibration are estimated as 742±53 °C and 960±180 MPa.

There is no evidence for dissipative or downward conductive heating in the MCT zone. Instead, the primary control on the distribution of peak assemblages, represented by the index minerals, is postmetamorphic ductile thrusting in a downward propagating shear zone. Polymetamorphism and diachroneity of equilibration are also important controls on the thermal profile through the MCT zone and HHC unit.
Crustal thickening and ductile extension in the NE Greenland Caledonides: a metamorphic record from anatectic pelites
Authors: Jones K. A. , Strachan R. A.
Published: March 2003

Caledonian orogenesis in NE Greenland resulted from the collision of Laurentia and Baltica during the Ordovician–Silurian. Anatectic pelites within the metasedimentary Smallefjord Sequence record a clockwise P–T  path, the result of early crustal thickening at c. 445–440 Ma and subsequent exhumation of the high‐grade metamorphic core by a combination of ductile extension and tectonic denudation. The early prograde segment of the path followed a shallow, near‐isothermal trajectory and attained a metamorphic peak of c. 9.0–10.0 kbar at >790 and <850 °C. Prograde metamorphism initiated anatexis of pelites in the kyanite stability field and continued with sillimanite stable. Inclusion trails in the garnet cores are textural remnants of early deformation, which occurred either before or during prograde metamorphism. The peak metamorphic conditions are anomalously high in the context of thermal models and P–T  paths for continental collision zones. The additional heat input required to promote migmatization may have been provided by advection as lower crustal high‐pressure rocks and the uppermost mantle were uplifted following lithospheric thinning at an early stage in the orogeny. The prograde path was interrupted by the development of retrograde extensional shear fabrics defined by biotite+sillimanite and associated with garnet breakdown. Field observations indicate that ductile extension was accompanied by melt extraction, transport and emplacement of intracrustal granites dated at c. 430 Ma. Regional ductile extension and exhumation probably resulted from the development of gravitational instabilities within the overthickened crust during continental collision.