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PubMed1997

Syndactyly repair performed simultaneously with circumcision: use of foreskin as a skin-graft donor site.

A boy who had simple syndactyly involving the third web space of the left hand presented for elective syndactyly repair. Circumcision had been delayed because of neonatal medical problems. Elective syndactyly repair and circumcision were performed in one operation at age 9 months. Penile foreskin was used as a full-thickness skin graft for the syndactyly repair. The foreskin provided a functional syndactyly repair with good aesthetic characteristics. This obviated the need for two separate operations and for an additional skin graft donor site. To our knowledge, this is the first reported case in which foreskin was used for the repair of syndactyly. In boys with syndactyly, the authors advocate that parents be informed of this reconstructive option. Should the parents consider it to be suitable, then elective circumcision should be delayed until the time of syndactyly repair so that foreskin may be used for the syndactyly repair.

Circumcision, Male↗
PubMed1990

Generalized toxicity of L-leucyl-leucine-methyl ester for lymphocyte functions.

This study investigated the hypothesis that sensitivity to L-leucyl-leucine-methyl ester (Leu-leu-O-Me) can be used to identify a role for cytotoxic lymphocytes in alloreactivity. Treatment of donor lymphocytes with Leu-leu-O-Me profoundly inhibited their ability to induce three separate models of murine graft-versus-host reaction (GVHR). This was observed for all aspects of GVHR examined, including weight loss, splenomegaly and activation of natural killer (NK) cells. These effects were not influenced by whether specific cytotoxic T lymphocytes (CTL) were involved in individual models of GVHR. Leu-leu-O-Me not only eliminated NK and CTL activity in vitro, but had identical effects on the proliferation of T and B lymphocytes in response to a variety of mitogenic stimuli. Finally, Leu-leu-O-Me prevented immune lymphocytes from mediating both class I and class II major histocompatibility complex (MHC)-restricted delayed-type hypersensitivity (DTH) responses in vivo. It is concluded that Leu-leu-O-Me has non-specific toxicity for most lymphocyte function and that it cannot be used as a specific means of predicting the functional roles of CTL.

Animals↗
PubMed2003

Modulation of costimulation by CD28 and CD154 alters the kinetics and cellular characteristics of corneal allograft rejection.

PURPOSE: To examine the effect of modulating the lymphocyte costimulation pathways through CD28 and CD154 (CD40 ligand) in a model of corneal allograft rejection, with particular interest in changes in the observed features of rejection. METHODS: CD28 knock-out (CD28KO) and wild-type BALB/c control mice received corneal grafts from fully major histocompatibility complex (MHC)-mismatched C3H donors and were treated with CTLA4-Ig and/or anti-CD154 Ab on days 0, 2, and 4 after transplantation. Proliferation of BALB/c and CD28KO T cells in response to C3H stimulators was examined in a mixed lymphocyte reaction (MLR) in the presence of CTLA4-Ig or anti-CD154 Ab. RESULTS: Corneal allograft survival in wild-type BALB/c mice (median survival time [MST] 14 days) was significantly prolonged by blockade of the costimulatory pathways with CTLA4-Ig or anti-CD154 Ab (MST 21 days and 25 days respectively). MST in recipients treated with CTLA4-Ig and anti-CD154 Ab in combination was 29 days, not significantly longer than graft survival in single-treatment groups. MST in CD28KO recipients was 46 days and was not prolonged after treatment with anti-CD154 Ab (MST, 43 days). A similar result was found in the MLR, in which anti-CD154 Ab had no effect on proliferation of CD28KO compared with wild-type T cells. In CTLA4-Ig-treated CD28KO, grafts were rejected at an accelerated tempo, similar to that in wild-type BALB/c recipients (MST 16 days). More severe graft injury after the onset of rejection in untreated allograft recipients was accompanied by a higher number of graft-infiltrating CD45(+) cells, but similar proportions of CD4(+) and CD8(+) cells. CONCLUSIONS: CD28- and CD154-mediated costimulation have significant functional roles in corneal allograft rejection. Agents that modulate CD28 and CD154 pathways delay onset and reduce the severity of observed allograft rejection. However, their use in combination did not have an additive effect, MLR data indicating that the CD40-CD154 system depends on a functioning CD28 costimulatory pathway.

Abatacept↗
PubMed1998

[The results after 10-16 years of the treatment of chronic anterior laxity of the knee using reconstruction of the anterior cruciate ligament with a patellar tendon graft combined with an external extra-articular reconstruction].

PURPOSE OF THE STUDY: The aim of this prospective study was to evaluate the objective postoperative laxity and functional results with a minimum follow-up of 10 years (mean 11.7 +/- 2 years) in chronic anterior knee instability treated by ACL reconstruction associated to a lateral extra-articular plasty. MATERIAL AND METHODS: 138 patients of a mean age of 27.8 +/- 8.5 years had been operated. Delay between injury and operation was 4 +/- 4.8 years. The surgical "Mac Injones" procedure used a free autologous patellar tendon graft with a bone-to-bone fixation, supplemented by a lateral extra-articular plasty using a strip of quadriceps tendon as a direct prolongation of the graft of the patellar tendon and patella itself. A rehabilitation program aimed to an early recovery of a complete range of motion. Anterior laxity had been measured before and after operation using two instrumented methods, KT-1000 and stress-radiography (at 20 degrees of flexion with a 9 kg load applied at the distal part of the thigh) with measurements of the displacement in medial and lateral compartments. Tunnel positioning was appreciated radiologically. Function was evaluated using the International Knee Documentation Committee score (I.K.D.C.). RESULTS: Elongation of the reconstructed ligament occurred mainly during the first 6 month, but was independent from early full range of motion recovery. Laxity was stabilized after one year. The final laxity gain of the medial compartment was 62 per cent and for the lateral compartment 77 per cent. The pivot shift test was negative in 66 per cent, grade 2 in 4 per cent, grade 1 in 30 per cent. Functional results were excellent and good (A and B) in 60.4 per cent and 76.7 per cent returned to sports activity. 12 reconstructed ligaments reruptured. Arthritis was the cause of poor results in other cases (13.8 per cent). DISCUSSION: Lateral extra-articular plasty is unable to better control translation of the medial compartment than isolated anterior cruciate ligament reconstruction, but laxity of the lateral compartment was minimized and the pivot shift test also. Incorrect position of the anterior cruciate ligament was correlated with poor results. CONCLUSION: This documented study on laxity of the two compartments confirms the interest of each type of reconstruction, in particular extra-articular plasty when made with quadriceps tendon and so doing, preserving the iliotibial-band for the control of varus stability.

Adolescent↗
PubMed2000

Osteochondral autotransfer--newer treatment for chondral defects.

Osteoarthritis is believed to be accelerated by full thickness defects of articular cartilage. This article describes emerging therapies, including mosaicplasty autologous (i.e., the patient's own) graft and autologous chondrocyte implantation techniques. Patients with chondral defects caused by a variety of possible pathologies experience positive implications, including return to normal function and delaying the onset of osteoarthritis.

Chondrocytes↗
PubMed2000

Acellular nerve graft re-seeded by Schwann cells migrating from the nerve stump can stimulate spinal motoneurons for functional reinnervation of the rat muscle.

The acellular nerve graft was utilised to restore a functional reinnervation of the biceps brachii muscle from the motoneuron pool of the cervical spinal cord. The musculocutaneous nerve stump was sutured to an acellular nerve graft, the opposite end of which was inserted into the cervical spinal cord cranial to the avulsed C5 ventral root. The acellular nerve graft was repopulated by Schwann cells heavily immunostained for NGFr within 90 days. The Schwann cells migrating from the nerve stump reached the spinal cord grey matter, where they stimulated the motoneurons to send axonal sprouts. The functional reinnervation of the biceps brachii muscle was assessed by means of the behavioural (grooming) test and EMG, the presence of myelinated and unmyelinated axons was demonstrated by light and electron microscopy. The axonal reconnection of the musculocutaneous nerve stump was verified by horseradish peroxidase retrograde labelling of the spinal motoneurons. Moreover, the motoneurons on the operated side of the C5 spinal segment displayed increased immunostaining for GAP-43 in comparison to the contralateral side, whereas the pattern of AChE histochemical reaction was similar on both the operated and contralateral side, of the C5 segment 150 days after acellular graft implantation. The regenerated axons bridged a 4-cm long originally acellular nerve graft to reach and reinnervate the biceps brachii muscle. The reinnervation of the neuromuscular junctions was morphologically determined by immunofluorescence for neurofilaments. The number of myelinated axons in the acellular nerve graft was significantly higher than those growing over the cellular graft, but their diameter was smaller. The results of experiments presented here demonstrate functional recovery of the biceps muscle reinnervation through the acellular nerve graft repopulated by migrating Schwann cells. The process of reinnervation by acellular nerve graft is however delayed and worse in comparison with the cellular graft.

Animals↗
PubMed1978

Microsurgical composite tissue transplantation.

Since 1974, 69 patients with extensive defects have undergone reconstruction by microsurgical composite tissue transplantation. Using this method, donor composite tissue is isolated on its blood supply, removed to a distant recipient site, and the continuity of blood flow re-established by microvascular anastomoses. In this series, 56 patients (81%) were completely successful. There have been eight (12%) failures, primarily in the extremities. There have been five (7%) partial successes, (i.e., a microvascular flap in which a portion was lost requiring a secondary procedure such as a split thickness graft). In those patients with a severely injured lower extremity, the failure rate was the greatest. Most of these were arterial (six of seven). These failures occurred early in the series and were thought to be related to a severely damaged recipient vasculature. This problem has been circumvented by an autogenous interpositional vein graft, permitting more mobility of flap placement. In the upper extremity, all but one case were successful. Early motion was permitted, preventing joint capsular contractures and loss of function. Twenty-three cases in the head and neck region were successful (one partial success). This included two composite rib grafts to the mandible. Prolonged delays in reconstruction following extirpation of a malignancy were avoided. A rapid return to society following complete reconstruction was ensured. Nine patients presented for reconstruction of the breast and thorax following radical mastectomy. All were successfully reconstructed with this new technique except one patient. Its many advantages include immediate reconstruction without delayed procedures and no secondary deformity of the donor site. Healthy, well vascularized tissue can now be transferred to a previously irradiated area with no tissue loss. This new method offers many advantages to older methods of reconstruction. Length of hospital stay and immobilization are reduced. The total number of operative procedures required in achieving the desired result is also less, thus decreasing the cost of hospital care.

Arm↗
PubMed2005

VADER (vacuum-assisted dermal recruitment): a new method of wound closure.

Acute wounds which cannot be closed primarily are usually closed with a split skin graft. However a split skin graft has both functional (where tendons are exposed) and esthetic sequelae (contour deformity, different skin in color and texture). A novel technique is described which allows delayed primary closure of either fasciotomy wounds or full-thickness defects after harvest of a free or pedicle flap. The technique described combines the bootlace suture technique (which achieves wound closure by progressive suture tightening) with the VAC (vacuum-assisted closure) system (which reduces tissue edema, facilitating movement of tissue, and also reduces bacterial contamination of the wound). Twelve of 14 wounds (average width of wound after insertion and tightening of bootlace suture was 5 cm) were successfully closed after an average of 8 days (range, 4-23 days) in 11 patients (mean age, 45 years; range, 18-77 years) using this technique. Of the 2 patients where the technique was not successful, one patient was noncompliant and the other developed wound-edge necrosis. Other complications were self-limiting. The combined use of 2 methods of wound management facilitates delayed primary wound closure.

Adolescent↗
PubMed1975

Early recovery of albumin synthesis after liver transplantation.

The delay necessary for an orthotopic transplanted liver to recover in normal activity has never been defined. This is of great importance whenever liver transplantation is considered in patients with severe liver insufficiency. This delay was studied in dogs using albumin synthesis and BSP clearance as tests of liver function. Albumin synthesis was normal as early as 2 h following graft revascularization while BSP clearance was not yet normal by this time. It is suggested that transplanted livers will be rapidly able to corect metabolic disorders and above all coagulation problems in patients with terminal hepatic failure.

Albumins↗
PubMed1999

The heavy metal-responsive transcription factor-1 (MTF-1) is not required for neural differentiation.

The zinc finger transcription factor MTF-1 is essential for proper response to heavy metal load and other stress conditions in vertebrates, and also contributes to the maintenance of the cellular redox state. Target genes include metallothioneins (MT-I and MT-II) and gamma-glutamylcysteine synthetase (gamma-GCS), an enzyme involved in glutathione biosynthesis. Although MTF-1 is expressed ubiquitously, the primary defect in null mutant mice is hepatocyte necrosis, which results in embryonic lethality around day E14 and prevents the analysis of delayed effects on other organs. To assess the impact of MTF-1 deficiency on the function of the mature central nervous system, we employed the neural grafting strategy. Neuroectodermal brain tissue obtained from transgenic mouse embryos at gestational day 12.5 was transplanted into the caudoputamen of adult wild-type mice. 33 days later, grafts derived from MTF-1 deficient mice consisted of fully differentiated neuroectodermal tissue and showed no differences to heterozygous control grafts. This indicates that MTF-1 is dispensable for the development and differentiation of the nervous system. Such transplants devoid of MTF-1 may provide a useful tool for the further investigation of the effect of cell stress, including oxidative stress.

Animals↗
PubMedDate not supplied

The results of the surgical treatment of bone tumors using massive homoplastic grafts.

We reviewed our experience as concerns 588 patients treated by resection for bone tumor and reconstructed by massive bank bone implant. The period taken into consideration goes from 1984 to 2001. The mean age of the patients was 24 years with a minimum of 1 and a maximum of 77 years: in 186 cases (31.6%) age was lower by 14 years. Most of the patients were referred for a diagnosis of malignancy (85%), and of these, 70% had undergone antiblastic therapy postoperatively according to the modalities of the protocols. Of the cases that were not treated by chemotherapy there are 16 that had a homoplastic graft after failure of a previous one. In a high number of cases (189) surgery included reconstruction of an intercalar segment of a long bone. Of these, 106 were in the femur, 69 in the tibia, and 14 in the humerus. One joint reconstruction was carried out in 128 cases of which 52 in the knee, 49 in the shoulder, 10 in the elbow, 11 in the wrist, 3 in the ankle, and 3 in the metatarsals. Fusion, which was one of the most frequent indications in the eighties, is used less today; overall it was carried out in 91 cases of which 65 in the knee, 14 in the hip, 9 in the ankle and 3 in the wrist. This type of implant may also be used in the pelves, and this took place in 56 cases using different procedures of reconstruction. The most current method of reconstruction for a joint is composite prosthesis, and this was used in 124 cases of which 67 around a knee, 53 in the hip, 4 in the shoulder. Finally, in 78 cases a vascularized fibula transplant was associated with an intercalar graft, fusion, or osteoarticular graft to increase the mechanical capacity of the implant together with a more rapid integration of the implant, particularly at the osteotomic lines. Despite the excellent results demonstrated in the first 3 years of follow-up, infection, resorption, delay in consolidation and fracture led to 18% failures of the implant. Massive homoplastic graft is still a good means of reconstruction that allows for excellent functional results, but despite this intense research activity is required to improve its mechanical hold in time together with better and complete integration.

Adolescent↗
PubMed2003

APC0576: a novel small molecule, immunosuppressive agent effective in primate models.

BACKGROUND: APC0576, 5-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)-2-(4-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)phenoxy)pyridine is a novel synthetic compound with an inhibitory activity on NF-kappaB-dependent gene activation and chemokine synthesis in human endothelial cells. This article describes the effect of APC0576 on T-cell-dependent immune functions in vitro and in vivo in primate models, because NF-kappaB is known to be one of the potent mediators in T-cell activation. METHODS: The effects of APC0576 on interleukin-2 production and proliferative responses in human peripheral blood mononuclear cells were studied under various stimuli with in vitro culture assay. Next, female rhesus monkeys were immunized with tetanus toxoid (TTx), and APC0576 was orally administered for 4 weeks. Serum-specific antibody for TTx was monitored weekly using an enzyme-linked immunosorbent assay, and delayed-type hypersensitivity reaction was examined after 4 weeks of APC0576 treatment. To evaluate the immunosuppressive activity, APC0576 was orally administered for 32 days to rhesus monkeys that received transplants of allogeneic kidney. RESULTS: APC0576 effectively suppressed interleukin-2 production and proliferation in activated human peripheral blood mononuclear cells. Both delayed-type hypersensitivity reaction and specific antibody formation evoked by TTx was significantly and dose-dependently attenuated by 4 weeks treatment of APC0576 without any serious toxicologic signs. Allogeneic kidneys grafted in rhesus monkeys were not rejected and fully functioned during the 32 days of APC0576 treatment, although they were rapidly rejected after the withdrawal of the drug. CONCLUSIONS: A novel, orally available immunosuppressive agent, APC0576, effectively inhibited T-cell-based immune responses both in vitro and in vivo. APC0576 may have potential for a therapeutic agent in clinical organ transplantation and various cytokine-mediated diseases.

Animals↗
PubMed1998

[Proximal median and ulnar resections. Results of primary and secondary repairs].

PURPOSE OF THE STUDY: Recovery after median and ulnar nerve proximal repair is widely appreciated. The place and time for secondary functional reconstruction remains controversial. MATERIAL AND METHOD: From January 1983 to January 1990, 66 patients suffering from proximal injury of the median or ulnar nerves underwent nerve repair. Forty-five patients had a postoperative follow-up of more than 24 months: 24 isolated ulnar nerve lesions, 12 isolated median nerve lesions, and 9 combined median and ulnar nerve lesions. Ten patients were given a primary microsurgical nerve suture in our department. Thirty-eight patients underwent a delayed or secondary nerve repair of one or both nerves: 8 secondary nerve sutures, and 35 nerve grafts in 31 patients. RESULTS: Muscular strength, sensitivity, motion, and pain were better after primary nerve sutures (when technically possible) or after shortly delayed secondary sutures, although 40 per cent of patients treated with nerve grafts get final "good" or "very good" results. The time between the injury and nerve repair was the most significant prognosis factor. Results of ulnar nerve repairs at the elbow were statistically better with anterior transposition as compared to in situ repairs (p < 0.005). Fourteen patients required secondary functional reconstruction. Tendon transfers were performed at least 24 months after nerve repair. DISCUSSION: Nerve repair of proximal lesion to the median or ulnar nerves depends on the type of injury, but is advised even when delayed. Residual deficit following nerve repair should require functional transfers depending on hand sensitivity and extrinsic function.

Adolescent↗
PubMed2002

Locomotor performance of the rat after neonatal repairing of spinal cord injuries: quantitative assessment and electromyographic study.

In spinal cord injuries, various attempts have been made to reconstruct neural connections once disrupted. To improve current procedures and develop therapeutic methodologies it appears important to compare these reconstructive attempts via a standardized quantification of any ensuing functional recovery with parallel correlations to any potentially repaired neural connections. We have reported previously a quantitative assessment of neural connections across the graft site of rats whose spinal cord segments were neonatally replaced with embryonic spinal cord segments or a peripheral nerve section under comparable conditions. Using this same experimental model the present study assessed locomotor performance quantitatively using an open field locomotor scale at various postoperative intervals from day 0 to 5 weeks postinjury. To examine hind-forelimb coordination in further detail, electromyography was employed to record simultaneously from all four limbs during locomotion. Half of the rats whose spinal cord segments were repaired by replacement with embryonic homologous structures acquired virtually normal locomotor function, with a delay of five days compared with that of sham-operated rats. Detailed analysis revealed an abnormality in ankle joint movement and the stability of trunk during locomotion. Electromyography revealed that the pattern of locomotion in these rats was similar to controls. Grafted segments joined with the host spinal cord without gliosis at the host-graft interface. The remaining rats with an embryonic tissue graft showed various grades of hind-forelimb coordination. Gliosis and cavity were observed at the host-graft interface. The rats whose spinal cord was repaired by periphral nerve graft lacked hind-forelimb coordination despite the achievement of weight-supported steps. It appears likely that the grade of locomotor performance depends on quantity and quality of reestablished neural connections across the graft.

Animals↗
PubMed1992

Subdivision of flexor tendon "no man's land" and different treatment methods in each sub-zone. A preliminary report.

"No man's land" of the flexor tendon system is divided into 4 subdivisions based on our anatomical study. Clinically, a total of 72 flexor tendon injuries in "no man's land" were repaired during the primary and delayed primary stages. Different treatments of flexor tendons, sheath, vincula and postoperative exercises were used according to the degree of injury and anatomical and functional characteristics of each subdivision. The multiple intratendinous suture method, autogenous sheath graft and vincular repair were designed and attempted preliminarily in clinical practice. In 80.4% of the cases, excellent or good results were achieved. Comparison of treatment results in each sub-zone reveals that the IIc sub-zone is the most difficult area for satisfactory functional recovery in "no man's land". The significance of the subdivision of Bunnell's "no man's land" is discussed, and the preoperative assessment method of noting the extent of injury and selection of the treatment method for each sub-zone are presented in this paper. We believe that primary or delayed primary repair can restore good function to the repaired tendons. The effective way of enhancing treatment results of the tendon injury is to apply comprehensive treatment according to the extent of injury to the intrinsic healing capacity of the flexor digitorum profundus tendon.

Adolescent↗
PubMed1977

Delayed (degenerate) interfascicular nerve grafting: a new concept in peripheral nerve repair.

Interfascicular nerve grafts allowed to undergo endoneurial tube emptying in situ before transfer have been compared with grafts transferred fresh in terms of structure and function. The sciatic nerve of the rat was the model and its structure and ultrastructure were superior following degenerate grafting. More importantly, electrophysiological studies showed that function in nerves repaired with degenerate grafts was significantly better than in those repaired with fresh grafts.

Animals↗
PubMed1986

Segmental pancreatic autotransplantation with pancreatic ductal occlusion after near total or total pancreatic resection for chronic pancreatitis. Results at 5- to 54-month follow-up evaluation.

Reported are eight patients with idiopathic chronic pancreatitis and two patients with alcoholic pancreatitis who had near total distal pancreatectomy for disabling pain and underwent simultaneous segmental pancreatic autotransplantation of the body and tail of the gland to the femoral area in an attempt to prevent or delay the onset of diabetes. The median follow-up period was 31 months, and follow-up study in nine patients ranged from 24 to 54 months. Patency of the grafts was determined by angiography and selected percutaneous venous assays for insulin. Islet cell function was determined by oral glucose tolerance tests, intravenous (I.V.) glucose tolerance tests, and I.V. glucagon stimulation studies. Segmental autotransplantation was technically successful in eight patients, only one of whom required insulin (at 2 years after grafting). The other seven patients with technically successful grafts have remained insulin independent, including two patients who later underwent pyloric preserving pancreatoduodenectomy for completion pancreatectomy. Variable pain relief was observed in patients who underwent near total pancreatectomy, but pain was unrelieved in those patients who underwent limited distal resection. Patients with idiopathic pancreatitis appear to have better pain relief and preservation of endocrine function than alcoholic patients. Segmental pancreatic autotransplantation prevents or delays the onset of diabetes mellitus and should be considered as an alternative for those patients who require extensive pancreatic resection for chronic pancreatitis.

Adult↗
PubMed1988

Stabilization of fractures in the hand and wrist with traumatic soft tissue and bone loss.

Open type III fractures of the hand or wrist with severe bone and soft tissue loss justify aggressive treatment to restore anatomy, assure healing, and maximize functional recovery. The techniques of modern wound excision used at initial surgery predictably result in a decompressed and surgically clean wound within a few days from injury in the vast majority of cases. This allows a safe application of delayed primary internal fixation and bone grafting for fracture restoration or joint arthrodesis as well as early wound closure or coverage. The immediate or early application of stable external devices, internal fixation, or combinations of the two along with early bone grafting restores the structural integrity of the skeleton, reduces pain, protects other repaired and reconstructed tissues, promotes the healing, and supports early and intensive functional rehabilitation of the hand and wrist. Early wound closure or coverage minimizes scar formation. Together, the early sequencing of effective wound debridement with skeletal stabilization and bone grafting and early wound closure or coverage provide the most favorable circumstances for healing and functional recovery of the seriously damaged hand and wrist.

Adult↗