bluuebunny/crossref_metadata_2025 huggingface dataset:
A late defect in wound healing associated with recurrent spontaneous pneumothoraces: a presumptive role for abnormal collagenase activity
Authors: Lindblad William J. , Kolb James E. , Flood Louise C. , Holbrook Karen A. , Cohen I. Kelman , Roland Claude C. , Hoehn James , Judge Timothy , McKneally Martin F.
Published: September 2002

This case report concerns an individual with a defect in wound healing which resulted in recurring, bilateral pneumothoraces during the late postoperative period. This patient had no history of systemic disease or wound healing abnormalities before his recurrent wound disruption. Physical examination and routine biochemical studies failed to identify any causative agent for the multiple wound dehiscences in the patient. Histologic examination of scar tissue showed collagen fiber bundles with a diameter 50% less than that of normal fibrils. Elastic fibers were barely visible, and the scar tissue included a large number of inflammatory cells. A significant finding was an elevated and aberrant expression of collagenase by a fibroblast cell line established from a skin biopsy specimen. This enhanced level of collagenase expression could be inhibited by treatment of the cells with diphenylhydantoin, an inhibitor of collagenase biosynthesis. After initiation of diphenylhydantoin therapy, the patient's scar formation normalized with the recurrent pneumothoraces. These findings support the conclusion that an abnormal expression of collagenase resulted in enhanced degradation of collagen in the patient's wounds, thereby leading to wound dehiscence.
Fibroblast heterogeneity in the healing wound
Authors: Sempowski Gregory D. , Borrello Melinda A. , Blieden Timothy M. , Barth Richard K. , Phipps Richard P.
Published: September 2002

Although fibroblasts are traditionally described as static cells providing framework and support for tissues, there is an accumulating body of evidence showing that fibroblasts are a dynamic cell type which exist in functionally and morphologically heterogeneous subpopulations. Fibroblast subsets have been shown to play a critical role in the production and regulation of extracellular matrix components, in wound repair and regeneration, and have been implicated in the pathogenesis of fibrotic conditions. We have reviewed the evidence supporting heterogeneity of fibroblasts from pulmonary, periodontal, and dermal tissues. In addition, we will explore the role fibroblast subpopulations may play in the complex process of wound repair and regeneration.
Spatial and temporal expression of transforming growth factor‐β isoforms during ovine excisional and incisional wound repair
Authors: McMullen Heather , Longaker Michael T. , Cabrera Raphael C. , Sung Joanne , Canete John , Siebert John W. , Lorenz H. Peter , Gold Leslie I.
Published: September 2002

To elucidate the role for transforming growth factor‐β isoforms (β1, ‐β2, and ‐β3) in wound repair, we used isoform‐specific antibodies to detect the spatial and temporal expression of the latent and mature/active transforming growth factor‐β isoforms by immunohistochemical localization through 21 days after excisional and incisional wounding of ovine skin. Although incisional and excisional wounds showed similar patterns of transforming growth factor‐β immunoreactivity, we found a differential temporal and spatial expression of the latent and mature transforming growth factor‐β isoforms throughout wound repair. Specifically, 1 day after wounding, there was a marked increase in transforming growth factor‐β isoforms in the epithelium adjacent to the wound, epidermal appendages, and the cells and matrix of the granulation tissue. At this time, transforming growth factor‐β3 isoform was the most abundant. Most notably, the epidermis adjacent to the wound was intensely immunoreactive for all transforming growth factor‐β isoforms 1 day after injury. However, the migrating epithelium, derived from both the hair follicles and the wound margins, was completely devoid of immunoreactive transforming growth factor‐β until reepithelialization was complete. Within the inflammatory exudate, there was a distinct band of leukocytes that was immunoreactive for transforming growth factor‐β2 and ‐β3 1 day after injury and 1 day later for transforming growth factor‐β1. Although transforming growth factor‐β1 and ‐β2, latent transforming growth factor‐β2, transforming growth factor‐β3, and latent transforming growth factor‐β3 immunostaining was present in the numerous fibroblasts and other dermal cells, latent transforming growth factor‐β1 was only associated with the extracellular matrix. In general, immunoreactivity remained high until day 7 after wounding and slowly subsided over time. However, by day 21, immunostaining had not returned to normal and the original wound was replete with immunoreactive fibroblasts and a dense, immunostained extracellular matrix. Thus, although the dynamic presence of transforming growth factor‐β isoforms exemplifies its positive role in the wound repair process, its persistence together with its known potent effects on matrix accumulation, supports its role in scar formation.
Differential regulation of collagen gene expression in granulation tissue and nonrepair connective tissues in vitamin C‐deficient guinea pigs
Authors: Kipp Deborah , Wilson Shirley , Gosiewska Anna , Peterkofsky Beverly
Published: September 2002

Poor wound healing during vitamin C deficiency is thought to be due to decreased hydroxylation of proline residues in collagen. In nonrepair connective tissues of guinea pigs, however, procollagen gene expression is not decreased until weight loss occurs during the third and fourth weeks of scurvy (phase II) with only a moderate decrease in proline hydroxylation. Decreased procollagen gene expression is related to the induction of insulin‐like growth factor binding proteins 1 and 2 that inhibit insulin‐like growth factor‐I action. We examined wound healing and granulation tissue formation during phase I of vitamin C deficiency. Synthetic sponges were implanted on day 7 of vitamin C deficiency and analyzed at 6 and 10 days after surgery, when there was no weight loss or induction of insulin‐like growth factor binding proteins. Healing of incisions was almost complete at 10 days after surgery in normal controls but not in scorbutic animals. The area around the incision and implant exhibited excessive angiogenesis and hemorrhaging of vessels in the scorbutic animals at 6 and 10 days after surgery. At 10 days after surgery, collagen synthesis in the implants of scorbutic guinea pigs was 36% lower than control values, with a normal extent of proline hydroxylation. Concentrations of messenger RNAs for types I and III procollagens were slightly increased by scurvy at 6 days after surgery but were decreased by 26% and 40%, respectively, at 10 days. Fibronectin mRNA levels were unaffected by scurvy at both time points. Our results suggest that poor wound healing in phase I of scurvy may be related to defective interstitial procollagen gene expression and defective blood vessel formation, but it does not involve inhibition of proline hydroxylation or induction of insulin‐like growth factor binding proteins. mRNA for insulin‐like growth factor‐II, transforming growth factor‐β1, and transforming growth factor‐β2 were significantly expressed in implants, but their patterns of expression did not correlate with changes in procollagen gene expression.
Altered collagen metabolism and delayed healing in a novel model of ischemic wounds
Authors: Schwarz Daniel A. , Lindblad William J. , Rees Riley S.
Published: September 2002

Cellular mechanisms occurring in the healing wound have been well described in various animal models. However, the events associated with wound healing seen in ischemic skin have not been as thoroughly defined. In this series of experiments, we created a novel model of excisional skin wounds under gradient ischemia to study the cellular and extracellular events leading to delayed healing. We hypothesized that altered collagen metabolism accounts for delayed wound healing in ischemic skin. Three pairs of 4 mm punch wounds were made 4 days after bipedicle skin flaps were created on the dorsum of rats. Sham‐operated control animals had the same punch wounds without flap creation. The kinetics of excisional wound healing were measured by means of computerized planimetry. In addition, wounds were excised with a 6 mm trephine, radiolabelled with (3H)‐proline and in vitro collagen synthesis determined as collagenase digestible protein along with quantitation of DNA content. Total collagen deposition was determined as 4‐hydroxy‐L‐proline by high‐performance liquid chromatography, and wounds were histologically evaluated. Data was analyzed by means of two‐way analysis of variance. Although control wounds healed by day 10, flap wounds consistently had greater surface area on days 2, 4, 6, 8, and 12 (p < 0.001). Relative collagen synthesis (% collagen/noncollagen protein), as measured by an in vitro synthesis method, showed no statistically significant differences between flap and controls wounds. However, the total collagen content (deposition) as measured by 4‐hydroxy‐l‐proline was significantly lower in flap wounds compared with controls on days 7 (p < 0.05) and 9 (p < 0.001). In addition, a significant increase occurred in DNA content in the flap wounds on days 7 (p < 0.05) and 9 (p < 0.001) versus control wounds. These data indicate that, in ischemic wounds, significantly less collagen is deposited despite the inherent ability of the tissue to synthesize appropriate levels of collagen. Because the in vitro collagen synthesis technique only assesses the ability of the tissue to synthesize collagen in a well oxygenated environment, one cannot be assured that the tissue expresses this potential in vivo. However, these data are consistent with the hypothesis that the delay in wound closure is due to an alteration in collagen metabolism which results in a net decrease in collagen accumulation. Because of the observed increase in DNA within the ischemic wounds, we suggest that there is prolonged inflammation in these wounds which may enhance collagen degradation through the release of proteases. In addition, there may be an inability of the tissue to maintain appropriate levels of collagen in this inflammatory wound environment.
Hyaluronan, heterogeneity, and healing: The effects of ultrapure hyaluronan of defined molecular size on the repair of full‐thickness pig skin wounds
Authors: Arnold Frank , Jia Chiyu , He Chufa , Cherry George W. , Carbow Birgit , Meyer‐Ingold Wolfgang , Bader Dan , West David C.
Published: September 2002

The extracellular matrix macromolecule, hyaluronan, is thought to modulate wound healing. However, the molecular size of hyaluronan and contaminating associated proteins may be important determinants of these effects. We have examined the results of seven daily topical treatments of full‐thickness skin wounds in pigs with ultrapure hyaluronan of defined molecular size. High molecular weight hyaluronan (>1000 kd) enhanced, whereas low molecular weight hyaluronan decreased, the rate of early wound contraction as compared with intermediate hyaluronan (molecular weight = 100 kd) and saline solution controls. Fracture strength at 21 days was reduced by high and intermediate molecular weight hyaluronan but not by low molecular weight hyaluronan. Wound perfusion, measured by means of a scanning laser‐Doppler technique as a noninvasive indicator of angiogenesis, showed depression by high and intermediate molecular weight hyaluronan on day 3, but all forms of hyaluronan caused elevated blood flow on day 7. The architecture of granulation tissue in this wet healing model was highly organized, but no gross histologic differences were seen because of treatment. Different molecular species of hyaluronan have differential effects on contraction, angiogenesis, and the evolution of wound strength. Where hyaluronan is used as a treatment or vehicle for wounds, its precise composition should be specified.
Combination of platelet‐derived growth factor‐BB and insulin‐like growth factor‐I is more effective than platelet‐derived growth factor‐BB alone in stimulating complete healing of full‐thickness wounds in “older” diabetic mice
Authors: Kiritsy Christopher P. , Antoniades Harry N. , Carlson Mark R. , Beaulieu Michelle T. , D'Andrea Mark , Lynch Samuel E.
Published: September 2002

Platelet‐derived growth factor and insulin‐like growth factor‐I have been shown to interact synergistically to enhance repair of skin wounds in normal healing swine. Platelet‐derived growth factor alone has shown promise in treating human chronic ulcers. The objective of this study was to compare the wound healing effects of platelet‐derived growth factor‐BB alone with those of a combination of platelet‐derived growth factor‐BB and insulin‐like growth factor‐I in an improved model with the use of “older” animals with diabetes. Older diabetic (db/db) mice (>15 weeks of age) have less elevated insulin levels compared with young db/db mice. The serum insulin levels in the older animals is 1.0 to 2.5 times that of the nondiabetic animals, a similar increase to that which occurs in human patients with type II diabetes. Healing was evaluated in two studies involving a total of 104 animals. Treatment groups included the following: 4.0 µg/cm2 of platelet‐derived growth factor‐BB, 40.0 µg/cm2 of platelet‐derived growth factor‐BB, 4.0 µg/cm2 of both platelet‐derived growth factor‐BB and insulin‐like growth factor‐I or vehicle. All growth factors were applied topically in a methylcellulose vehicle to full‐thickness wounds every other day for 24 days. Efficacy end points were median and mean time to complete healing and rate of wound closure. The median time to complete healing for animals receiving the platelet‐derived growth factor‐BB/insulin‐like growth factor‐I combination was 38% and 33% faster (p < 0.001) than animals receiving 4.0 µg/cm2 and 40.0 µg/cm2 of platelet‐derived growth factor‐BB, respectively. The mean time to complete healing for platelet‐derived growth factor/insulin‐like growth factor‐I treated animals was 31% and 29% faster (p < 0.001) than 4.0 µg/cm2 and 40.0 µg/cm2 platelet‐derived growth factor‐BB treated animals, respectively. Wounds treated with 4.0 µg/cm2 platelet‐derived growth factor‐BB/insulin‐like growth factor‐I healed, on average, in 22 days compared with 31 days for 40.0 µg/cm2 platelet‐derived growth factor‐BB alone and 38 days for vehicle. Also, platelet‐derived growth factor‐BB/insulin‐like growth factor‐I significantly improved the rate of wound closure throughout the duration of the studies compared with either dose of platelet‐derived growth factor‐BB alone (p < 0.005) or vehicle (p < 0.001). In conclusion, the data show that the combination of platelet‐derived growth factor‐BB and insulin‐like growth factor‐I is more effective than platelet‐derived growth factor‐BB alone at the doses tested or vehicle treatment in stimulating cutaneous wound healing in older, diabetic mice.
Transforming growth factor‐β: activity and efficacy in animal models of wound healing
Authors: Roberts Anita B.
Published: September 2002

Of the myriad of growth factors examined for their ability to accelerate or improve tissue repair, none has as broad a spectrum of action as that of TGF‐β. In the 10 years since the first description of its ability to enhance wound healing, tremendous advances have been made in understanding the basis of its action in tissue repair. It is released from activated platelets and can both act on and be secreted by each of the diverse cell types which participate in the healing process. Actions of TGF‐β to stimulate chemotaxis, fibrogenesis, angiogenesis, and autoinduction of its expression are mediated by signalling through a unique set of serine‐threonine kinase receptors which distinguish it mechanistically from other growth factors with activities in wound healing. Both topical and systemic administration of TGF‐β have been shown to improve healing in a variety of animal models of both normal and impaired healing at dermal as well as nondermal sites such as bone, intestine, the eye, or the mouth.
Increased specific binding of insulin‐like growth factor‐I in healing cutaneous wounds
Authors: Hakim Fares S. , Shetty Shalesh , Sidawy Anton N. , Curcio Lisa D. , Korman Louis Y. , Harmon John W.
Published: September 2002

Insulin‐like growth factor‐I is a polypeptide hormone structurally related to insulin. It is a potent mitogen that promotes growth and differentiation in many tissues. A role for insulin‐like growth factor‐I in wound healing is suggested by its rapid rise in levels and increased insulin‐like growth factor‐I messenger RNA expression in tissue after wounding. We designed our study to characterize possible changes in insulin‐like growth factor‐I receptor binding during wound healing. Surgical wounds created on the abdominal skin of anesthetized New Zealand White rabbits were either left open or closed primarily. Size‐ and weight‐matched specimens were harvested at wounding time (day 0), and at 1, 4, 7, 38, and 50 days after wounding. Preliminary experiments showed that the greatest difference in specific binding occurred between day 0 and day 7. 125I‐insulin‐like growth factor‐I binding studies were performed on frozen tissue specimens and autoradiography was performed and analyzed by computerized densitometry. Scatchard analysis of the binding data showed a single class of insulin‐like growth factor‐I binding sites whose affinity that is, binding constant (Kd = 0.6 × 10−9) did not change significantly over time; in contrast there was a threefold increase in the number of receptors per milligram tissue in day 7 wound tissue versus normal skin harvested at day 0 (17.3 ± 2.6 × 1010 versus 4.7 ± 2.5 × 1010, respectively, p < 0.05). Binding inhibition experiments showed that 125I‐insulin‐like growth factor‐I binding was most specific to insulin‐like growth factor‐I with insulin‐like growth factor‐I > insulin‐like growth factor‐II > insulin. This increase in binding was due to upregulation of insulin‐like growth factor‐I receptors rather than increased levels of insulin‐like growth factor‐I binding protein as less than 20% of the threefold increase in binding at day 7 could be attributed to insulin‐like growth factor‐I binding protein in membrane‐free extracts. The presence of specific, high‐affinity insulin‐like growth factor‐I receptors in the skin and their upregulation at day 7 after wounding suggest that insulin‐like growth factor‐I plays an important role during wound healing.
Acceleration of wound healing in aged rats by topical application of transforming growth factor‐β1
Authors: Puolakkainen Pauli A. , Reed May J. , Gombotz Wayne R. , Twardzik Daniel R. , Abrass Itamar B. , Helene Sage E.
Published: September 2002

The impaired wound healing associated with aging may reflect inadequate secretion or delivery of cytokines. Transforming growth factor‐β1 is a mitogenic polypeptide with beneficial effects on wound healing. In the present study we questioned whether topical administration of transforming growth factor‐β1 could improve the wound healing process in aged rats in vivo. Wound repair (from 1 to 14 days) was analyzed in full‐thickness incisional wounds from 2‐year‐old rats with or without a single topical application of transforming growth factor‐β1 (1 µg/wound) at the time of wounding. Identical wounds from 3‐month‐old, untreated rats served as controls. Histologic analysis showed a marked delay in several aspects of wound repair in the aged rats in comparison with that noted in the younger animals. Immunostaining of the wounds for proliferating cell nuclear antigen showed a reduction in the number of cycling fibroblasts in old rats. In addition, the number of capillaries per unit area of the wound as determined by a stain for Griffonin (Bandeiraea) simplicifolia lectin, and the number of inflammatory cells as identified by an antibody specific for macrophages, were also reduced in the wound area in old rats. Treatment with transforming growth factor‐β1 resulted in marked enhancement of the following parameters: cell proliferation, inflammatory cell and fibroblast influx, wound closure, and angiogenesis. As seen with in situ hybridization, a similar temporal pattern of expression of messenger RNAs corresponding to type I procollagen and Secreted Protein, Acidic and Rich in Cysteine (osteonectin), known to be prevalent in healing wounds, was observed in both young and aged rats. However, the levels of mRNA corresponding to these secreted proteins appeared to be reduced in wound tissue from aged rats. Treatment with transforming growth factor‐β1 subsequently resulted in an increase in the expression of both type I procollagen and Secreted Protein, Acidic and Rich in Cysteine mRNA in the wound tissue from aged rats. In summary, a single topical application of transforming growth factor‐β1 to the wounds of aged rats at the time of wounding was associated with a healing response that, in all the parameters of wound repair examined, was similar to that of young rats. Topical transforming growth factor‐β1 might therefore be beneficial in the treatment of dermal wounds in the aged.
Characteristics of growth, morphology, contractility, and protein expression of fibroblasts derived from keloid
Authors: Sato Hajime , Suzuki Akifumi , Funahashi Makoto , Takezawa Toshiaki , Ogawa Yutaka , Yoshizato Katsutoshi
Published: September 2002

Phenotypic alterations of keloid‐derived fibroblasts were characterized by comparison with the phenotypes of normal fibroblasts from the same patient. Explant cultures of keloids showed unique features. Keloid explants contracted considerably and reduced their size during culture, whereas the size of normal skin explants remained unchanged. Enlarged cells were found among fibroblasts which had grown out of all the explants and were morphologically distinct from fibroblasts; however, keloid explants produced many more of them than did the normal tissues. The growth rate of fibroblast colonies formed from normal explants was five times higher than keloid explants. Keloid fibroblasts which had been serially cultivated contracted lattices of collagen gels at a rate similar to normal fibroblasts. Proteins extracted from serially cultivated fibroblasts were mapped on polyacrylamide two‐dimensional electrophoretic gels. No significant qualitative alterations in protein expression in keloid cells were found as compared with normal fibroblasts. However, some quantitative changes were found between the two. A computer‐assisted image analyzer detected 151 polypeptide spots—50 spots (33%) of which increased their amounts in keloid cells, whereas 34 spots (22.5%) decreased in comparison with normal fibroblasts. Sixteen major polypeptides were identified as known proteins with the aid of time‐of‐flight mass spectrometry. The level of expression of these identified proteins was similar between normal and keloid cells, except stathmin whose expression was suppressed in keloid fibroblasts.
Expression of proliferating cell nuclear antigen in cultured middle ear epithelial cells of the guinea pig
Authors: Takeno Sachio , Hamamura Nobuhiro , Hirakawa Katsuhiro , Yajin Koji
Published: September 2002

Primary cultures of middle ear epithelium from the guinea pig were successfully established on type I collagen coated dishes. To characterize cellular outgrowth, antibodies to the proliferating cell nuclear antigen were used as a marker for spreading cells in the S phase of the cell cycle. A number of migrating epithelial cells positively stained for proliferating cell nuclear antigen after 7 and 14 days in culture. Confocal laser scanning microscopy was used to evaluate the localization pattern of this antigen, and the fluorescence intensity was quantified in different areas of the migrating epithelial sheet after various times in culture. Two distinct areas proved to be major sites of proliferating cell nuclear antigen expression. One was at the edge of the tissue explants from which multilayered epithelial cells had begun to migrate. The other was along the margin of the outgrowth, where the cells often had elongated shapes and were aligned in rows. The cells in both areas were identified as nonciliated cells; ciliated cells in the outgrowth showed little staining. We hypothesized that the outgrowth cells in this experiment might be identical to the migrating cells usually observed in renewing epithelia after injury. This model may provide a simple and reproducible method of evaluating the regenerative ability of the middle ear epithelium.
Canine subglottic stenosis as a model for excessive fibrosis: a pilot histologic and immunohistochemical analysis
Authors: Charous Steven J. , Ossoff Robert H. , Reinisch Lou , Davidson Jeffrey M.
Published: September 2002

We propose that the canine subglottic stenosis model can be used to investigate the pathophysiologic characteristics of excessive fibrosis. Submucosal and cartilaginous subglottic laser injuries in 22 dogs were created to compare normal wound healing with canine subglottic stenosis formation, human subglottic stenosis, and human hypertrophic scars. Tissues were evaluated for the content of proliferating cell nuclear antigen, collagen, and elastic fibers. Compared with normal mucosal healing, subglottic stenosis formation showed intensified and prolonged inflammation, delayed epithelialization, more mitotic activity, and greater collagen deposition. The model has several useful features. Stenoses can be produced predictably in dogs, with each animal serving as its own control. Endoscopic harvesting of subglottic scar can be performed repeatedly because restenosis occurs. Also, canine subglottic stenosis shares histologic characteristics with human subglottic stenosis and, perhaps, human hypertrophic scars. Future experimentation with this model should facilitate the understanding of excessive fibrosis.
Actin fiber orientation in connective tissue contraction: a quantitative study with the perforated rat mesentery model
Authors: Franzén Lennart E. , Reza Ghassemifar M. , Salerud Göran , Tarpila Erkki
Published: September 2002

Numerous fibroblasts with long cytoplasmic protrusions containing F‐actin appear during closure by contraction of rat mesenteric perforations. These protrusions are predominantly arranged parallel to the wound margin. In the present study, the spatial and temporal organization of such protrusions was quantitated during normal and retarded healing in zinc‐deficient animals. An orientation index, which gives the global orientation of the F‐actin fibers, was calculated after Fourier transformation of images generated in a laser confocal microscope. Actin‐rich fibroblasts began to accumulate at the wound margin on the first postoperative day, and the amount of actin gradually increased with time. The orientation index of the F‐actin in unperforated mesenteric membranes was low, whereas the orientation index around perforations increased significantly (p < 0.001) with time and reached a maximum level on postoperative days 5 to 7. The orientation index was significantly lower (p < 0.02) in membranes with retarded healing in zinc‐deficient animals than in controls. The findings show that image analysis can give valuable information about fibroblast organization during tissue repair and indicate that the spatial organization of the fibroblasts is an important factor in connective tissue contraction.
Accelerating effects of nonviable Staphylococcus aureus, its cell wall, and cell wall peptidoglycan
Authors: Levenson Stanley M. , Chang Tsueng H. , Kan‐Gruber Dorrine , Gruber Charles , Steinberg Jacob J. , Liu Xiaoguang , Watford Alvin , Freundlich Larry , Rojkind Marcos
Published: September 2002

We have previously reported that local application of viable Staphylococcus aureus dramatically accelerates wound healing, but viable Staphylococcus epidermidis does not. Because the S. aureus effect occurred in the absence of infection and because the cell walls of the two bacterial species differ, we hypothesized that nonviable S. aureus, its cell wall, and its cell wall component(s) would accelerate healing. Nonviable S. aureus was prepared by chemical and physical means, and its cell wall and peptidoglycan was prepared from heat‐killed cultures. In a large number of experiments, nonviable S. aureus (independent of the strain's protein A content), its cell wall, and peptidoglycan when instilled locally at the time of wounding each significantly increased the breaking strength of rat skin incisions (tested both in the fresh state and after formalin fixation). These agents also enhanced subcutaneous polyvinyl alcohol sponge reparative tissue collagen accumulation, generally by a factor of two. Histologic features of treated and control incisions were similar. In contrast, the reparative tissue of treated sponges contained more neutrophils, macrophages, capillaries, and collagen. These experimental data thus confirm our previous studies, as well as our hypothesis, and extend these observations of enhanced wound healing to specific fractions of the bacterial cell wall.
Hyaluronan: a potential carrier for growth factors for the healing of ligamentous tissues
Authors: Berry Shannon M. , Green Melvin H. , Amiel David
Published: September 2002

The anterior cruciate ligament has little capacity to heal after injury, in contrast to the medial collateral ligament. Cell migration and cell proliferation are essential steps in the wound healing of connective tissue, and we have developed an in vitro assay to study cell outgrowth (i.e., both cell migration and cell proliferation) from tissue explants. Using this assay, we have previously shown a synergistic effect of four growth factors on the early stages of cell outgrowth (i.e., at days 3 and 6) from these explants. Hyaluronan, a linear polysaccharide with a molecular weight of 3 × 106 daltons, has been shown to enhance the anterior cruciate ligament healing capacity in vivo by over 50%. The purpose of this study was to assess in vitro whether hyaluronan and the combination of growth factors (transforming growth factor‐β1 25 ng/ml, platelet‐derived growth factor‐BB 100 ng/ml, basic fibroblast growth factor 100 ng/ml, and insulin 25 µg/ml) would enhance cell outgrowth from explants at 3 and 6 days. At 3 days the mean cell outgrowth from the explants treated with hyaluronan and the combination of growth factors exceeded the growth in the explants treated with growth factors alone for the anterior cruciate ligament (mean cell count ± standard error: 19 ± 4 and 2 ± 1 cells, respectively) and for the medial collateral ligament (297 ± 40 and 87 ± 18 cells, respectively). At 6 days, the mean cell outgrowth in the presence of growth factors was enhanced sixfold by hyaluronan for the anterior cruciate ligament (160 ± 27 compared with 26 ± 15 cells) and fourfold for the medial collateral ligament (1363 ± 219 compared with 330 ± 74 cells). As previously shown, little cell outgrowth occurred from the anterior cruciate or medial collateral ligament explants when no growth factors were added to the modified Eagle's media at 3 and 6 days (<20 cells). For the medial collateral ligament only, hyaluronan had a small stimulatory effect on cell outgrowth in minimal essential media in the absence of growth factors. At 3 days the stimulation by hyaluronan was fourfold (31 ± 8 cells compared with 7 ± 4 cells), and at 6 days the stimulation by hyaluronan was nearly fourfold (73 ± 17 compared with 20 ± 12 cells). These results suggest that hyaluronan could be used together with growth factors in efforts to enhance the healing of ligamentous tissue injuries.
The Role of Magnetic Resonance Imaging in Late Presentation of Isolated Injuries of the Flexor Digitorum Profundus Tendon in the Finger
Authors: KUMAR B. A. , TOLAT A. R. , THREEPURANENI G. , JONES B.
Published: September 2002

Four patients had magnetic resonance imaging (MRI) after a clinical diagnosis of a flexor digitorum profundus tendon rupture of the hand. The delay before presentation ranged from 1 to 5 weeks. Three patients had closed ruptures and one had a minor laceration which had healed. MRI showed proximal retraction of the profundus tendon to the palm in two patients and limited retraction in the other two. MRI provides important preoperative information for surgical decision-making and planning in patients who present late with closed flexor tendon injuries of the hand.
Histological Appearances in Post-Partum de Quervain’s Disease
Authors: READ H. S. , HOOPER G. , DAVIE R.
Published: September 2002

Six patients who developed de Quervain’s disease during pregnancy or within 12 months of childbirth were treated surgically. Histopathological examination of the tendon sheaths using alcian blue stain showed that myxoid degeneration was responsible for the thickening observed in the sheath. Characteristic intramural deposits of mucopolysaccharides were present, predominantly in the sub-synovial region. Acute or chronic inflammatory changes were not seen. These findings were the same as those described in patients with de Quervain’s disease unrelated to pregnancy or childbirth.
Immediate De-Syndactylization of the Reverse Radial Forearm Flap
Authors: AL-QATTAN M. M. , ZIESMANN M.
Published: September 2002

The reverse radial forearm flap was used to cover soft tissue defects on the dorsal aspect of the hand and fingers with immediate de-syndactylization of the distal part of the flap in four cases. A total of 14 fingers were covered with de-syndactylized segments and these were divided into two groups. In group A (nine fingers) the defect extended to or just distal to the proximal interphalangeal (PIP) joint. The defect in group B (five fingers) was proximal to the PIP joint. Primary wound healing was observed in the proximal and lateral edges of the flap in all cases. However, delayed wound healing was observed in the distal edge of five of the 14 segments. All five segments that suffered from edge necrosis were from group A, indicating that longer segments are more likely to develop distal edge ischaemia. The fact that there was no major skin loss in any of the patients despite immediate de-syndactylization indicates that the reverse radial forearm flap has a reliable blood supply and can support a portion with a random blood supply without significant necrosis.
Carpal Tunnel Syndrome: Reconciling “Demand Management” with Clinical Need
Authors: BURKE F. D.
Published: September 2002

Purchasers of surgical services are seeking justification for operative interventions with increasing frequency. This paper seeks to identify all relevant data currently available for carpal tunnel decompression; one of the commonest operative interventions in hand surgery. Such data, as is available, would suggest carpal tunnel decompression rates in the United Kingdom are relatively low, with fairly prolonged preoperative duration of symptoms.
Feasibility of Partial A2 and A4 Pulley Excision: Residual Pulley Strength
Authors: MITSIONIS G. , FISCHER K. J. , BASTIDAS J. A. , GREWAL R. , PFAEFFLE H. J. , TOMAINO M. M.
Published: September 2002

We investigated residual digital flexor pulley strengths after 75% excision of the A2 and A4 pulleys. For direct pull-off tests, A2 and A4 pulleys from cadaveric fingers were tested by pulling on a loop of flexor digitorum profundus tendon through the pulley. For functional loading tests, fingers were positioned with the metacarpophalangeal joint flexed to 90° for A2 testing, and with the proximal interphalangeal joint in 90° flexion for A4 testing (with all other joints in full extension). Excision of 75% of A2 and A4 pulleys reduced pulley strengths determined by both testing methods. For the functional loading tests, which are more clinically relevant, mean tendon forces at failure after partial excision of A2 and A4 pulleys were 224 and 131 N respectively, which is sufficient to withstand flexor tendon forces expected during activities of daily living.
Histogenesis and Morphology of the Flexor Tendon Pulley System in the Human Embryonic Hand
Authors: SBERNARDORI M. C. , FENU G. , PIRINO A. , FABBRICIANI C. , MONTELLA A.
Published: September 2002

The number, position, structural and ultrastructural features of the flexor tendon pulley system in six human embryonic hands, aged from 6 to 12 weeks, were studied by light and electron microscope. The pulley system can be recognized from the ninth week; later, at 12 weeks, the structures are easily identified around the flexor tendon in positions closely correlated to those found during post-natal growth and in the adult hand. Structurally and ultrastructurally the pulleys are not simply thickened portions of the sheath. They are formed by three layers: an inner layer, one or two cells thick, probably representing a parietal synovial tendon sheath; a middle layer formed by collagen bundles and fibroblasts whose direction is mainly perpendicular to the underlying phalanx; and an outermost layer consisting of mesenchymal tissue with numerous vessels which extends dorsally in an identical layer, forming a ring that includes flexor and extensor tendons and the cartilaginous model of the phalanx. The pulley does not have a semicircular shape but a much more complicated one, owing to the middle layer which in part runs dorsally and in part ventrally, under the flexor tendons.
A Comparison of Dynamic Extension Splinting and Controlled Active Mobilization of Complete Divisions of Extensor Tendons in Zones 5 and 6
Authors: KHANDWALA A. R. , WEBB J. , HARRIS S. B. , FOSTER A. J. , ELLIOT D.
Published: September 2002

We present a prospective randomized trial of two groups of 50 patients each having complete zone 5 and 6 extensor tendon injuries. These were rehabilitated by the use of either a dynamic outrigger splint or a palmar blocking splint. The results were analysed using the Miller and TAM assessments. Good and excellent results were achieved in 95 and 98% of cases following dynamic outrigger mobilization and 93 and 95% of cases using palmar blocking splint mobilization, using the Miller and TAM assessments respectively. There was no statistical difference in the results obtained between the two groups. Therefore, we prefer the latter technique which is simple, cheap, more convenient and requires less therapy time.
Changes in Hand Function Following Wrist Arthrodesis in Cerebal Palsy
Authors: HARGREAVES D. G. , WARWICK D. J. , TONKIN M. A.
Published: September 2002

Eleven wrists in ten patients with cerebral palsy underwent wrist arthrodesis. All patients were reviewed between 6 and 121 months after surgery. Operative technique involved AO plate fixation in nine wrists. When the distal radial physis was still open (two wrists), stabilization was achieved using K-wires. A proximal row carpectomy was performed in eight patients. Soft tissue releases were necessary in three wrists. The procedure achieved its aim of improving hygiene and cosmesis. Functional improvement in the hand was noted in eight wrists. Function was consistently improved in athetoid patients.
Isolated Paralysis of the Extensor Pollicis Longus Muscle: A Further Variation of Posterior Interosseous Nerve Palsy
Authors: HORTON T. C.
Published: September 2002

A case of isolated extensor pollicis longus paralysis is reported representing a fourth, very localized, variation of posterior interosseous nerve palsy. Extensor indicis proprius transfer resulted in a return to function. As the posterior interosseous nerve supplies this and other muscles available for transfer, and the preoperative assessment of extensor indicis proprius function is difficult, the management of this localized nerve palsy presents a delimma to the surgeon.
Centro-Central Union for the Prevention of Neuroma Formation after Finger Amputation
Authors: BELCHER H. J. C. R. , PANDYA A. N.
Published: September 2002

Sixty digits undergoing terminalization were randomized to undergo either simple transection of the digital nerves (control) or direct suture of the nerves to each other (centro-central union, CCU). Thirty-one digits were available for review with a minimum follow-up of one year following the surgery. Assessment was by visual analogue scales (VAS) and clinical examination. Measurements included static two-point discrimination (S2PD) for sensation, dolorimetry for stump tenderness and grip-strength.

Resting pain, cold intolerance and perceived tenderness were comparable in the two groups. Perceived and observed touch sensitivity were better in the control group but the stumps in this group were more tender than those in the CCU group.

We conclude that CCU results in more comfortable stumps but causes greater loss of sensitivity. It is a simple and worthwhile adjunct to digital amputation.
Mycobacterium Kansasii Flexor Tenosynovitis Presenting as Carpal Tunnel Syndrome
Authors: WADA A. , NOMURA S. , IHARA F.
Published: September 2002

We present a case in which Mycobacterium kansasii flexor tenosynovitis caused the development of carpal tunnel syndrome. The diagnosis was made from synovial tissue specimens taken at the time of operation.
Arthroscopic Diagnosis and Treatment of Dorsal Wrist Ganglion
Authors: NISHIKAWA S. , TOH S. , MIURA H. , ARAI K. , IRIE T.
Published: September 2002

Thirty-seven patients with dorsal wrist ganglia underwent arthroscopic resection. The mean follow-up was 20 months, and no complications were encountered. The ganglia were classified into three types according to their arthroscopic appearance. This classification helps to determine the amount of dorsal capsular resection required.
Functional Outcome Following Salvage of Failed Trapeziometacarpal Joint Arthroplasty
Authors: RENFREE K. J. , DELL P. C.
Published: September 2002

The outcomes in 12 patients who underwent revision surgery for a failed trapeziometacarpal joint arthroplasty were assessed. Multiple procedures were common (an average of 4.5 per patient), and associated with an overall complication rate of 27%. However, after an average follow-up of 5 years, nine of the 12 patients reported improved function and ability to complete normal daily tasks. Most patients were satisfied with their level of pain relief, their grip and pinch strength, and their overall final result. The subjective outcome was less satisfactory in those involved in workers’ compensation litigation. All seven attempted scaphoid–thumb metacarpal fusions failed.
Avulsion Fracture of the Extensor Carpi Radialis Brevis Insertion
Authors: TSIRIDIS E. , KOHLS-GATZOULIS J. , SCHIZAS C.
Published: September 2002

Avulsion of the extensor carpi radialis brevis at wrist level is rare. We present a case of an avulsion fracture involving the extensor carpi radialis brevis insertion at the base of the middle finger metacarpal.
Flower Structure and Reproductive Biology of Bougainvillea stipitata (Nyctaginaceae)
Authors: López H. A. , Galetto L.
Published: September 2002

Abstract: Bougainvillea stipitata displays inflorescences with three pendant greenish flowers. Flowers open at sunset and last five days. Flower perianth is constricted in the middle and forms a tube that ends in five lobes. Fragrance is emitted by the papillae located on the lobe margins of the perianth. The nectary is located at the base of the staminal tube. It secretes fructose‐dominant nectar with amino acids, phenols and reduced acids. Nectar secretion is continuous during flower lifetime and the flowers do not recover the reward. Mainly moths visit flowers. Pollen load on stigmas indicates that most flowers received more than 50 pollen grains, which are deposited by pollinators within the first two days of the flower life. Although the low natural fruit set of this self‐incompatible species may be due to intraplant pollen flow, pollinators play an essential role for B. stipitata fruit production.
Formation mechanism of CdTe self-assembled quantum dots embedded into ZnTe barriers
Authors: Jang M. S. , Oh S. H. , Lee H. S. , Choi J. C. , Park H. L. , Kim T. W. , Choo D. C. , Lee D. U.
Published: September 2002

Photoluminescence spectra showed that the formation mechanism for CdTe layers grown on ZnTe thin films changed from a two-dimensional mode to a three-dimensional mode with increasing submonolayer CdTe layer thickness, and the temperature-dependent PL spectra indicated that the activation energy of CdTe quantum dots is larger than that of CdTe single quantum wells. The formation mechanism for the CdTe QDs is in reasonable agreement with a Stranski–Krastanov growth mode.
On the problem of algebraic completeness for the invariants of the Riemann tensor. III.
Authors: Carminati J. , Zakhary E.
Published: September 2002

We study the set CZ of invariants [Zakhary and Carminati, J. Math. Phys. 42, 1474 (2001)] for the class of space–times whose Ricci tensors possess a null eigenvector. We show that all cases are maximally backsolvable, in terms of sets of invariants from CZ, but that some cases are not completely backsolvable and these all possess an alignment between an eigenvector of the Ricci tensor with a repeated principal null vector of the Weyl tensor. We provide algebraically complete sets for each canonically different space–time and hence conclude with these results and those of a previous article [Carminati, Zakhary, and McLenaghan, J. Math. Phys. 43, 492 (2002)] that the CZ set is determining or maximal.
Twisted duality of the CAR-algebra
Authors: Baumgärtel Hellmut , Jurke Matthias , Lledó Fernando
Published: September 2002

We give a complete proof of the twisted duality property M(q)′=Z̃M(q⊥)Z̃* of the (self-dual) CAR-Algebra in any Fock representation. The proof is based on the natural Halmos decomposition of the (reference) Hilbert space when two suitable closed subspaces have been distinguished. We use modular theory and techniques developed by Kato concerning pairs of projections in some essential steps of the proof. As a byproduct of the proof we obtain an explicit and simple formula for the graph of the modular operator. This formula can be also applied to fermionic free nets, hence giving a formula of the modular operator for any double cone.
Chiral mixtures
Authors: Petitjean Michel
Published: September 2002

An index evaluating the amount of chirality of a mixture of colored random variables is defined. Properties are established. Extreme chiral mixtures are characterized and examples are given. Connections between chirality, Wasserstein distances, and least squares Procrustes methods are pointed out.
Spatial Holmboe instability
Authors: Ortiz Sabine , Chomaz Jean-Marc , Loiseleux Thomas
Published: September 2002

In mixing-layers between two parallel streams of different densities, shear and gravity effects interplay; buoyancy acts as a restoring force and the Kelvin–Helmholtz mode is known to be stabilized by the stratification. If the density interface is sharp enough, two new instability modes, known as Holmboe modes, appear, propagating in opposite directions. This mechanism has been studied in the temporal instability framework. The present paper analyzes the associated spatial instability problem. It considers, in the Boussinesq approximation, two immiscible inviscid fluids with a piecewise linear broken-line velocity profile. We show how the classical scenario for transition between absolute and convective instability should be modified due to the presence of propagating waves. In the convective region, the spatial theory is relevant and the slowest propagating wave is shown to be the most spatially amplified, as suggested by intuition. Predictions of spatial linear theory are compared with mixing-layer [C. G. Koop and F. K. Browand, J. Fluid Mech. 93, 135 (1979)] and exchange flow [G. Pawlak and L. Armi, J. Fluid Mech. 376, 1 (1999)] experiments. The physical mechanism for Holmboe mode destabilization is analyzed via an asymptotic expansion that predicts the absolute instability domain at large Richardson number.