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Serum protein immunogenicity: implications for liver xenografting.

The objectives of this study were threefold: (i) assess immunogenicity of donor plasma proteins following hepatic xenotransplantation, (ii) identify potential immunogens, and (iii) consider the implications of antibody formation against these plasma proteins in xenograft survival. We studied liver and heart xenografts in a concordant combination, hamster to rat. All grafts were examined at necropsy for evidence of rat immunoglobulin G (IgG) deposition. Cardiac xenografts were placed in recipients who had, or had not, been sensitized with hamster serum. Hepatic xenografts were placed in naive recipients to see if antibodies to hamster serum proteins could be eluted from the rejecting organ. Sera of immunized rats were examined for the presence of anti-hamster antibodies by immunoelectrophoresis and by Western blotting following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of hamster serum. Antibodies in sera of immunized rats were compared with those eluted from rejecting livers. Candidate antigens were identified by tandem mass spectrometry, sequence analysis, and reference to protein databases. Results showed that sera of immunized rats recognized a minimum of four different antigens in hamster serum by immunoelectrophoresis, and a minimum of seven by the more sensitive SDS-PAGE Western blot. IgG eluted from rejecting livers bound three of seven candidate antigens recognized by sera of the immunized animals. Sequence analysis searches revealed proteinase inhibitors in each of the three SDS-PAGE bands common to the above samples. All of these candidate proteinase inhibitor immunogens share a common catabolic fate, uptake via the lipoprotein-related protein (LRP/alpha 2-macroglobulin receptor (CD91). Sensitization to hamster serum proteins hastened cardiac xenograft rejection in 30-50% of recipients (depending on sensitization protocol). Vascular deposition of rat IgG occurred in all rejecting xenografts. Antibody binding to proteinase inhibitors could disturb their functional activity and contribute to the pathogenesis of delayed xenograft rejection.

Amino Acid Sequence↗

Gamma delta T cells are needed for ocular immune privilege and corneal graft survival.

It has been recognized for over a century that the anterior chamber of the eye is endowed with a remarkable immune privilege. One contributing component is the Ag-specific down-regulation of systemic delayed-type hypersensitivity (DTH) that is induced when Ags are introduced into the anterior chamber. This phenomenon, termed anterior chamber-associated immune deviation (ACAID), culminates in the generation of regulatory cells that inhibit the induction (afferent suppression) and expression (efferent suppression) of DTH. Since gamma delta T cells play a major role in other forms of immune regulation, we suspected they might contribute to the induction and expression of ACAID. Mice treated with anti-gamma delta Ab failed to develop ACAID following anterior chamber injection of either soluble Ag (OVA) or alloantigens (spleen cells). Additional experiments with knockout mice confirmed that mice lacking functional gamma delta T cells also fail to develop ACAID. Using a local adoptive transfer of DTH assay, we found that gamma delta T cells were required for the generation of regulatory T cells, but did not function as the efferent regulatory cells of ACAID. The importance of gamma delta T cells in corneal allograft survival was confirmed by blocking gamma delta T cells with GL3 Ab before corneal transplantation. While in vivo treatment with normal hamster serum had no effect on corneal graft survival, infusion of anti-gamma delta Ab resulted in a profound increase in corneal allograft rejection. Thus, gamma delta T cells are needed for sustaining at least one aspect of ocular immune privilege and for promoting corneal allograft survival.

Animals↗

Assessment of cosmetic and functional results of conservative versus surgical management of facial burns.

This study was undertaken to determine whether tangential excision and thick split-thickness skin grafting (STSG) of deep facial burns give a better cosmetic and functional result than conservative management. Forty patients (28 adults, 12 children) treated for facial burns between July 1989 and July 1991 were evaluated in follow-up (mean 18.3 +/- 8.3 months). The patients were categorized into the following groups according to depth and management of their facial burns: (A) healed without surgery in less than 21 days (n = 13), (B) healed without surgery in 21 days or more (n = 11), (C) early debridement and thick STSG in 18 days or less after the burn (n = 6), and (D) delayed debridement and thick STSG in more than 18 days after the burn (n = 10). Facial esthetics were evaluated by use of a modified scar assessment scale [range 0 (normal) to 16 (multiple abnormalities)], and functional problems of the face and neck were evaluated by use of physical examination. Group A patients had a significantly better overall rating on the scar assessment scale (2.1 +/- 2.9) than the patients in the other groups that required more than 21 days to heal, B (8.0 +/- 2.7), C (7.3 +/- 2.9), and D (5.7 +/- 2.5) (p < 0.01, analysis of variance). Also, skin-grafted areas in the surgically treated groups C and D had a significantly better scar rating than wounds that healed spontaneously in group B (5.7 +/- 4.0 vs 8.0 +/- 2.7, p < 0.05; and 5.1 +/- 2.6 vs 8.0 +/- 2.7, p < 0.05). There was no significant difference among groups B, C, and D when the total number of persistent functional problems after treatment were compared. The most common functional problems for these patients were microstomia (17/27) and eyelid ectropion (17/27). Patients with superficial facial burns that heal in less than 21 days appear to heal with generally very acceptable cosmetic and functional results. However, in those patients with deep facial burns that require prolonged periods for spontaneous wound healing, tangential excision of the wound and resurfacing with thick STSG appear to give better cosmetic results than conservative management, with no greater incidence of functional complications.

Adult↗

Function of a free jejunal "conduit" graft in the cervical esophagus.

The function of an autotransplanted jejunal graft used to reconstruct the pharyngoesophagus was evaluated in 12 patients, 2-40 mo after surgery. On clinical assessment most patients swallowed liquids and solids with minimal difficulty, although several described a need for liquids to "flush" solids to the stomach. Radiologic studies demonstrated a delay in orogastric transit in some patients above the lower anastomosis. The mechanism was apparent on motility studies: swallows generally failed to induce contractions in the graft, although the esophagus below exhibited stripping peristaltic waves. Regular contractile activity, characteristic of phase III of the intestinal migrating motor complex, was identified in 11 grafts. There was no temporal association between migrating motor complexes in the graft and those recorded at the jejunal donor site. Instillation of nutrients into the gastric antrum induced a typical "fed" pattern of contractions in the intact jejunum but not in the extrinsically denervated graft. In conclusion, the graft provides a useful, though generally passive conduit. The graft maintains its intrinsic motor repertoire, which is asynchronous with that of the donor site. The findings also support the hypothesis that extrinsic nerves are required to induce a "fed" pattern of intestinal motility.

Aged↗

FTY720 in combination with cyclosporine--an analysis of skin allograft survival and renal function.

Acute and chronic nephrotoxicity caused by CsA continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation. FTY720 is a new compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens. In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney. Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose could prevent graft rejection and avoid nephrotoxicity.

Animals↗

Value of stress thallium-201 emission tomography for predicting improvement after coronary bypass grafting and assessing graft patency.

To examine the value of stress and redistribution thallium-201 single photon emission computed tomography (SPECT) for predicting improvement after coronary artery bypass grafting (CABG) and for assessing graft patency, 17 patients underwent SPECT before and after CABG. Preoperatively, 16 patients (94%) showed reversible ischemia with redistribution, and defect score decreased from 16.4 +/- 7.6 to 8.3 +/- 5.8 (p less than 0.001) on 2 hour delayed images. Stress electrocardiography was positive in 15 cases (88%). The stress defect score was reduced postoperatively (7.8 +/- 6.3) as compared to the preoperative score (16.4 +/- 7.6) (p less than 0.001). Postoperatively, 7 cases (41%) showed reversible ischemia and the defect score decreased from 11.3 +/- 6.5 to 6.1 +/- 4.7 (p less than 0.05), while 4 cases (23.5%) showed positive stress electrocardiograms (ECG). Resting left ventricular (LV) ejection fraction (EF) improved in 6 cases (48.3 +/- 5.4% preoperatively to 56.8 +/- 7.4% postoperatively, p less than 0.05) and showed a reduction in 11 (58.2 +/- 10.5% to 47.5 +/- 9.4%, p less than 0.01). Grafts were occluded in 6 cases, and redistribution was evident on the delayed thallium images in all cases (100%), while stress ECG was positive in only 3 (50%). Thus, stress and redistribution SPECT is valuable for identifying patients who will improve after surgery and assessing graft patency more accurately than stress ECG. Resting LVEF was less useful for assessing improvement in LV function.

Adult↗

Monitoring the patient off immunosuppression. Conceptual framework for a proposed tolerance assay study in liver transplant recipients.

The mission of the recently established Immune Tolerance Network includes the development of protocols for the induction of transplant tolerance in organ allograft recipients and the development of assays that correlate with and may be predictive of the tolerant state. The state of clinical organ transplant tolerance seems to already exist in a small minority of conventionally immunosuppressed liver and, more rarely, kidney transplant patients. Immunosuppressive drug therapy has been withdrawn from these patients for a variety of reasons, including protocolized weaning for a uniquely large group of liver patients at the University of Pittsburgh. In this study, we propose to evaluate the validity of a variety of in vitro immunologic and molecular biologic tests that may correlate with, and be predictive of, the state of organ transplant tolerance in stable liver patients off immunosuppression. Only peripheral blood will be available for the execution of these tests. Both adult and pediatric liver graft recipients will be studied, in comparison to appropriate controls. We shall examine circulating dendritic cell (DC) subsets [precursor (p) DC1 and p DC2] including cells of donor origin, and assess both the frequency and function of donor-reactive T cells by ELISPOT and by trans-vivo delayed-type hypersensitivity analysis in a surrogate murine model. Cytokine gene polymorphism and alloantibody titers will also be investigated. It is anticipated that the results obtained may provide physicians with a tolerance assay "profile" that may determine those patients from whom immunosuppressive therapy may be safely withdrawn.

Abatacept↗

A critical role for CD48 antigen in regulating alloengraftment and lymphohematopoietic recovery after bone marrow transplantation.

The binding of CD2, present on T cells, to its counterreceptor CD48 facilitates adhesion, signaling, alloantigen-induced cytokine production, and cytotoxic T-lymphocyte responses. Because these T-cell functions have been implicated in graft-versus-host disease (GVHD) pathogenesis, we have analyzed the effects of the CD2:CD48 pathway on GVHD mediated by CD4(+) and CD8(+) T cells infused into sublethally irradiated recipients. CD4(+) T-cell-mediated, and to a lesser extent, CD8(+) T-cell-mediated GVHD was inhibited by CD2 + 48 monoclonal antibody (MoAb) infusion. To assess the effects of combined MoAb infusion on alloengraftment, two different alloengraftment bone marrow transplantation (BMT) models were used. In both, MoAb infusion markedly inhibited alloengraftment and hematopoietic recovery post-BMT. To determine if the adverse effects on lymphohematopoiesis in the allogeneic BMT recipients were caused by an immune or nonimmune mechanism, studies were performed in congenic BMT recipients to preclude an immune mechanism as the cause for delayed recovery post-BMT. MoAb infusion resulted in impaired lymphohematopoietic recovery in congenic BMT recipients and markedly reduced day 12 colony-forming unit-spleen formation in syngeneic BMT recipients, consistent with a nonimmune mediated mechanism. Because the spleen is a site of early hematopoietic recovery post-BMT, studies were performed using adult splenectomized syngeneic BMT recipients. MoAb infusion delayed recovery in both nonsplenectomized and splenectomized recipients post-BMT, indicating that the delayed hematopoietic recovery was not the consequence of an abnormal homing pattern of hematopoietic progenitors to the spleen early post-BMT. CD48 MoAb was necessary and sufficient for the inhibition of GVHD lethality and delayed lymphohematopoietic effects of the combined MoAb regimen. CD48 MoAb was found to induce a profound modulation of CD48 antigen expression on BM cells, suggesting that the CD48 antigen may have an important function in hematopoiesis in the BM compartment. Taken together, these data provide evidence that the CD48 antigen plays a critical role in regulating hematopoiesis in post-BMT.

Animals↗

Internal fixation vs. conventional therapy in midface fractures.

The purpose of this review is to evaluate internal fixation by means of AO miniplates compared to conventional therapy for the treatment of complicated midface fractures. A more precise division of midface fractures into functional units than that afforded by the Le Fort classification was employed to categorize the complexity of injury. The criteria of evaluation were ease of functional rehabilitation, incidence of complications, and results of surgery. The classification system was helpful in surgical planning and in subsequent analysis of results. Forty-nine of the 92 midface fractures treated by open repair between July 1980 and January 1986 were malar fractures, and 41 of these had associated orbital fractures. The remaining 43 had Le Fort II or more complicated midface fractures, only 15 of which could be adequately categorized by the Le Fort classification. Twenty-two of the 43 patients with complicated midface fractures were surgically treated with internal fixation utilizing 67 AO miniplates. The remaining 21 patients were treated with conventional therapy utilizing a combination of intermaxillary fixation (IMF), and/or interosseous wiring, and/or primary bone grafting. Among the problems encountered were a nonunion of the midface in a delayed repair of a severely comminuted midface fracture, which required secondary split rib grafting. Three plates were removed because of intraoral extrusion. There were no plate-related infections. One of the advantages of internal fixation is that the need for primary bone grafting and external fixation is eliminated. Another is that intermaxillary fixation is needed less frequently, allowing immediate access to the oral cavity for control of airway, care of intraoral wounds, and rapid return to normal alimentation with full mandibular function. Most patients with no associated GI problems tolerated a soft diet within 6 days. Tracheostomy tubes were removed within 3 days if no pulmonary failure was present. We can conclude that internal fixation provides excellent stabilization and repair of complicated midface injuries with minimal complications and rapid return to function for most patients.

Bone Plates↗

Late effects in children after bone marrow transplantation: a review.

Since the number of children receiving a bone marrow transplantation (BMT) and becoming long-term survivors continues to increase, more attention has to be paid to detect long-term side effects in these unique patients. Follow-up studies to timely identify these untoward sequelae are a matter of particular concern for pediatricians due to the longer life expectancy of children cured by BMT. The more frequently recognized sequelae affecting lung, eyes, brain and the endocrine system have been analyzed in this review. The majority of long-term side effects could be related to the conditioning regimens employed to prepare children before marrow transplantation and radiotherapy has been indicated as the most important agent determining deleterious toxicities. Most children receiving BMT present a decreased growth velocity and this growth impairment is especially observed in patients receiving total body irradiation (TBI) and prophylactic cranial irradiation prior to marrow transplant. Growth hormone deficiency could be demonstrated in the majority of patients with a reduced growth rate, even though an impairment of liver somatomedin production or a direct radiation-induced skeletal dysplasia could not be excluded. Overt and compensated hypothyroidism have been reported after TBI and patients given single dose radiotherapy are at greater risk with an overall incidence of thyroid function abnormalities approaching 30-40%. Delayed puberty development was reported in boys and girls after a TBI-containing conditioning regimen, whereas patients given BMT for severe aplastic anaemia presented a normal puberty. The absence of pubertal growth spurt contributes to the growth impairment of prepubertal children. In post-pubertal patients amenorrhea, azoospermia and gonadal failure can be observed after radiotherapy and several patients can require hormonal substitutive therapy. Skin and mucosal abnormalities referred to teguments involvement by chronic graft-versus-host disease (GVHD). Moreover, alopecia or abnormal pigmentation of the skin are observed in patients given busulfan as part of their myeloablative therapy. Cataracts are a well recognized complication of children receiving ionizing radiations and chronic steroid therapy. Again, posterior subcapsular cataracts occur more frequently in patients given TB1 as single exposure. Decreased lacrimal gland function, with impairment of tear production is another late effect of irradiation to the eye. Lung function abnormalities are not rare after transplant and may cause late mortality and morbidity.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Marrow Transplantation↗

Visible light induced changes in the immune response through an eye-brain mechanism (photoneuroimmunology).

The immune system is susceptible to a variety of stresses. Recent work in neuroimmunology has begun to define how mood alteration, stress, the seasons, and daily rhythms can have a profound effect on immune response through hormonal modifications. Central to these factors may be light through an eye-brain hormonal modulation. In adult primates, only visible light (400-700 nm) is received by the retina. This photic energy is then transduced and delivered to the visual cortex and by an alternative pathway to the suprachiasmatic nucleus (SCN). The SCN is a part of the hypothalamic region in the brain believed to direct circadian rhythm. Visible light exposure also modulates the pituitary and pineal gland which leads to neuroendocrine changes. Melatonin, norepinephrine and acetylcholine decrease with light activation, while cortisol, serotonin, gaba and dopamine levels increase. The synthesis of vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and neuropeptide Y (NPY) in rat SCN has been shown to be modified by light. These induced neuroendocrine changes can lead to alterations in mood and circadian rhythm. All of these neuroendocrine changes can lead to immune modulation. An alternative pathway for immune modulation by light is through the skin. Visible light (400-700 nm) can penetrate epidermal and dermal layers of the skin and may directly interact with circulating lymphocytes to modulate immune function. However, even in the presence of phototoxic agents such as eosin and rose bengal, visible light did not produce suppression of contact hypersensitivity with suppresser cells. In contrast to visible light, in vivo exposure to UV-B (280-320 nm) and UV-A (320-400 nm) radiation can only alter normal human immune function by a skin mediated response. Each UV subgroup (B, A) induces an immunosuppressive response but by differing mechanisms involving the regulation of differing interleukins and growth factors. Some effects observed in humans are: inhibition of allergic contact dermatitis; inhibition of delayed hypersensitivity to an injected antigen; prolongation of skin-graft survival and induction of a tumor-susceptible state. The following article will review much of the progress in this field and explore possible areas of future research.

Animals↗

Fractures of the radius and ulna.

Fractures of the radius and ulna are common in the dog and cat. If treated inappropriately, complications may result. These include delayed union, nonunion, malunion, and growth deformities. ESF is a versatile method of fixation for fractures of the radius and ulna. Types that are applicable range from the simple type I to the complex type III fixator. In general, the more unstable the fracture, the more rigid the assembly must be to counteract fracture forces. There are three basic phases to consider when using ESF: (1) preoperative planning, (2) application of the ESF, and (3) long-term management. A deficiency in any one of these phases can lead to complications and an unsatisfactory clinical outcome. Although ESF can be used on many types of fractures, the technique is especially well suited for open or highly comminuted fractures when internal fixation is not applicable. In these cases, close attention must be paid to the integrity of the soft tissues. In addition, cancellous bone grafts should be placed either at the time of initial repair or in a delayed fashion after adequate vascularity has been established. Staged or complete removal of the ESF should be individualized to each fracture case. In general, staged disassembly or "dynamization" can begin when the bone and fixator begin to function as a composite as determined by radiographs. Complete fixator removal should be considered when the fracture exhibits clinical and radiographic evidences of union.

Animals↗

Allograft rejection in C'6 defective rabbits.

27 skin allografts were transplanted in duplicate to 13 rabbits defective in the sixth component (C'6) of complement (C'). 14 were rejected within the normal period of time and 9 only after a significant delay. In four grafts, no rejection was observed. Grafts exchanged between C' active and C' defective littermates tended to persist viable longer on the C' defective partners. It is concluded that in a species of higher vertebrates, the rabbit, allograft rejection can proceed in the absence of C'6 and the biological functions depending on it. This includes the cytotoxic function of complement. However, the prolonged survival in C'6 defective rabbits of some allografts strongly suggests that two pathways may be operative in the rejection reaction. The results are consistent with the view that a mechanism independent of C'6 was alone fully effective in the majority of the donor-host combinations. A C'6-dependent mechanism became influential only in some specific donor-host combinations.

Animals↗

A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation.

Patient entry is now complete in a prospective trial of anti-Tac, a murine IgG2a monoclonal antibody directed against the p55 chain of the human IL-2 receptor, for the prevention of renal allograft rejection. Recipients of primary cadaver allografts were randomized to receive either anti-Tac (20 mg q.d. x 10 days beginning POD 1) plus low-dose CsA (4 mg/kg/day), azathioprine (2 mg/kg/day), and prednisone (30 mg q.d.), or conventional triple therapy with CsA (8 mg/kg/day), azathioprine, and prednisone. Forty patients were entered in each group, with current followup from 6 to 26 months. The results show a significant reduction in early rejection episodes in the anti-Tac-treated patients. During the 10-day treatment, 5 of 40 anti-Tac patients had rejection episodes, compared with 21 of 40 control patients (P less than 0.001). Anti-Tac significantly delayed the time to the first rejection (12.5 +/- 6.3 vs. 7.6 +/- 6.7 days) (P less than 0.05). Despite these effects, there were no differences in either actual or actuarial graft or patient survival between the two groups. Pneumonia, primarily CMV, developed in 5 treated and 4 control patients. In patients with functioning grafts mean serum creatinine at 3 months was 1.8 +/- 0.7 in the anti-Tac group and 2.0 +/- 0.8 in the control group (P = NS); at 12 months the values were 2.3 +/- 1.5 and 1.8 +/- 0.5, respectively (P = NS). The peak expression of IL-2 receptors on circulating T-cells was significantly lower in anti-Tac patients (15.1 +/- 3.6%) than in controls (21.9 +/- 4.5%) (P less than 0.05). Seven of 10 patients tested to date developed antimouse immunoglobulin antibodies, with antiidiotype shown in 6. These antibodies do not preclude subsequent treatment with OKT3. Five patients in this and previous anti-Tac protocols have received OKT3 for acute rejection despite known pretreatment antimouse antibodies, with resolution of rejection in all cases.

Adolescent↗

Lower limb soft tissue reconstruction using microsurgical techniques.

Trauma is the main cause of lower limb soft tissue defects followed by tumor resection, vascular disease and osteomyelitis. 17 patients were operated on using microsurgical techniques during the last 10 years. 9 of the patients had traumatic defects, 5 had various malignant tumors, 2 patients had arterial insufficiency and finally 1 patient had chronic osteomyelitis. The latissimus dorsi either as muscle flap with a split thickness skin graft or as a musculocutaneous flap was used the most frequently in our series. Other flaps, including the radial forearm neurovascular flap, the rectus abdominis flap, the scapular flap, the groin and the dorsalis pedis flaps were used less often. Delayed primary cover was used, except in 1 case with an opened knee joint trauma, where emergency repair was performed. Complications included: 2 partial skin graft necroses which required revision and 2 flap necroses caused by venous thrombosis. With follow-up more than 4 years in all but 2 patients, functional results were found satisfactory. Cosmetic results, however, were less satisfactory.

Adult↗

[Ligamentoplasty of the anterior cruciate ligament after 40 years: a series of 41 patients].

PURPOSE OF THE STUDY: Ligamentoplasty for tears of the anterior cruciate ligament (ACL) is generally thought to be unreliable after the age of 40 years. The purpose of this retrospective analysis was to assess the five-year outcome after ACL plasty in patients aged over 40 at the time of surgery. MATERIAL AND METHODS: Between 1990 and 1997, 41 patients aged 44.5 +/- 4.5 years (28 men, 25 right side) underwent intra-articular reconstruction of the ACL. Clinical and radiological assessment using the IKDC criteria was obtained at a mean 62 months postoperatively using manual instrumental measurements with KT-1000. The indication for reconstruction was instability in daily life activities for 40 patients and difficulties encountered in sports activities in one; there were three cases of remodeling. Arthroscopy was used in all cases to perform a patellar tendon graft (bone-tendon-bone in 30 cases associated with extra-articular lateral reinforcement in eleven). RESULTS: There were no significant complications. Among 12 patients who initially participated in competition sports, seven were able to resume their activity at their former level. At last follow-up, global IKDC score was A for 12, B for 25, and C for three and D for one. All patients scored C or D had a poor IKDC symptom score, basically because of pain. Motion was not modified. The IKDC radiology score was A for 25, B for 15 and C for one, but the three cases of remodeling did not progress. Prognostic factors for overall IKDC result were: age of the patient at the time of reconstruction (under 45 years), and the delay to surgery for accident victims (less than one year). The following criteria had no effect at last follow-up: gender, sport practiced, type of initial laxity (anterior alone or global anterior), presence of meniscal damage, preservation of the medial and/or lateral meniscus, chondral injury observed peroperatively, and use of a lateral reinforcement. Radiographic remodeling observed in this group of 41 patients was related to delay from accident to surgery (p=0.0007) and preservation of the medial meniscus (p=0.03). Age, gender, type of activity before surgery, degree of initial and residual laxity had no statistically significant effect on remodeling. CONCLUSION: Age over 40 years is not a contraindication for arthroscopic free patellar tendon graft for the treatment of chronic anterior laxity. Using rigorous preoperative assessment criteria (delay from accident to surgery, absence of joint space narrowing on the AP and lateral view before intervention, symptomatic instability in daily life activities and motivated patient) this type of procedure can be performed safely and provides good functional outcome at five years. The current follow-up is insufficient to judge potential joint degradation. Age is not a contraindication if certain precautions are taken.

Adult↗

Effect of altered lymphocyte function on immunologic disorders in NZB/NZW mice.

NZB/NZW F1 female mice were treated with the immunosuppresive enzyme L-asparaginar antibodies, diminished deposition of gamma-globulins in kidneys, significantly delayed the onset of proteinuria, and reduced deaths from nephritis. These effects were associated with reduction of cellular IgM antibody synthesis to both T-dependent and T-independent antigens, but the graft-versus-host reaction was not affected. After several weeks of therapy, antibodies against Asnase appeared in the circulation, the effect on antibody synthesis was lost, ANA and anti-DNA appeared, followed by proteinuria and deaths from nephritis. Therefore Asnase proved to be an effective therapy in NZB/NZW mice, but its usefulness was limited by the appearance of inactivating antibodies.

Animals↗

Delayed vaginal reconstruction in the fibrotic pelvis following radiation or previous reconstruction.

Vaginal reconstruction was performed in 14 patients who had developed vaginal stenosis secondary to extensive pelvic fibrosis after pelvic radiation therapy (12 patients) or prior vaginal reconstruction (2 patients). Sixteen procedures were performed using a split-thickness skin graft. All patients had satisfactory vaginal restoration, and 12 patients reported good vaginal function. No fistula developed as a result of the operative procedure, but one patient later developed a rectovaginal fistula resulting from tumor recurrence. Successful vaginal reconstruction can be achieved even years after initial therapy in patients who develop an obliterated vagina from previous radiation or surgery.

Adult↗