bluuebunny/crossref_metadata_2025 huggingface dataset:
A clinical comparison of unrelated cord blood transplantation and unrelated bone marrow transplantation for adult patients with acute leukaemia in complete remission
Authors: Ooi Jun , Iseki Tohru , Takahashi Satoshi , Tomonari Akira , Nagayama Hitomi , Ishii Koji , Ito Kiyoshi , Sato Hiroyuki , Takahashi Tsutomu , Shindo Motohiro , Sekine Rieko , Ohno Nobuhiro , Uchimaru Kaoru , Nagamura Fumitaka , Shirafuji Naoki , Tojo Arinobu , Tani Kenzaburo , Asano Shigetaka
Published: September 2002

Summary.  We performed a clinical comparison of unrelated cord blood transplantation (UCBT) and unrelated bone marrow transplantation in adult acute leukaemia patients in complete remission (CR) who received the same conditioning regimen, graft‐versus‐host disease (GvHD) prophylaxis and supportive treatment. The incidence of acute GvHD was almost the same between the two groups, but the haematopoietic recovery was delayed and the incidence of chronic GvHD was higher in the UCBT group. The probability of 2 year disease‐free survival was similar between the two groups. These results suggest that adult acute leukaemia patients in CR without a suitable donor should be considered as candidates for UCBT.
Alloantigen‐specific T‐cell depletion in a major histocompatibility complex fully mismatched murine model provides effective graft‐versus‐host disease prophylaxis in the presence of lymphoid engraftment
Authors: Koh Mickey B. C. , Prentice H. Grant , Corbo Marguerite , Morgan Melari , Cotter Finbarr E. , Lowdell Mark W.
Published: September 2002

Summary. Graft‐versus‐host disease (GvHD) is a multistep immune process involving lymphocyte activation, proliferation and target cell killing. We have devised a novel method for the selective depletion of alloreactive cells from haematopoietic stem cell grafts which retains a pool of immunocompetent lymphocytes possessing antiviral activity with the potential to hasten immune reconstitution. The method is based upon the expression of the activation antigen CD69 on responding donor lymphocytes in a cytokine‐modified mixed lymphocyte culture (mMLC) and depletion of these cells by paramagnetic bead sorting. We have previously demonstrated the in vitro efficacy of this system for the removal of alloreactive cells in both human leucocyte antigen‐mismatched and ‐matched settings. Here, we describe a non‐obese diabetic/severe combined immunodeficient murine model of aggressive GvHD in which we have tested its in vivo efficacy. Murine recipients of infusions of non‐manipulated major histocompatibility complex class I and class II mismatched donor T cells suffered rapid onset of acute, and generally fatal, GvHD. This model is akin to aggressive clinical transfusion‐related GvHD. Recipients of lymphocyte infusions depleted of CD69+ alloreactive donor cells ex vivo and monitored for 10 weeks post infusion demonstrated significantly improved survival (71·4% compared with 12·5% in the non‐manipulated group) and the absence of clinical GvHD despite the presence of circulating donor lymphocytes.
Validation of cytokeratin 5/6 as an effective substitute for keratin 903 in the differentiation of benign from malignant glands in prostate needle biopsies
Authors: Abrahams N A , Ormsby A H , Brainard J
Published: September 2002

Aims:  Keratin 903 (also known as anti‐cytokeratin antibody 34βE12) is widely used to differentiate benign glands from malignant glands in prostate needle biopsies. However, it is subject to considerable staining heterogeneity. We sought to evaluate the use of cytokeratin 5/6 (CK5/6) as an effective alternative to K903 in the evaluation of prostate needle biopsies in clinical practice.

Methods and results:  Thirty Hollandes‐fixed prostate needle biopsies were randomly selected over a period of 2 months from the surgical specimens accessioned over that period of time. Twelve cases had diagnosed prostatic adenocarcinoma (Gleason scores 3 + 3, 3 + 4 and 4 + 4) and the remaining cases (n = 18) were negative for carcinoma. Four sequential sections were stained with H&E (×2), K903, and CK5/6. Care was taken to preserve tissue so that matching glands were evaluated on all four sections. All cases were run routinely over a period of 3 weeks on a daily basis with matching positive controls. All slides were evaluated in a blinded fashion independently by two pathologists using a semiquantitative analysis of staining: <25%, 25–50%, 50–75%, >75% and >95% of benign glands (verified on H&E). Cases that showed no staining were repeated to ensure no false negatives. Both observers agreed with respect to percentage of staining in 96% of the cases. Twenty‐nine of 30 cases (97%) showed staining in >95% of benign glands with CK5/6. In contrast, K903 staining was seen in <50% of benign glands in five of 30 (17%), 50–75% in nine of 30 (30%), and >75% in 10 of 30 (33%), with only two cases (7%) showing >95% staining for K903. In four cases (13%) the K903 failed to stain any tissue even after repeat staining. K903 was conspicuously negative in atrophic glands in three of 30 cases (10%). Neither K903 nor CK5/6 stained malignant glands. Using a cut‐off of >75% staining in benign glands the sensitivity of CK5/6 and K903 was 97% and 40%, respectively.

Conclusions:  CK5/6 has superior sensitivity and reliability compared with that of K903 when evaluating routine prostate needle biopsies, including improved staining of atrophic prostatic glands. While K903 is traditionally used to differentiate benign glands from malignant glands, these results support the use of CK5/6 as an effective and reliable substitute for K903 in routine clinical practice.
Immunoglobulin Prolongs Survival of Pig Kidneys Perfused Ex Vivo with Human Blood
Authors: Fiane  , Videm  , Mellbye  , Foerster  , Geiran  , Gladhaug  , Svennevig  , Mollnes
Published: September 2002

Intravenous immunoglobulin (IVIG) (Octagam®), was used to determine the effect on hyperacute rejection in an ex vivo xenograft model. Six pig kidneys were perfused with IVIG and fresh human AB blood, and six control pig kidneys were simultaneously perfused with albumin and blood from the same donation. The survival of the IVIG‐perfused xenografts (median, 6.5 h) was significantly (P = 0.03) longer than the albumin‐perfused xenografts (median, 3.5 h). Complement was activated in both groups. The administration of IVIG to the perfused blood resulted in immediate and significantly higher complement activation in the fluid phase as compared with the albumin group. At rejection the fluid phase complement activation was higher in the IVIG group than in the albumin group for C1rs/C1inh complexes, C4bc, Bb and TCC. At the time of rejection both the albumin and the IVIG group demonstrated interstitial tubular haemorrhage, vasculitis or necrosis of glomerular capillaries and glomerular microthrombi. IgM, C1q, C3c, C4 and fibrin were located in arteries and glomeruli and IgG in the interstitium in both groups at rejection. The fluid phase findings are consistent with a modulatory effect of IVIG on complement activation by deviating the classical pathway activation towards the fluid phase. The prolonged survival of the IVIG‐perfused kidneys suggests that IVIG may be useful to dampen hyperacute rejection.
Antigen Receptor Cross‐Linking by Anti‐Immunoglobulin Antibodies Coupled to Cell Surface Membrane Induces Rapid Apoptosis of Normal Spleen B cells
Authors: Watanabe  , Nomura  , Takai  , Chiba  , Honjo  , Tsubata
Published: September 2002

Cross‐linking of surface immunoglobulin (sIg) has been shown to induce either activation or apoptosis of mature B cells presumably depending on the nature of antigens. However, the nature of antigens for induction of mature B‐cell apoptosis is not yet fully understood. We cross‐linked sIg of mature B cells with various amounts of either anti‐Ig antibodies in the soluble form or anti‐Ig coupled to erythrocytes or myeloma cells as surrogate membrane‐bound antigens. Anti‐Ig antibodies coupled to cell surface membrane induced rapid and extensive apoptosis of normal spleen B cells even in the absence of signalling via the Fc receptor. In contrast, soluble anti‐Ig induced proliferation or apoptosis of mature B cells depending on the concentration of anti‐Ig. The extent of apoptosis induced by soluble anti‐Ig was limited compared to that induced by membrane‐bound anti‐Ig. These results suggest that mature B cells undergo apoptosis or proliferation depending on whether antigens are soluble or membrane‐bound and on antigen doses.
Synergistic actions of platelet‐derived growth factor and the insulin‐like growth factors in vivo
Authors: Greenhalgh David G. , Hummel Robert P. , Albertson Steven , Breeden Matthew P.
Published: September 2002

Topical application of growth factors has been shown to benefit both normal and impaired wound healing. In normal tissue repair, resident cells produce a “cocktail” of various types of growth factors that overlap in function. In vitro studies have proved that growth factor combinations can act synergistically to enhance cellular function beyond that achieved with individual growth factors. To determine whether similar combinations have a synergistic effect in vivo, we applied growth factor combinations topically to full‐thickness skin wounds created in genetically diabetic mice. The C57BL/KsJ‐db/db mouse is obese and has insulin‐resistant diabetes, and it has been proved that this mouse has markedly impaired wound healing. Topical application of platelet‐derived growth factor, insulin‐like growth factor‐I, or insulin‐like growth factor‐II enhances healing in this model. Marked synergism was found when platelet‐derived growth factor and insulin‐like growth factor‐II were combined to produce augmentation in wound closure beyond that achieved by application of the individual growth factors. The synergistic effect allowed for improved tissue repair at doses of platelet‐derived growth factor and insulin‐like growth factor‐II that were ineffective when applied individually. The addition of insulin‐like growth factor‐I or insulin to platelet‐derived growth factor produced no significant synergism. Because multiple growth factors are released in the wound during the healing process, it is not surprising that their combination further enhances healing. Growth factor combinations should become an important addition to the armamentarium for the treatment of chronic, nonhealing wounds.
Regulatory concerns in the development of topical recombinant ophthalmic and cutaneous wound healing biologics
Authors: Stromberg Kurt , Chapekar Mrunal S. , Goldman Bette A. , Chambers Wiley A. , Cavagnaro Joy A.
Published: September 2002

The use of recombinant DNA technology has enabled the development of an increasing number of endogenous growth regulatory peptides for potential use as therapeutic biologics. Numerous such recombinant peptides are now licensed, and many are in various stages of pharmaceutical development. Although currently there are a number of “Points to Consider” and related guidance documents available concerning various issues of biotechnology‐derived products, the purpose of this article is to focus on the use of these biologics in topical ophthalmic and chronic cutaneous wound healing. Regulatory expectations with respect to product quality, safety, and efficacy that may be particularly germane to these products will be discussed. Providing regulatory guidance on these issues may not only facilitate the introduction of safe and effective new biologic therapies into clinical trials at the investigational level but also provide appropriate information to aid in their eventual approval for licensure and widespread clinical use.
Autocrine transforming growth factor‐β1 activity and glycosaminoglycan synthesis by human cutaneous scar fibroblasts
Authors: Messadi Diana V. , Berg Steve , Sung‐Cho Kyoo , Lesavoy Malcolm , Bertolami Charles N.
Published: September 2002

Transforming growth factor‐β1 is a well‐known and potent biological response modifier that plays an important role in tissue repair and fibrosis. Among the extracellular constituents known to accumulate in fibrotic tissues, glycosaminoglycans are prominent. In this study we examined transforming growth factor‐β1 synthesis by human dermal fibroblasts derived from both normal and fibrotic cutaneous tissues. We studied the influence of transforming growth factor‐β1 on glycosaminoglycan synthesis and explored the role of transforming growth factor‐β1 as an autocrine mediator of its own expression. These investigations are directed at understanding the persistence of the fibrotic phenotype in scarred skin. Transforming growth factor‐β1 activity was measured by means of a mink lung epithelium growth inhibitory assay. Replicate explants (n = 3) of fibroblasts each derived from normal skin, normal scar, or hypertrophic scar were studied by adding exogenous transforming growth factor‐β1 at a concentration range of 0 to 10 ng/ml. The resulting conditioned media were removed and assayed for transforming growth factor‐β1 activity, then the cells were pulsed for an additional 24 hours with radiolabeled glycosaminoglycan precursor, [3H]‐glucosamine, to evaluate glycosaminoglycan production. Cell‐free glycosaminoglycan synthetic profiles were also developed. Transforming growth factor‐β1 was found to cause a dose‐dependent increase in glycosaminoglycan synthesis in hypertrophic scar and normal skin but not in normal scar fibroblasts in cell‐mediated glycosaminoglycan synthesis; the reverse was observed in cell‐free glycosaminoglycan synthesis, where transforming growth factor‐β1 increased glycosaminoglycan synthesis in normal scar but not in normal skin or hypertrophic scar. Most endogenous transforming growth factor‐β1 existed in latent form for normal skin cells but in active form for normal scar and hypertrophic scar fibroblasts.
Interstitial fluids associated with wound repair support proliferation but not differentiation of neonatal rat myoblasts in vitro
Authors: Sicard Raymond E. , Nguyen Linh M. P.
Published: September 2002

The ability of wound fluids to support events required for skeletal muscle regeneration was examined. Wound fluids were obtained from polyvinyl alcohol sponges 1, 3, 5, 10, and 15 days after implantation. Neonatal rat L8 myoblasts were used to test the ability of early wound fluids to promote myoblast proliferation and late wound fluids to promote myoblast differentiation—two characteristics deemed critical for effective skeletal muscle regeneration. Early wound fluids (1‐ and 3‐day) stimulated DNA replication by myoblasts, as judged by tritiated thymidine uptake, up to ninefold (p < 0.05). Later wound fluids (5‐, 10‐, and 15‐day) displayed decreasing ability to stimulate proliferation, with 15‐day wound fluid failing to significantly stimulate proliferation. In contrast, myoblast differentiation, as judged by myotube fusion and creatine kinase activity, was progressively reduced by wound fluids of increasing age. In fact, late wound fluids (5, 10, and 15 days) reduced myotube fusion by 88% to 100% and depressed creatine kinase activity by 60% to 75% (p < 0.05). Thus, wound fluids from a repair environment appear to support myoblast proliferation early but suppress myoblast differentiation later. These characteristics suggest that the wound repair environment cannot fully support skeletal muscle regeneration.
Hyaluronic acid degradation products induce neovascularization and fibroplasia in fetal rabbit wounds
Authors: Mast Bruce A. , Frantz Frazier W. , Diegelmann Robert F. , Krummel Thomas M. , Cohen I. Kelman
Published: September 2002

Scarless fetal wound healing occurs with mild fibroplasia and neovascularization, while the wound is persistently enriched with hyaluronic acid. Conversely, adult wounds are characterized by prominent fibroplasia, neovascularization, and scar formation, and hyaluronic acid is a transient component of the early adult wound matrix. Our group has reported that enzymatic degradation of fetal rabbit wound hyaluronic acid results in marked increases in fibroplasia, collagen deposition, and neovascularization. This altered, adultlike healing response is hypothesized to have resulted from the generation of biologically active hyaluronic acid degradation products. Therefore, this study analyzes the fibrovascular inductive activity of hyaluronic acid degradation products. Fetal rabbit wounds were treated with hyaluronic acid degradation products generated by methods known to produce oligosaccharides with significant angiogenic activity. Implants from wounds treated with either of the control solutions (n = 4 for each control) had identical histologic features characterized by a mild mononuclear cell infiltrate but neither infiltrating fibroblasts nor collagen. In marked contrast, implants from wounds treated with hyaluronic acid degradation products contained infiltrating fibroblasts and collagen intermixed with numerous blood vessels. Quantitation of capillary ingrowth showed a sixfold increase in the neovascular response in wounds treated with hyaluronic acid degradation products compared with either controls (p < 0.05). This study shows that hyaluronic acid degradation products stimulate neovascularization and fibroplasia in fetal wounds. These observations suggest that a balance between hyaluronic acid accumulation and degradation has significant regulatory influence in fetal tissue repair.
Tissue restoration: approaches and prospects
Authors: Stocum David L.
Published: September 2002

This article summarizes the results of three basic research approaches directed toward achieving the restoration of injured or diseased human tissues. The three approaches are (1) to understand the differences in the molecular characteristics of cells and their environments in tissues which exhibit regenerative capacity at one stage of the life cycle but not at another; (2) to understand the molecular mechanisms whereby tissues regenerate by means of reserve progenitor cells or progenitor cells formed by dedifferentiation; and (3) to design artificial tissues for implantation into the body. These strategies should allow us to locate the key switchpoints which determine regeneration versus repair and how to reconfigure those switchpoints into a regenerative circuit where necessary or to build tissues in vitro that can serve as in vivo substitutes. For these strategies to be successful, we must understand the role of the immune system in repair and regeneration and the developmental roles of regulatory molecules, such as growth factors, trophic factors, extracellular matrix components, and the protein products of patterning genes, as well as the intracellular signaling systems activated by these molecules. The examples used to illustrate these themes are repair versus regeneration in wounded mammalian skin, the regeneration of injured mammalian bone and muscle by reserve progenitor cells, and the regeneration of the urodele limb, neural retina, and lens by progenitor cells produced by dedifferentiation. In addition, several approaches used in the construction of bioartificial tissues are discussed.
Prevention of postoperative adhesions with the chitin derivative N‐O‐carboxymethylchitosan
Authors: Krause Tyrone J. , Zazanis George A. , McKinnon Randall D.
Published: September 2002

The ideal barrier agent for the prevention of surgical adhesions has remained elusive. We have examined the ability of a new hydrogel N‐O‐carboxymethylchitosan, a derivative of chitin with properties similar to the extracellular matrix, to prevent adhesions when applied topically to traumatized mesothelial surfaces. In two rodent adhesion models (pericardial and peritoneal), the application of N‐O‐carboxymethylchitosan significantly prevented or minimized the formation of scar and fibrosis. According to a scoring system from 0 to 3 (0 = no adhesions and 3 = severe dense adhesions), control groups in each model consistently produced severe dense adhesions (2.9 ± 0.2, 2.7 ± 0.3). All treated groups consistently scored less than 1.0, indicating minimal or no fibrosis. The differences between the control and treated groups were statistically significant (p < 0.05). Thus, the application of N‐O‐carboxymethylchitosan to traumatized mesothelial surfaces may have significant potential in the prevention of postoperative adhesion formation.
Extracellular matrix protein turnover during salamander limb regeneration
Authors: Tassava Roy A. , Nace Jackie D. , Wei Yi
Published: September 2002

After amputation of a salamander limb, the extracellular matrix undergoes remodeling. The extracellular matrix that maintains the differentiated state of limb tissues is broken down and replaced by an extracellular matrix essential for dedifferentiation and blastema formation. We used monoclonal antibodies in immunohistochemistry methods and riboprobes in in situ hybridization to evaluate the upregulation of tenascin, type XII collagen, fibronectin, and the MT5 antigen. The Stump 1 antigen, an extracellular matrix protein that is abundant in the normal limb, is downregulated during regeneration and reappears late in regeneration as differentiation occurs. In the embryo, the Stump 1 antigen is also absent from the early limb bud and first appears during differentiation stages. Tenascin and fibronectin are also upregulated in the limb bud of the embryo, and these two extracellular matrix proteins appear to function during limb regeneration in adults and limb development in embryos. However, type XII collagen and the MT5 antigen are not found in the limb bud, indicating that type XII collagen and the MT5 antigen have roles in the regenerating limb but not in the embryo limb bud.
Differential effects of oxygen on human dermal fibroblasts: acute versus chronic hypoxia
Authors: Siddiqui Aamir , Galiano Robert D. , Connors David , Gruskin Elliott , Wu Liancun , Mustoe Thomas A.
Published: September 2002

The observation that many chronic wounds are ischemic has spurred a series of studies evaluating the response of cells exposed to hypoxia. To date, these studies have shown largely beneficial effects from hypoxia, such as increased cellular replication and procollagen synthesis. These findings are counter‐intuitive from a clinical standpoint because cellular growth and synthetic function are known to be retarded in chronic ischemic wounds. We have established an in vitro system in which human dermal fibroblasts grown chronically at 5 ± 3 mm Hg will proliferate at a rate three times slower than those fibroblasts grown under standard culture conditions (namely an oxygen partial pressure of 150 mm Hg). No phenotypic changes are noted in chronically hypoxic cells, and the growth‐retarding effects are reversible when the cells are returned to standard oxygen conditions. Competitive reverse transcription‐polymerase chain reaction showed that acute exposure to hypoxia (up to 1 week) results in a 6.3‐fold increase in the relative expression of transforming growth factor‐β1 messenger RNA, whereas chronic exposure to hypoxia leads to a 3.1‐fold decrease in this message. Collagen production measured at both the mRNA and protein level is also decreased in the setting of chronic hypoxia. We propose that this system may be the most appropriate setting for studying the role of oxygen on dermal fibroblasts in ischemic, nonhealing wounds.
Differential expression of platelet‐derived growth factor receptor‐β in an aging model of wound repair
Authors: Brucker Michael J. , Gruskin Elliot , Farrell Catherine L. , Siddiqui Aamir , Mustoe Thomas A.
Published: September 2002

Impaired wound healing as a result of age is a well‐documented phenomenon. However, the overall deficit in healing is substantially increased when the healing wound of an aged animal is ischemic. We hypothesized that both of these deficits are cytokine mediated. We have studied the messenger RNA expression of platelet‐derived growth factor receptor‐β, using the rabbit dermal ulcer model of wound repair, in young (3 to 6 months) and aged (48 months and 60 months) rabbits under normal and ischemic conditions. Platelet‐derived growth factor receptor‐β mRNA expression was measured with the use of quantitative reverse transcriptase‐polymerase chain reaction with incorporation of a synthetic, nonhomologous DNA fragment complementary to platelet‐derived growth factor receptor‐β primers as a competitive internal standard. Results in young rabbits showed a large upregulation of platelet‐derived growth factor receptor‐β mRNA expression after wounding. In both aged animal groups, platelet‐derived growth factor receptor‐β expression was found to be significantly decreased in nonischemic wounds relative to young nonischemic controls. Ischemia was found to have little effect on platelet‐derived growth factor receptor‐β mRNA expression in young animals relative to matched controls. However, ischemia induced a large decrease in the platelet‐derived growth factor receptor‐β mRNA levels of wounds of aged animals relative to paired aged nonischemic wounds. Results suggest an age‐related delay in platelet‐derived growth factor receptor‐β mRNA expression in healing wounds, as well as an age‐related decline in responsiveness to confounding ischemia.
Effects of cytokines in burn blister fluids on fibroblast proliferation and their inhibition with the use of neutralizing antibodies
Authors: Inoue Masayuki , Zhou Li‐Jun , Gunji Hironori , Ono Ichiro , Kaneko Fumio
Published: September 2002

Recent studies have shown that tissue exudates, such as burn blister fluid and donor site wound fluid, have promotive effects on wound healing. In the present study, results obtained with enzyme‐linked immunosorbent assays showed that at least three cytokines, transforming growth factor‐β1, transforming growth factor‐α, and interleukin‐6, exist at high concentrations in burn blister fluids. It was also found that these exudates were able to greatly enhance the rate of human fibroblast proliferation. However, neutralizing antibodies to transforming growth factor‐β1, transforming growth factor‐α, interleukin‐6, and platelet‐derived growth factor failed to prevent this proliferative effect. Ultrafiltration of the exudates showed these cytokines to be in the high molecular weight fractions (30 to 300 kDa and >300 kDa) and that these fractions retained mitogenic activity toward fibroblasts. Therefore it was postulated that the cytokines were bound to high molecular weight substances such as serum proteins in these exudates and could escape neutralization by antibodies directed against them.
Transforming growth factor‐β1 reduces expansion of open wounds in the fetal rabbit
Authors: Alaish Samuel M. , Olutoye Oluyinka O. , Yager Dorne R. , Liang Hui‐Xiu , Kelman Cohen I. , Diegelmann Robert F.
Published: September 2002

Open wounds in the fetal rabbit do not heal by contraction and actually expand between 60% and 90% over a period of 5 days. Experiments were carried out to determine whether transforming growth factor‐β1 can reduce expansion of open wounds in the fetal rabbit. This study was based on the concept that transforming growth factor‐β1 causes differentiation of fibroblasts into contractile fibroblasts or “myofibroblasts.” To test this hypothesis, pregnant New Zealand White rabbits underwent laparotomy and hysterotomy on day 24 of gestation. A circular full‐thickness cutaneous wound was made on the back of each fetus. After wounding, either vehicle alone or vehicle with transforming growth factor‐β1 was applied topically to the wound site, and each fetus was then returned to the uterus. The hysterotomy and laparotomy were closed in standard fashion. On postoperative day 5, fetuses were harvested by repeat Cesarean section. Wound areas were determined from photographs, calculated as percentage of original wound size, and expressed in square millimeters. In addition, a portion of each wound was fixed and processed for histologic and immunohistochemical analysis. At harvest, the control wounds had expanded by an average of 87% of the original area. In marked contrast, the transforming growth factor‐β1‐treated wounds had only expanded an average of 16%. Thus, transforming growth factor‐β1 significantly decreased the area of the open fetal wounds compared with control (p < 0.001). By histologic examination, no significant difference was found between the test group and the control group with regards to inflammation, neovascularization, collagen deposition, elastin content, glycosaminoglycan content, or hyaluronic acid content. Most notably, however, there was an increased density of fibroblasts in the transforming growth factor‐β1‐treated group. In addition, immunohistochemical staining with an anti‐α‐smooth muscle actin antibody showed the presence of contractile fibroblasts in the wound margins in the transforming growth factor‐β1‐treated group but failed to show any positive‐staining fibroblasts in the matrices of the control group. These results indicate that open wounds in the fetal rabbit treated in vivo with transforming growth factor‐β1 were significantly smaller than control wounds. This process appears to result from the recruitment and differentiation of normal dermal fibroblasts into contractile fibroblasts containing α‐smooth muscle actin.
The Use of Ultrasound in the Diagnosis of Injuries of the Ulnar Collateral Ligament of the Thumb
Authors: JONES M. H. , ENGLAND S. J. , MUWANGA C. L. , HILDRETH T.
Published: September 2002

We describe the use of a specialist referral clinic and ultrasound assessment for all injuries to the ulnar collateral ligament of the metacarpophalangeal joint of the thumb presenting to an Accident and Emergency (A&E) department. Senior House Officers in the A&E department were able to correctly diagnose only 45% of the ruptures of the ulnar collateral ligament. The overall agreement between specialist clinic examination and ultrasound for injury to the ulnar collateral ligament was 85% (kappa 0.647). When compared with the operative finding ultrasound had a positive predictive value for rupture of 94%. An algorithm is presented for the assessment of injuries to the ulnar collateral ligament in A&E departments.
Dynamic Radial Translation Instability of the Carpus
Authors: ALLIEU Y. , GARCIA-ELIAS M.
Published: September 2002

We report a case of a dynamic radial translation instability of the carpus, secondary to avulsion of the ulnocarpal ligaments and attenuation of the short radiolunate ligament. In addition, there was a peripheral detachment of the distal radioulnar ligaments causing distal radioulnar instability. Reattachment of the avulsed ligaments combined with a Sauvé-Kapandji procedure resulted in an excellent function, which was maintained 10 years after surgery.
Bipartite Scaphoid with Proximal Pole Osteonecrosis in a Patient with Holt-Oram Syndrome
Authors: TATE D. E. , GUPTA A. , KLEINERT H. E.
Published: September 2002

The Holt-Oram syndrome features a spectrum of upper limb abnormalities, including an abnormal shape of the scaphoid. Our report concerns a 19-year-old man with Holt-Oram syndrome and flattening and sclerosis of the proximal pole of a bipartite scaphoid. The initial ossification centre in the scaphoid was located distally at 8 years of age. By age 13, a pair of ossific centres were present. After an automobile accident at age 18, the proximal pole became sclerotic and then began to fragment over a 22-month period. Computed tomography confirmed the presence of two poles of the scaphoid and sclerosis and fragmentation of the proximal pole.
Arthroscopic Resection of Dorsal Wrist Ganglia and Treatment of Recurrences
Authors: LUCHETTI R. , BADIA A. , ALFARANO M. , ORBAY J. , INDRIAGO I. , MUSTAPHA B.
Published: September 2002

From 1995 to 1998, 30 patients with dorsal wrist ganglia and four with recurrent dorsal ganglia underwent arthroscopic resection. At a mean follow-up of 16 months, no complications were seen, but minimal pain persisted in three patients. Two recurrences were seen after arthroscopic resection of primary ganglia.
Nail Fold Creation in Complete Syndactyly using Buck-Gramcko Pulp Flaps
Authors: GOLASH A. , WATSON J. S.
Published: September 2002

We have used the double pulp flap technique described by Buck-Gramcko for nail fold creation in 75 fingertips after separation of 38 complete syndactyly webs in 27 patients. The operative technique is described and the results are discussed. Nail patterns in these complex syndactyly webs are analysed and a classification is proposed.
Long-Term Follow-Up of Surgical Correction of Madelung’s Deformity with Conservation of the Distal Radioulnar Joint in Teenagers
Authors: SALON A. , SERRA M. , POULIQUEN J. C.
Published: September 2002

Eleven wrists with painful Madelung deformity in seven patients were corrected during adolescence by a closing wedge osteotomy of the radius and a shortening osteotomy of the ulna, with conservation of the distal radioulnar joint. At late follow-up (9.7 years) function was considerably improved. When the ulnar head was correctly relocated during operation, a new distal radioulnar space developed. Shortening of the ulna must be generous and combined with slight flexion at the osteotomy.
A New Classification for Fingertip Injuries
Authors: EVANS D. M. , BERNADIS C.
Published: September 2002

A new classification of fingertip injuries is presented. The PNB classification separates the injury into its effect on the three components of the fingertip: pulp, nail and bone. This provides a three digit number that accurately describes the injury. This new classification can be used to record and document injuries, without having to resort to lengthy description. It could also be used to provide detailed instructions for treatment and indications for referral. Examples of the application of the classification are given.
The Extended Latissimus Dorsi Muscle Island Flap for Flexion or Extension of the Fingers
Authors: GOUSHEH J. , ARAB H. , GILBERT A.
Published: September 2002

We describe the technique of transferring the latissmus dorsi muscle as an island flap for the restoration of digital flexion or extension in 28 patients. The latissmus dorsi muscle is raised down to the posterior iliac crest and prolonged with the gluteal superficial facia. We believe that this method is particularly suitable for extensive and prolonged paralysis of the lower elements of brachial plexus. It can be used also for severe Volkmann’s contracture or the loss of flexor or extensor muscles of the fingers due to extensive debridement. The technique does not require microsurgery and there is no delay in reinnervation of the muscle.
Distraction Lengthening of the Forearm for Congenital and Developmental Problems
Authors: HORII E. , NAKAMURA R. , NAKAO E. , KATO H. , YAJIMA H.
Published: September 2002

Thirty-five callus distractions of the forearm were carried out in 23 patients, who were divided into two groups according to the cause of the shortening. Eleven cases in group A had congenital dysplasia, and the 12 cases in group B had growth disturbances from tumours or infection. The mean amount of lengthening was 27 mm in group A and 25 mm in group B. The mean percentage increase in length was 35% and 17%, respectively. The mean duration of fixation was 159 days and 127 days, respectively. The Healing Index had a positive correlation with the age at surgery in group A, but not in group B. The main complication was callus deformity after the removal of a fixator, which was especially frequent in group A. To avoid complications, the aetiology of shortening and the age of the patient should be considered when deciding the surgical protocol.
Primary Flexor Tendon Repair in Zone 1
Authors: MOIEMEN N. S. , ELLIOT D.
Published: September 2002

This paper presents an analysis of the results of repair of 102 complete flexor tendon disruptions in zone 1 which were rehabilitated by an early active mobilization technique during a 7 year period from 1992 to 1998. These injuries were subdivided into: distal tendon divisions requiring reinsertion; more proximal tendon divisions but still distal to the A4 pulley; tendon divisions under or just proximal to the A4 pulley; and closed avulsions of the flexor digitorum profundus tendon from the distal phalanx. Assessment by Strickland’s original criteria showed good and excellent results of 64%, 60%, 55% and 67% respectively in the four groups. However, examination of the results measuring the range of movement of the distal interphalangeal (DIP) joint alone provided a more realistic assessment of the affect of this injury on DIP joint function, with good and excellent results of only 50%, 46%, 50% and 22% respectively in the four groups.
An Accessory Extensor Tendon of the Thumb as a Cause of Dorsal Wrist Pain
Authors: BEATTY J. D. , REMEDIOS D. , McCULLOUGH C. J.
Published: September 2002

An accessory extensor pollicis longus muscle within the third extensor compartment resulted in dorsal wrist pain that resolved following excision of the accessory muscle.
Is the Reversed Fourth Dorsal Metacarpal Flap Reliable?
Authors: BENITO J. R. , FERRERES A. , RODRIGUEZ-BAEZA A. , MONNER J. , PALOMA V. , SERRA J. M. R.
Published: September 2002

We have carried out a study to determine if a flap based on vessels in the fourth metacarpal space could be used safely. We studied ten fresh cadaver specimens and used the flap in nine patients. In the anatomical study, we confirmed the presence of a suitable artery in nine out of the ten hands, arising from a piercing artery at the metacarpal bases, running distally under the fascia. The pivot point is located at the metacarpal heads, where the artery anastomoses to palmar branches and dorsal digital branches. In the clinical setting, the flap was reliable in eight patients. There was one case of flap necrosis. The flap seems to be reliable but several technical points are stressed to avoid complications.
Rupture of the Ulnar Collateral Ligament of the Metacarpophalangeal Joint of the Index Finger
Authors: AGUILÁ M. BOSCH , CARNÉ J. SOLANA , LLUCH A. HENRIQUEZ
Published: September 2002

We report a case of chronic instability due to rupture of the ulnar collateral ligament of the metacarpophalangeal joint of the index finger of the left hand. Because of persistent instability after the initial conservative treatment, surgical treatment was required.
Biomechanical Effectiveness of Taping the A2 Pulley in Rock Climbers
Authors: SCHWEIZER A.
Published: September 2002

Circular taping around the proximal phalanx is frequently used by rock climbers to treat tenosynovitis and to prevent injuries to the A2 pulley. The aim of this study was to determine the biomechanical effectiveness of such taping. Devices were built to measure physiological bowstringing in vivo, and to determine the force of bowstringing as well as the force applied to the pulley tape. Two kinds of taping on 16 fingers were measured during the typical crimp grip position. Taping over the A2 pulley decreased bowstringing by 2.8% and absorbed 11%of the force of bowstringing. Taping over the distal end of the proximal phalanx decreased bowstringing by 22% and absorbed 12% of the total force. Circular taping is minimally effective in relieving force on the A2 pulley. It is probably ineffective in preventing pulley ruptures.
Obstetric Brachial Plexus Palsy: A Large Animal Model for Traction Injury and its Repair
Authors: FULLARTON A. C. , LENIHAN D. V. , MYLES L. M. , GLASBY M. A.
Published: September 2002

A Sunderland type IV traction injury to the C6 root of the sheep or lamb brachial plexus was used as a model for obstetric traction injury to the C5 root in humans. The injury was created and immediately repaired using interfascicular nerve autografts in a group of adult sheep and a group of newborn lambs. The animals were examined using electrophysiological and morphometric techniques 1 year after operation. It was found that the recovery of neuromuscular function was superior in the lambs. The implication is that nerves in newborn animals have a better potential for regeneration than that seen in older individuals. This is discussed with reference to the management of obstetric brachial plexus palsy.
Scapholunate Ligament Repair Using the Mitek™ Bone Anchor
Authors: BICKERT B. , SAUERBIER M. , GERMANN G.
Published: September 2002

A retrospective study was done to assess the outcome after repair of completely ruptured scapholunate interosseous ligaments using the Mitek™ Mini G2 bone anchor. From 1994 to 1996. 12 patients underwent scapholunate ligament repair using the bone anchor. A follow-up assessment was done at a mean of 19 months postoperatively and revealed excellent or good results in eight patients, satisfactory in two, and poor in two patients, one of whom had developed lunate necrosis. One patient with an excellent functional result demonstrated recurrent dissociation of the scapholunate gap radiographically. The technique described proved to be simpler than conventional procedures in our hands, and yields similar functional results.
The Use of the Motion Analysis System for Evaluation of Loss of Movement in the Finger
Authors: CHIU H-Y. , LIN S-C. , SU F. C. , WANG S-T. , HSU H-Y.
Published: September 2002

We have used the motion analysis system to measure loss of finger movement after injury. The motion analysis system can provide information about the dynamic angular changes of each finger joint and the fingertip motion area for the injured finger. The latter can be used to calculate the percentage of fingertip motion area preserved. A stiff finger may show limited fingertip motion area with the finger joints tending to flex and extend together.
Static Splinting of Extensor Tendon Repairs
Authors: PURCELL T. , EADIE P. A. , MURUGAN S. , O’DONNELL M. , LAWLESS M.
Published: September 2002

In a prospective review we assessed the results of extensor tendon injuries managed postoperatively with a static splint. Thirty-three patients with 44 injured digits were assessed 4 months after primary tendon repair, using the Strickland-Glogovac criteria. Patients were managed in a static splint, the duration of which was guided by the zone of injury. Four months after repair, excellent or good results were obtained in 95%. Overall it was found that static splinting was an effective and safe method of management after extensor tendon repair.
Computer Model Analysis of the Swanson and Sutter Metacarpophalangeal Joint Implants
Authors: WILLIAMS N. W. , PENROSE J. M. T. , HOSE D. R.
Published: September 2002

A representative model which mimics the behaviour of Silastic® finger metacarpophalangeal joint implants was constructed using a finite element software package. The modelled implants were moved through a range of flexion, lateral deviation and a combination of both. Pistoning of both implants stems occurred within the modelled medullary cavities. For equivalent flexion angles, the Sutter implant produced a higher stress field than the Swanson implant, and the field was positioned at the central hinge mechanism. In both implants, lateral deviation increased the internal stress concentrations more than when pure flexion was applied. Overall the Swanson style of implant had lower stress magnitudes than the Sutter implant, and it is predicted that the Sutter implant will be more likely to fail than the Swanson. The failure mode for the Sutter implant would be at the central hinge region. The Swanson implant is likely to fail at the central hinge-stem interface regions.
Treatment of Chronic Injuries of the Ulnar Collateral Ligament of the Thumb Using a Free Tendon Graft and Bone Suture Anchors
Authors: MITSIONIS G. I. , VARITIMIDIS S. E. , SOTEREANOS G. G.
Published: September 2002

We report the results of a simple technique, using bone suture anchors and free tendon graft, for the reconstruction of chronic injuries of the ulnar collateral ligament complex at the thumb metacarpophalangeal (MP) joint. Our series includes 20 patients, with a mean age of 29 years. The mean follow-up period was 42 months. Using the Glickel grading system, 14 patients had excellent results and six had good results. Seventeen patients had no pain and three complained of mild pain with weather changes. Fourteen patients regained full stability of the MP joint and six had mild laxity. The mean loss of pinch strength was 18% compared with the contralateral thumb. The mean loss of motion at the metacarpophalangeal joint was 21%.
Hyaluronic Acid Modulates Cell Proliferation Unequally in Intrasynovial and Extrasynovial Rabbit Tendons In Vitro
Authors: WIIG M. , ABRAHAMSSON S.-O.
Published: September 2002

As tendons differ in biochemical composition and cellular capacities, we have compared dose response effects of hyaluronic acid on cell proliferation and synthesis of matrix components in intermediate and proximal segments of intrasynovial deep flexor tendons and extrasynovial peroneus rabbit tendons in vitro. Compared with matched control tendons, hyaluronic acid inhibited cell proliferation in intermediate and proximal intrasynovial flexor tendon segments at the concentrations of 0.1–2.0 mg/ml and 0.5–2.0 mg/ml respectively, but in extrasynovial tendon segments only at the concentration of 0.5 mg/ml. Hyaluronic acid did not affect synthesis of proteoglycan, collagen and non-collagen protein in either type of tendon. These results show that hyaluronic acid modulates cell proliferation unequally in intra- and extrasynovial tendons without affecting the synthesis of matrix components in the two types of tendons, indicating differential hyaluronic acid sensitivity and a possible mechanism of action.
Nerve Stripping: New Treatment for Neuromas of the Palmar Cutaneous Branch of the Median Nerve
Authors: LANZETTA M. , NOLLI R.
Published: September 2002

We present a new method for the treatment of painful neuromas of the palmar cutaneous branch of the median nerve. A preliminary cadaver study was done to investigate the extraneural and intraneural course of the palmar cutaneous branch of the median nerve with respect to the main trunk of the median nerve. Seven patients presented with a painful neuroma following previous surgery on the palmar aspect of the wrist. The neuroma was dissected and excised by stripping the whole of the palmar cutaneous branch from the main trunk of the median nerve. In all cases complete relief from pain and discomfort was achieved. The resulting area of numbness in the palm did not represent a significant problem.
“Uneasy Lies the Hand in which Rests the Crown” an Unusual Foreign Body Following a Punch Injury
Authors: MEHDI S. A. , DUNLOP D. G. , OLIVER C. W.
Published: September 2002

A case of cellulitis of the hand resulting from embedding of a dental crown following a punch injury is described. This report emphasises the need for X-ray imaging in all cases of penetrating hand trauma, particularly when the history is vague, and also the difficulty in using metronidazole in alcoholic patients.
Wrist Arthrodesis Following Ulnar Bar Excision in Fibrodysplasia Ossificans Progressiva
Authors: CORFIELD L. , HAMPTON R. , MCCULLOUGH C. J.
Published: September 2002

Fibrodysplasia ossificans progressiva is a rare disorder characterized by the progressive development of heterotopic bone in the connective tissues of skeletal muscle, ligaments and tendons. Surgical trauma is one of the most potent stimuli for ossification and surgical treatment is generally considered to be contraindicated in this condition. We report a good functional result in a patient with severe hand disability secondary to an ulna-carpal bar in fibrodysplasia ossificans progressiva.
Proximal Fractures of the Fifth Metacarpal: A Retrospective Analysis of 25 Operated Cases
Authors: PAPALOIZOS M. Y. , LE MOINE PH. , PRUES-LATOUR V. , BORISCH N. , DELLA SANTA D. R.
Published: September 2002

The clinical and radiological outcomes of 25 surgically treated fractures of the proximal third of the fifth metacarpal were retrospectively analysed. Many different methods of osteosynthesis were used. At follow-up after a mean of 3.3 years, 15 of 25 patients had no pain. Most patients regained a nearly full range of motion in the adjacent joints and more than 90% of the contralateral grip strength. X-ray signs of degenerative arthritis in the metacarpohamate joint were observed in 10 of 25 patients. Pain was found to be directly correlated with the presence of degenerative changes.