bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual development in infants and young children with Down's syndrome
Authors: Woodhouse J. Margaret , Pakeman Valerie H. , Parker Margaret , Cregg Mary , Fraser William I. , Lobo Sandra , Sastry Prema
Published: March 2003

Purpose: Ocular and refractive defects are common amongst people with Down's syndrome. We are conducting a long‐term study of the development of refraction, accommodation and acuity in infants with Down's syndrome, from 12 weeks of age, in order to identify age of onset and possible consequences of such defects.

Methods: To date, 54 children have entered the study. All measurements are made during home visits, and comprise Mohindra and dynamic retinoscopy, and Preferential Looking.

Results: Cross‐sectional data suggest that acuity lies within normal ranges in infancy, and falls behind the norms only from the age of 2 years. Refractive errors in the general population decrease in infancy (the process of emmetropisation). Our data show that the opposite happens in children with Down's syndrome. The prevalence of refractive errors is higher in the preschool and school‐age children, than amongst the infants. Accommodation is defective from the earliest age of testing. Infants and young children with Down's syndrome consistently under‐accommodate to near targets, even when visual acuity and refractive errors are normal.

Conclusions: The implication of accommodative dysfunction on emmetropisation is considered, and the possible association between visual and cognitive development explored.
The effect of abnormal eye movements upon visual acuity
Authors: Simmers Anita J. , Gray Lyle S. , Winn Barry
Published: March 2003

Purpose: Abnormal fixational eye movements such as those which occur in nystagmus can have a deleterious effect upon visual acuity measurement which is difficult to determine. The repeat letter format of the Regan Repeat Letter charts (RRL) is designed to measure visual acuity independently of abnormal eye movements, and should give higher visual acuity scores than linear test charts in subjects with fixational instability. In the present study RRL and Glasgow Acuity Cards (GAC) were used to determine visual acuity losses arising from fixational instability.

Methods: Monocular visual acuity was measured in five subjects with congenital nystagmus using both GAC and RRL while eye movements were continuously recorded using an infrared limbal reflection eyetracker.

Results: Mean visual acuity obtained with RRL was significantly higher (P < 0.01) than that obtained with GAC. A significant correlation (P < 0.01) was observed between the amplitude of the nystagmus and the visual acuity obtained using GAC. There was no significant correlation between the amplitude of the nystagmus and visual acuity measured using RRL.

Conclusions: The results show that RRL can measure visual acuity independently of abnormal fixational eye movements. Fixational instability in nystagmus is a limiting factor in visual acuity measurements obtained using a linear test chart format.
Binocular vision in interceptive timing
Authors: Mon‐Williams Mark , Wann John P. , Rushton Simon
Published: March 2003

Time to contact of an approaching object may be specified through monocular optic expansion, e.g. ‘tau’ (Lee, 1976). On the other hand it has been demonstrated that disturbing binocular information impairs performance in a dynamic interceptive task (Judge and Bradford, 1988).

Three optical devices were employed to explore whether participants (n = 5) could be trained to utilise different information when estimating time to contact of an approaching ball. A pendulum was used to project a ball at three different velocities. Performance was measured using an IR‐based tracking system (Selspot), and an IR eye‐tracker (Ober2) was used to monitor vergence. Cyclopean spectacles (which remove disparity information) were used to train participants. Pre‐ and post‐training performance was compared with performance in telestereoscopes (these double binocular disparity at near), and spectacles that control for secondary optical effects by increasing the optical pathlength and reducing the field of view and illumination.

Our results confirm that disrupting binocular information impairs performance but that performance quickly recovers. Reasons for the performance recovery will be discussed in relation to the use of available optical information.
The analysis of the transient PERGs to contrast variation
Authors: Lu W. , Harding G. F. A.
Published: March 2003

Black and white checkerboards (56′) of varying contrast levels were presented in the transient reversal mode (2 Hz). The transient Pattern Electroretinograms were recorded on four subjects with normal vision using DTL fibres. Across the contrast range 9–80%, the amplitudes of the response were linearly sensitive to contrast variation without saturation (P < 0.001). Two potentials on the major negative potential (N95) divided by a notch had different contrast sensitivities and contrast gains: the potential after the notch (a‐Nw) was strikingly less sensitive to contrast variation and had a lower contrast gain than the potential before the notch (Nw). a‐Nw had a linearity at contrast level over 23%. Nw showed a high similarity to P50 in both contrast versus amplitude function and contrast gain.

The evident difference of the contrast gains between Nw and a‐Nw suggests that there are possibly some corresponding differences in their retinal origins. It is assumed that the major negative potential after the notch is functioned by the inner retinal neurones with low contrast sensitivity, which includes the ganglion cells, being possibly predominated by the retinal magnocellular cells; the potential Nw has some common retinal mechanisms with P50, probably representing the macular function.
Could a cycloplegic agent be replaced by a fogging or a corrective lens in the biometric measurement of the crystalline lens?
Authors: Kee C. S. , Do Tony C. W. , Lai Ricky Y. K. , Wong G. , Lam Andrew K. C.
Published: March 2003

This study investigated whether a fogging or a corrective lens could be used to replace a cycloplegic agent in the ultrasonic measurement of crystalline lens thickness in myopia. A group of 28 Hong Kong Chinese adults with myopia was recruited. The crystalline lens thickness of the examined eye was measured by A‐scan ultrasonography while the fixating eye was in one of three conditions: fog (+2.00 D fogging lens), full corrective lens, or cycloplegia (50 minutes after instillation of 1% cyclopentolate HCl). We found that the mean lens thickness was significantly different between the three conditions in our myopic subjects. The mean crystalline lens thickness under fogging and corrective lens conditions was significantly greater than the cycloplegic condition by 0.09 mm and 0.11 mm, respectively. The 95% limits of agreement compared to cycloplegia (fogging: −0.32 to +0.14; corrective: −0.35 to +0.13) showed marked intersubject variability, indicating that there is a risk of overestimating the lens thickness when substituting cycloplegia with either a fogging or a corrective lens.
Optometric function in visually sensitive migraine before and after treatment with tinted spectacles
Authors: Evans B. J. W. , Patel R. , Wilkins A. J.
Published: March 2003

Optometrists frequently encounter patients with migraine and patients and practitioners sometimes suspect that visual stimuli or visual anomalies trigger headaches. There is a lack of evidence‐based research on the issue, however. Some patients with migraine may be hypersensitive to visual stimuli, and it has been suggested that individually prescribed coloured filters might be an effective treatment to reduce symptoms from such stimuli. A recent randomised controlled trial showed such a treatment to be effective and the present paper reports on the optometric characteristics of the patients in this study. Twenty‐one patients with neurologically diagnosed migraine were compared with 11 controls. No significant differences were found between the two groups with respect to refractive error, ocular pathology, colour vision, contrast sensitivity, accommodative function, strabismus and hyperphoria. The migraine group tended to be a little more exophoric, but by most criteria they were able to compensate for their exophoria as well as the control group. The migraine group were more prone to pattern glare than the controls (p=0.004). The effects of precision tinted and control tinted lenses were investigated. The only variable to show a consistent and marked improvement with tinted lenses was pattern glare. The most likely mechanism for the benefit from individually prescribed coloured filters in migraine is the alleviation of cortical hyperexcitability (Wilkins et al. 1994) and associated pattern glare.
Normal values and standard deviations for pupil diameter and interpupillary distance in subjects aged 1 month to 19 years
Authors: MacLachlan Colleen , Howland Howard C.
Published: March 2003

Normal values of pupil diameters and interpupillary distances (PDs) were measured in a population of 1311 subjects (in 4294 visits) ranging from 1 month of age to slightly over 19 years of age. Subjects in this study were recruited from birth announcements in a local newspaper for a developmental vision project. Pupil sizes were measured photographically when the corneas were illuminated by 15.9 ± 0.5 lux ambient illumination (i.e. under mesopic conditions). Interpupillary distance was measured with an interocular distance rule while the subject fixated an object at 0.66 m distance. These PD measurements were corrected for systematic measurement errors and to an infinite viewing distance using radii of ocular rotation based on age‐dependent axial lengths. Means and S.D. were calculated for age, pupil diameter and PD for each 1‐year group of male and female subjects. The second order regression equation for average pupil size as a function of age was determined: [males pupil diameter (in mm)=5.83 + 0.181*age in years – 0053*age in years2, r2=0.897; female pupil diameter=5.40 + 0.285*age in years – 0.0109*age in years2, r2=0.945]. The difference between male and female pupil sizes (mean male – female=0.13 mm) was marginally not significant (p < 0.054). The average corrected PDs as a function of age were found to approximate another second‐order regression equation: (males PD=43.36 + 1.663*age in years – 0.034*age in years2, r2=0.986; females PD=41.76 + 1.891*age in years – 0.052*age in years2, r2=0.986). Male PD was wider than female PD by an average of 1.58 mm (p < 0.0003). As expected, the results of this study were similar to a preliminary investigation conducted by Thunyalukul et al. [Invest. Ophthalmol. Vis. Sci.37 (1996) S731] on a portion of the present data set, and also very similar to data from another study of comparable racial composition using a different measurement method [Pryor, Pediatrics44 (1969) 973]. It was concluded that pupil diameter and PD increase more gradually than axial length of the eye in the first few years of life. The normal values and S.D. for both pupil size and PD determined in this study have important clinical implications as well as applications in the optical industry.
Relationship between intraocular pressure and eye growth in chick
Authors: Schmid Katrina L. , Hills Tracy , Abbott Meredith , Humphries Michelle , Pyne Kylie , Wildsoet Christine F.
Published: March 2003

In infants, abnormally high intraocular pressure (IOP) results in excessive eye enlargement. In the study reported here, we investigated whether IOP might be a determinant of ocular elongation using the chick as an animal model. Specifically, we examined IOP changes in (I) normally developing eyes, and (II) eyes undergoing altered growth. In the first case (I), developmental changes in IOP, axial length and refractive error were assessed at approximately daily intervals during early development (days 2–11 post‐hatch, n = 8), and at weekly intervals from weeks 1 to 6 (n = 8). In the second case (II), opposite ocular growth responses were elicited using −15 D and +15 D defocusing spectacle lenses fitted monocularly to 8‐day‐old chicks (n = 8 and 7, respectively). Treated eyes were measured 3 and 7 h after lens application (between 9 and 10 am), as well as 1, 2 and 4 days later, around the same time as the initial lens application. In normal development (I), IOP increased over the first post‐hatch week, peaking at 18.0 ± 5.1 mmHg, and declined slowly thereafter to be back to near ‘hatching’ values at 6 weeks (12.7 ± 5.3 mmHg at day 2 cf. 13.4 ± 1.9 mmHg). Eyes elongated at an approximately linear rate over the entire monitoring period. The −15 D and +15 D lenses (II) produced opposing effects on eye growth, as indicated by axial length changes of + 0.67 ± 0.25 mm cf. −0.33 ± 0.17 mm over the 4‐day treatment period. Both groups showed decreases in IOP over the first 20 h of lens wear. The faster growing eyes of the −15 D group exhibited a later relative increase in IOP. The described changes in IOP are compatible with, but do not prove, a modulatory influence of IOP on early eye growth.
Vitamin K: A Practical Guide to the Dietary Management of Patients on Warfarin
Authors: Booth Sarah L. , Summa Maria A.
Published: March 2003

Warfarin has been successfully used in the medical management of thromboembolic disease for nearly six decades. It is widely assumed that a dietary vitamin K–warfarin interaction exists. To avoid this potential interaction, patients typically receive instructions to consume a constant dietary intake of vitamin K, and sufficient data exist to suggest that a constant dietary intake of vitamin K that meets current dietary recommendations of 65 to 80 mg/day is the most acceptable practice for patients on warfarin therapy. Data concerning the vitamin K content of commonly consumed foods, however, are not readily accessible to clinicians and patients. An understanding of the dietary vitamin K‐warfarin interaction, and dietary sources and usual intakes of vitamin K may facilitate successful anticoagulation for patients being treated with warfarin. ▪

Key Words:
vitamin K, warfarin, anticoagulant phylliquinone
Nutritional Management of Patients with Liver Diseases
Authors: Hébuterne Xavier , Schneider Stéphane Michel
Published: March 2003

Abstract Because the liver is a key metabolic organ, malnutrition is a common finding in patients with cirrhosis. Almost 40 to 50% of these patients are malnourished, and it has been demonstrated that malnutrition independently contributes to morbidity and mortality. Because of liver insufficiency and hyperhydration, most of the common methods of assessment of nutrition status are not useful in patients with liver disease. However, measurement of triceps skinfold and midarm muscle circumference are considered reasonably accurate for the determination of nutrition status in these patients. In cirrhotic patients, energy and protein intake should be no less than 35 kcal/kg of dry body weight/day and 1.2 g/kg/day, respectively. In the case of portal‐systemic encephalopathy, substitution of branched‐chain amino acids for standard amino acid mixtures may be beneficial. When clinically relevant malnutrition occurs, several studies have demonstrated that enteral nutrition is safe and able to favorably influence the outcome.
Nutrition in the Care of the Cancer Patient
Authors: Mutlu Ece A. , Mobarhan Sohrab
Published: March 2003

Proper nutrition care is essential to help prevent or minimize the deleterious effects of cancer, namely malnutrition and cachexia, on nutrition status. When designing appropriate nutrition support, clinicians should consider a patient's history and clinical state including extent of the disease, expected survival, psychological status, and current lifestyle. Oral nutrition is often the preferred means of feeding, but may be limited by factors related to the cancer, the treatment, and the psychologic issues surrounding this disease. Several strategies have been recommended to help patients achieve an adequate oral intake in the presence of anorexia. However, for patients who are severely malnourished or unable to consistently consume more than 75% of their energy needs, enteral nutrition may be indicated. Parenteral nutrition is appropriate only for certain subsets of cancer patients. Numerous trials have shown that use of the enteral route gives comparable results to the parenteral route and is associated with fewer complications and lower costs in both cancer and noncancer patients. There has been much recent interest in the use of immunotherapy—arginine, essential fatty acids, and glutamine—to improve the nutritional status of patients with cancer.
Exercise and HIV Infection
Authors: Roubenoff Ronenn
Published: March 2003

HIV infection is characterized by two opposing macronutrient problems: wasting and lipodystrophy. Wasting is defined as the unintentional loss of 10% or more of body weight. Lipodystrophy is the loss of subcutanous fat in the legs, arms, and face, with increased deposition of fat in the abdomen, breasts, and upper back. In both cases, there is evidence that a judicious diet and exercise can help to reverse or ameliorate these abnormalities. This brief review outlines the current evidence that resistance exercise can be used to treat wasting, and that combined aerobic and resistance exercise can reduce abdominal fat gain in lipodystrophy.
Stages of Change in Clinical Nutrition Practice
Authors: Molaison Elaine Fontenot
Published: March 2003

For years, nutritionists have developed education materials that attempted to change dietary behaviors. However, most of these programs were effective only in increasing knowledge and did not produce long‐term behavior change. Research indicates that nutrition interventions will be more effective if based on a theoretical model. The stages of change theory attempts to explain behavior change as a series of levels of readiness to change. The stages range from precontemplation, where an individual does not recognize the need for change, to the maintenance of long‐term behavior change. Use of this theory in nutrition education has been found to be most effective if education methods are stage specific and address the individual needs of clients. Unfortunately, little research has been done using this theory in traditional clinical nutrition practice, but implementation may be easy for the nutritionist and may help to increase compliance with dietary recommendations in individuals with chronic disease. The first step in using the stages of change theory is to determine the behavior that is going to be changed. With this information, the clinician can then determine the patient's stage of readiness to change a variety of dietary habits. Through the identification of an individual's stage, education methods can be tailored to meet the needs of the patient, helping to promote life‐long dietary change.
Functions of hyaluronan in wound repair
Authors: CHEN W. Y. JOHN , ABATANGELO GIOVANNI
Published: March 2003

Hyaluronan is a major carbohydrate component of the extracellular matrix and can be found in skin, joints, eyes and most other organs and tissues. It has a simple, repeated disaccharide linear copolymer structure that is completely conserved throughout a large span of the evolutionary tree, indicating a fundamental biological importance. Amongst extracellular matrix molecules, it has unique hygroscopic, rheological and viscoelastic properties. Hyaluronan binds to many other extracellular matrix molecules, binds specifically to cell bodies through cell surface receptors, and has a unique mode of synthesis in which the molecule is extruded immediately into the extracellular space upon formation. Through its complex interactions with matrix components and cells, hyaluronan has multifaceted roles in biology utilizing both its physicochemical and biological properties. These biological roles range from a purely structural function in the extracellular matrix to developmental regulation through effects of cellular behavior via control of the tissue macro‐ and microenvironments, as well as through direct receptor mediated effects on gene expression. Hyaluronan is also thought to have important biological roles in skin wound healing, by virtue of its presence in high amounts in skin. Hyaluronan content in skin is further elevated transiently in granulation tissue during the wound healing process. In this review, the general physicochemical and biological properties of hyaluronan, and how these properties may be utilized in the various processes of wound healing: inflammation, granulation and reepithelization, are presented.
A bilayered living skin construct (APLIGRAF®) accelerates complete closure of hard‐to‐heal venous ulcers
Authors: Falanga Vincent , Sabolinski Michael
Published: March 2003

The efficacy of a bilayered, living skin construct (APLIGRAF®[Graftskin]) was evaluated in patients (n = 120) with hard‐ to‐heal venous leg ulcers of greater than 1 year's duration. The study was prospective, randomized, and controlled. Patients received Graftskin plus compression therapy, or standard compression therapy (active control). Patients were evaluated for frequency and time to complete (100%) wound closure. Treatment with Graftskin was significantly more effective than active control in the percentage of patients healed by 6 months (47% vs. 19%; p < 0.005) and the median time to complete wound closure (p < 0.005). Analysis with multivariate regression methods, adjusting for factors generally thought to influence wound healing (duration, baseline area, depth, location, fibrinous wound bed, and infection), showed that patients treated with Graftskin were twice as likely to achieve complete wound closure by 6 months (p < 0.005), and over 60% more effective in achieving wound closure than active control (p < 0.01). These data indicate that Graftskin is an effective treatment for venous ulcers of greater than 1 year's duration.
A modified culture system for epidermal cells for grafting purposes: an in vitro and in vivo study
Authors: van Dorp Annette G. M. , Verhoeven Mary C. H. , van der Nat–van der Meij Tineke H. , Koerten Henk K. , Ponec Maria
Published: March 2003

A fully differentiated epithelium mimicking the features of native epidermis was obtained in vitro by culturing human or porcine epidermal keratinocytes on polyester filter substrate at the air–liquid interface. In addition, after 2 weeks of culture, hemidesmosome‐like structures were formed along the basal area of the plasma membrane of the basal cells at the cell–filter interface. When grafted onto full‐thickness skin wounds in pigs, the take of cell sheets detached from the filter with dispase was significantly higher (about 70%) in comparison to mechanically detached keratinocytes (about 15%). With dispase‐treated keratinocytes alone, basement membrane formation took place within 7 days postgrafting as judged from the presence of a lamina lucida and positive staining for type IV collagen. Also, numerous hemidesmosomes and anchoring fibrils were observed at the basal cell–“neodermis” interface. The fully differentiated epidermis, generated by culturing keratinocytes at the air–liquid interface and detached from the substrate by dispase‐treatment, is less fragile and easier to handle than epidermal autografts obtained by conventional culturing methods. Detachment by a short dispase‐treatment appeared in our hands the only method for successful and complete epithelial regeneration in full‐thickness wounds.
Oxandrolone, an anabolic steroid, enhances the healing of a cutaneous wound in the rat
Authors: Demling Robert H
Published: March 2003

The effect of the anabolic steroid oxandrolone on the healing rate of a standardized full thickness linear wound on the back of the rat was studied. Oxandrolone was given orally by gavage in peanut oil at a dose of 0.1 mg/kg/day. A placebo powder in peanut oil was given at the same dose to a control group. Parameters monitored were time to complete wound closure, wound hydroxyproline content and tensile strength, as well as histology. We found that wounds closed completely in 12 ± 3 days with oxandrolone, compared to 18 ± 3 days for a placebo, a statistically significant difference. The rate of body weight gain was identical in both groups. Hydroxyproline content of the healed incision site was 23 ± 4 mg/g tissue vs. 17 ± 3 mg/g tissue, while the tensile strength increased to 185 ± 13 g/mm2 vs. 102 ± 18 g/mm2 in the oxandrolone and placebo groups, respectively. Both parameters were significantly increased with the anabolic steroid. Histologic examination showed a wound that contained more mature and densely packed collagen and was also hypercellular with oxandrolone treatment. We conclude that the anabolic steroid oxandrolone significantly enhanced wound healing unrelated to any generalized increase in protein mass as would be reflected in body weight.
Inhibition of tumor necrosis factor‐α attenuates wound breaking strength in rats
Authors: Lee Richard H , Efron David T , Tantry Udaya , Stuelten Christina , Moldawer Lyle L , Abouhamze Amer , Barbul Adrian
Published: March 2003

Exogenous administration of tumor necrosis factor‐α has been shown to both enhance and attenuate cutaneous healing in a dose‐dependent manner. We examined the effects of tumor necrosis factor inhibition in the healing wound by both systemic and local administration of tumor necrosis factor‐binding protein. Male Balb/C mice underwent dorsal skin incision with subcutaneous implantation of 20 mg polyvinyl alcohol sponges (4 per animal). In Experiment I, one group (n= 20) received intraperitoneal injections of tumor necrosis factor‐binding protein (3 mg/kg) at the time of wounding, while another group (n= 20) received saline. Four animals from each group were euthanized on days 1, 3, 5, 7, and 14 postwounding. In Experiment II, one group (n= 10) received an intraperitoneal injection of tumor necrosis factor‐binding protein (3 mg/kg) at the time of wounding and every third day thereafter. Another group (n= 10) received an intraperitoneal injection of saline at the time of wounding and every third day thereafter. In Experiment III, one group received a single intraperitoneal injection of tumor necrosis factor‐binding protein (3 mg/kg) at the time of wounding (n= 7), or on postwounding day 4 (n= 7), or day 7 (n= 7). Another group received saline injections at the time of wounding (n= 7), or on postwounding days 4 or 7 (n= 7, respectively). All animals in Experiments II and III were killed at postwounding day 14. Wound breaking strengths were assessed using a tensiometer. Wound fluid collected from the implanted sponges was assayed for tumor necrosis factor‐α and tumor necrosis factor‐binding protein levels using a biological assay and enzyme‐linked immunosorbent assay, respectively. Collagen gene expression in sponge granulomata was assessed by Northern analysis. Collagen deposition in sponges was quantified by measuring hydroxyproline content. Wounds were significantly weaker in the animals that received repeated injections of tumor necrosis factor‐binding protein with a mean wound breaking strength of 93.1 g vs. 186.6 g in controls (p < 0.05). Wound breaking strength in groups that received a single injection of tumor necrosis factor‐binding protein on either day 0, 4, or 7 postwounding were no different than their respective controls. There was no difference in the mean hydroxyproline content of sponges between any of the tumor necrosis factor‐binding protein groups and their respective controls. Northern analysis for collagen I and III expression also revealed no differences. These data indicate that continued systemic administration of tumor necrosis factor‐binding protein resulted in significantly weaker wounds with no corresponding differences in wound collagen content, and collagen gene expression. This suggests that tumor necrosis factor‐α inhibition throughout healing leads to a qualitatively impaired wound without a quantitative alteration in collagen deposition.
EFFECTS OF ELECTRICAL STIMULATION ON THE HISTOLOGICAL PROPERTIES OF WOUNDS IN DIABETIC MICE
Authors: Thawer Habiba A , Houghton Pamela E
Published: March 2003

The purpose of this study was to identify mechanisms underlying electrically stimulated wound closure in diabetic mice. Adult male mice (n= 58) with full‐thickness excisional wounds were treated five times using negative polarity over the wound site for 15 minutes each over a 16‐day period with sham (0 Volts) or 5.0, 10.0, 12.5 Volts. In addition, animals (diabetic [n= 33] and nondiabetic [n= 22]) received treatments of electrical stimulation (12.5 V), or sham treatment (0 V) at wound sites which were then harvested and prepared for histological analysis at 2, 8, and 16 days postwounding. Using computerized image analysis of sections stained with a picro sirus red‐fast green staining technique, we found that increasing doses of electrical stimulation reduced collagen/noncollagenous protein ratios measured in the superficial scar of nondiabetic animals, with no effect in diabetic animals. In the deep scar, lower doses of electrical stimulation (5.0 V) produced significantly (p < 0.01) increased collagen deposition in wounds of nondiabetic animals compared with sham controls. Higher doses of electrical stimulation (12.5 V) were required to produce changes in diabetic animals than were observed in nondiabetic animals. These results suggest that electrical stimulation altered collagen deposition in excisional wounds of diabetic and nondiabetic animals. Electrical stimulation had a differential effect on wound healing in diabetic compared with nondiabetic animals. These data speak to the need to study the effects of electrical stimulation on healing in disease‐specific models.
Hyaluronic acid in incision wound fluid: A clinical study with the Cellstick® device in children
Authors: Pajulo Olli T. , Pulkki Kari J. , Lertola Kaarlo K. , Alanen Markku S. , Reunanen Mikko S. , Virtanen Riitta V. , Mattila‐Vuori Armi I. , Viljanto Jouko A.
Published: March 2003

When inserted into a human incision wound, the Cellstick® device harvests inflammatory cells and collects wound fluid, reflecting time‐related changes in cell populations and in wound fluid composition. Hyaluronic acid has been postulated to be an important factor in scar reduction in wound healing and in scarless fetal wound healing. The aim of this work was to determine the concentration and variation of hyaluronic acid and proportions of wound cells in closed surgical wounds in children at two time points. The Cellstick® device was inserted subcutaneously into the wound at the end of an elective inguinal hernia operation on 37 healthy boys, and the devices were removed 3±1 or 24±3 hours after surgery. Haluronic acid concentration was measured from the wound fluid and a differential count of the wound cells was performed. There was a significant decrease in hyaluronic acid concentration from 3±1 to 24±3 hours after surgery (p<0.001, Kruskal‐Wallis anova). The variance of hyaluronic acid concentration in wound fluid differed between the wounds at the two time points (p<0.01, Levene test for homogeneity of variance). A positive correlation between hyaluronic acid concentration and patient age (r=0.91, p<0.05, Spearman) at 3±1 hours post surgery and between HA and wound lymphocytes (r=0.38, p<0.05, Spearman) was also found. We conclude that the hyaluronic acid concentration in wound fluid peaks early in children and decreases significantly by 3 to 24 hours after surgery, and the concentrations in the wound fluid of healthy boys are more variable 3 hours than at 24 hours after surgery.
Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma
Authors: AKASAKA YOSHIKIYO , FUJITA KAZUKO , ISHIKAWA YUKIO , ASUWA NORIKO , INUZUKA KIYOSHI , ISHIHARA MOTOKO , ITO MASAMICHI , MASUDA TAKAO , AKISHIMA YURI , ZHANG LIJUN , ITO KINJI , ISHII TOSHIHARU
Published: March 2003

Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and the development of pathological scarring. In this study, we demonstrate that keloid fibroblasts can be identified as apoptotic cells because of their highly condensed chromatin and discrete nuclear fragments. To further reveal the phenomenon of apoptosis, we quantified the number of terminal deoxynucleotide transferase‐mediated dUTP nick‐end labeling (TUNEL)‐positive cells in surgically resected tissues of keloids (N = 10), hypertrophic scars (N = 10), normal healed flat scars (N = 10), and dermatofibroma (N = 10). The number of TUNEL‐positive cells was relatively low, but was significantly higher for the keloid group compared with the normally healed flat scar group (p = 0.004), suggesting reduced cell survival and increased apoptotic cell death in a subpopulation of keloid fibroblasts. Furthermore, the number of TUNEL‐positive cells was significantly higher for the keloid group compared with the dermatofibroma group (p = 0.044), suggesting that a subpopulation of keloid fibroblasts may suppress tumorgenicity at a greater rate than dermatofibroma by undergoing cell death. Hypertrophic scars had significantly higher levels of apoptosis than normally healed flat scars (p = 0.033). Therefore, these results suggest that selected fibroblasts in keloids and hypertrophic scars undergo apoptosis, which may play a role in the process of pathological scarring.
Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing
Authors: Wright J. Barry , Lam Kan , Buret Andre G. , Olson Merle E. , Burrell Robert E.
Published: March 2003

A porcine model of wound healing was employed to examine the impact of nanocrystalline silver–coated dressings on specific wound healing events. Full‐thickness wounds were created on the backs of pigs, contaminated with an experimental inoculum containing Pseudomonas aeruginosa, Fusobacterium sp., and coagulase‐negative staphylococci, and covered with dressing products either containing silver or not. Nanocrystalline silver‐coated dressings promoted rapid wound healing, particularly during the first several days post‐injury. Healing was characterized by rapid development of well vascularized granulation tissue that supported tissue grafting 4 days post‐injury, unlike control dressed wounds. The proteolytic environment of wounds treated with nanocrystalline silver was characterized by reduced levels of matrix metalloproteinases. Matrix metalloproteinases have been shown to be present in chronic ulcers at abnormally high levels, as compared with acute wounds, and may contribute to the nonhealing nature of these wounds. Cellular apoptosis occurred at a higher frequency in the nanocrystalline silver–treated wounds than in wounds dressed with other products. The results suggest that nanocrystalline silver may play a role in altering or compressing the inflammatory events in wounds and facilitating the early phases of wound healing. These benefits are associated with reduced local matrix metalloproteinase levels and enhanced cellular apoptosis. (WOUND REP REG 2002;10:)
The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective analysis of 1144 patients
Authors: Fife Caroline E. , Buyukcakir Cem , Otto Gordon H. , Sheffield Paul J. , Warriner Robert A. , Love Tommy L. , Mader Jon
Published: March 2003

The objective of this retrospective analysis was to determine the reliability of transcutaneous oxygen tension measurement (TcPO2) in predicting outcomes of diabetics who underwent hyperbaric oxygen therapy for lower extremity wounds. Six hyperbaric facilities provided TcPO2 data under several possible conditions: breathing air, breathing oxygen at sea level, and breathing oxygen in the chamber. Overall, 75.6% of the patients improved after hyperbaric oxygen therapy. Baseline sea‐level air TcPO2 identified the degree of tissue hypoxia but had little statistical relationship with outcome prediction because some patients healed after hyperbaric oxygen therapy despite very low prehyperbaric TcPO2 values. Breathing oxygen at sea level was unreliable for predicting failure, but 68% reliable for predicting success after hyperbaric oxygen therapy. TcPO2 measured in chamber provides the best single discriminator between success and failure of hyperbaric oxygen therapy using a cutoff score of 200 mmHg. The reliability of in‐chamber TcPO2 as an isolated measure was 74% with a positive predictive value of 58%. Better results can be obtained by combining information about sea‐level air and in‐chamber oxygen. A sea‐level air TcPO2 < 15 mmHg combined with an in‐chamber TcPO2 < 400 mmHg predicts failure of hyperbaric oxygen therapy with a reliability of 75.8% and a positive predictive value of 73.3%. (WOUND REP REG 2002;10:198–207)
Molecular and cell biology of porcine HSP47 during wound healing: complete cDNA sequence and regulation of gene expression
Authors: Wang Jian Fei , Olson Merle E. , Winkfein Robert J. , Kulyk William M. , Wright J. Barry , Hart David A.
Published: March 2003

Heat shock protein (HSP) 47 is a major stress‐inducible protein that is localized to the endoplasmic reticulum of avian and mammalian cells and is thought to act as a molecular chaperone specific for the processing of procollagen. However, limited information is available regarding the regulation of HSP47 during wound healing. Using a polymerase chain reaction strategy, screening of a cDNA library, and RACE‐polymerase chain reaction approaches, the sequence of a full‐length porcine HSP47 cDNA has been identified. The cDNA contained 2096 bp that encodes for an 18 amino acid signal peptide and a mature protein coding region consisting of 401 amino acid residues. It also included 108 bp of the 5′ noncoding region and a 731‐bp 3′ noncoding region. The deduced amino acid is 83% identical to chicken, 87% identical to mouse, 88% identical to rat, and 91% identical to human HSP47. It also shares between 26% and 30% identity with different members of the serine protease inhibitor superfamily. The protein contains a RDEL endoplasmic reticulum retention signal, and two potential glycosylation sites. All of these features are characteristic of HSP47 in higher vertebrates. Heat shock treatment of porcine fibroblasts led to up‐regulation of HSP47 at both the transcriptional and translational levels. HSP47 protein levels were also up‐regulated during skin wound healing in a pig model. Moreover, a higher molecular weight complex at approximately 140 Kda containing HSP47 was detected at the stage of healing that was coincident with the maximal transcriptional expression of HSP47 during wound healing in this animal model. Further investigation of how HSP47 is regulated during normal and abnormal skin wound healing may lead to new therapeutic approaches to improve the healing process. (WOUND REP REG 2002;10:230–240)
Low‐pressure metamorphism of Palaeozoic pelites in the Aspromonte, southern Calabria: constraints for the thermal evolution in the Calabrian crustal cross‐section during the Hercynian orogeny
Authors: GRAEßNER  , SCHENK
Published: March 2003

During Hercynian low‐pressure/high‐temperature metamorphism of Palaeozoic metasediments of the southern Aspromonte (Calabria), a sequence of metamorphic zones at chlorite, biotite, garnet, staurolite–andalusite and sillimanite–muscovite grade was developed. These metasediments represent the upper part of an exposed tilted cross‐section through the Hercynian continental crust. P–T  information on their metamorphism supplements that already known for the granulite facies lower crust of the section and allows reconstruction of the thermal conditions in the Calabrian crust during the late Hercynian orogenic event.

Three foliations formed during deformation of the metasediments. The peak metamorphic assemblages grew mainly syntectonically (S2) during regional metamorphism, but mineral growth outlasted the deformation. This is in accordance with the textural relationships found in the lower part of the same crustal section exposed in the northern Serre. Pressure conditions recorded for the base of the upper crustal metasediments are c. 2.5 kbar and estimated temperatures range from <350 °C in the chlorite zone, increasing to 500 °C in the lower garnet zone, and reaching 620 °C in the sillimanite–muscovite zone. Geothermal gradients for the peak of metamorphism indicate a much higher value for the upper crust (c. 60 °C km−1) than for the granulite facies lower crust (30–35 °C km−1). The small temperature difference between the base of the upper crust (620 °C at c. 2.5 kbar) and the top of the lower crust (690 °C at 5.5 kbar) can be explained by intrusions of granitoids into the middle crust, which, in this crustal section, took place synchronously with the regional metamorphism at c. 310– 295 Ma.

It is concluded that the thermal structure of the Calabrian crust during the Hercynian orogeny – as it is reflected by peak metamorphic assemblages – was mainly controlled by advective heat input through magmatic intrusions into all levels of the crust.
Sm–Nd evidence for high‐grade Ordovician metamorphism in the Arunta Block, central Australia
Authors: Mawby  , Hand  , Foden
Published: March 2003

Sm–Nd ages from the Harts Range in the south‐eastern Arunta Inlier in central Australia indicate that regional metamorphism up to granulite facies occurred in the Early Ordovician (c. 475 Ma). This represents a radical departure from previous tectonic models for the region and identifies a previously unrecognized intraplate event in central Australia. Peak metamorphic assemblages (800 °C and 10.5 kbar) formed at around 476±14 Ma and underwent approximately 4 kbar of near‐isothermal decompression at 475±4 Ma. A coarse‐grained unfoliated garnet–clinopyroxene‐bearing marble inferred to have recrystallized late in the decompressional evolution, gives an age of 469±7 Ma. Two lines of evidence suggest the Early Ordovician tectonism occurred in an extensional setting. First, the timing of the high‐grade lower crustal deformation coincides with a period of marine sedimentation in the Amadeus and Georgina basins that was associated with a seaway that developed across central Australia. Second, isothermal decompression of lower crustal rocks was associated with the formation of a regional, sub‐horizontal mid‐crustal foliation. In the Entia Gneiss Complex, which forms the structurally lowest part of the Harts Range, upper‐amphibolite facies metamorphism (c. 700 °C, 8–9 kbar) occurred at 479±15 Ma. There is no evidence that P–T conditions in the Entia Gneiss Complex were as high as in the overlying units. This implies that the extensional system was reworked during a later compressional event. Sm–Nd data from the mid‐amphibolite facies (c. 650 °C and 6 kbar) detachment zone that separates the Irindina Supracrustal Assemblage and Entia Gneiss Complex give an age of 449±10 Ma. This age corresponds to the timing of a change in the pattern and style of sedimentation in the Amadeus and Georgina basins, and indicates that the change in basin dynamics was associated with mid‐crustal deformation. It also suggests that compressional deformation culminating in the Devonian to Carboniferous (400–300 Ma) Alice Springs Orogeny may have begun as early as c. 450 Ma. At present, the extent of Early Ordovician tectonism in central Australia is unknown. However, granulite facies metamorphism and associated intense deformation imply an event of regional extent. An implication of this work is that high‐grade lower crustal metamorphism and intense deformation occurred during the development of a broad, shallow, slowly subsiding intraplate basin.
Lithospheric pressure–depth relationship in compressive regions of thickened crust
Authors: Petrini  , Podladchikov
Published: March 2003

We investigate the pressure distribution with depth in regions undergoing horizontal shortening and experiencing crustal thickening both analytically and numerically. Our results show that, in a convergent tectonic setting, pressure can be considerably higher than lithostatic (the pressure resulting from the weight of the overburden). Increases in pressure with respect to lithostatic conditions result from both the contribution of horizontal stresses and the flexural vertical loads, the latter generated by the deflection of the upper crust and of the mantle because of the presence of topographic relief and a root, respectively. The contribution of horizontal stresses is particularly relevant to the upper crust and uppermost mantle, where rocks are thought to deform brittlely. In these domains, pressure gradients twice lithostatic can be achieved. The contribution of horizontal stresses is less important in the ductile domains as differential stresses are progressively relaxed; nevertheless, the effects are still noteworthy especially close to the brittle–ductile transition. Flexural vertical loads generated by the deflection of the upper crust and lithospheric mantle are relevant for rocks of the weaker lower crust. As a result of the combination of the two mechanisms, the pressure gradient varies vertically through the lithosphere, ranging from negative (inverted) gradients to gradients up to several times the lithostatic gradient. The pressure values range from one to two times the lithostatic values (1ρgz to 2ρgz).
Preservation of old U–Th–Pb ages in shielded monazite: example from the Beni Bousera Hercynian kinzigites (Morocco)
Authors: Montel  , Kornprobst  , Vielzeuf
Published: March 2003

Four samples from the metamorphic aureole around the Beni Bousera ultramafic massif were studied in detail for U–Th–Pb electron microprobe dating on monazite. The samples include three meta‐sedimentary granulites (kinzigites), collected at variable distance from the peridotites, and one kyanite‐bearing leucosome in the kinzigite. Two types of monazite were identified in thin section, using SEM. The main population consists of interstitial grains, 20–70 μm in size, while the second population consists of small grains (<20 μm), included in garnet. A total of 64 U–Th–Pb electron microprobe measurements on 53 monazite crystals were undertaken. Most crystals have a Pb content lower than the Pb detection limit, indicating that they crystallized, or were reset, during a young event, probably Cainozoic in age. Few crystals, all entirely included in garnet, have Hercynian age, the best estimate of which is 284±27 Ma. This is a direct demonstration of the shielding effect of garnet for the U–Th–Pb system in monazite. The grains in inclusion in garnet are not reset by the post‐Hercynian events, despite the high temperature reached at this time (>850 °C). Thus, the monazite closure temperature depends on its textural position in the host rock. The data also show that a Hercynian event occurred in the Beni Bousera granulitic metapelites, which equates with a high‐P, high‐T  event. The emplacement of the peridotite in the Cainozoic may be linked a low‐P, high‐T  event, followed by a low‐P, low‐T  retrogression. These two events reset the U–Th–Pb system in almost all monazite grains, except for the few crystals shielded by garnet.