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PubMed1976

Hyperacute renal allograft rejection in the primate. Therapeutic limitations of antiplatelet agents alone and combined with heparin.

Two antiplatelet drugs, pyridinolcarbamate and Sudoxicam, were tested separately and in combination with heparin for their ability to modify experimental hyperacute renal allograft rejection in primates. Pyridinolcarbamate delayed and amerliorated tissue injury and obstructive thrombosis but only minimally prolonged renal blood flow over that seen in untreated allografts, suggesting that graft failure was primarily due to vasoconstriction. Sudoxicam, an antiinflammatory agent, resulted in higher initial blood flow, but the duration of flow and graft survival were again only minimally prolonged. However, functional changes including C3, Factor II and X consumption were prevented, a net increase in Factor VIII activity was minimized, and fibrinolysis was inhibited. The combined effects of pyridinolcarbamate and heparin resembled those of heparin alone. Combination of Sudoxicam with heparin was more effective than heparin along in preventing intrarenal complement consumption, sequestration of formed elements, activation of coagulation, and inhibition of fibrinolysis. However, the latter combination also failed to prolong venous flow and graft survival over that seen with heparin alone.

Animals↗

PubMed2001

Human liver allograft acceptance and the "tolerance assay": in vitro anti-donor T cell assays show hyporeactivity to donor cells, but unlike DTH, fail to detect linked suppression.

Human allograft acceptance is associated with immune regulation, characterized by donor-antigen-linked suppression of delayed-type hypersensitivity (DTH). We wished to determine if "classical" in vitro assays of alloreactivity could also detect linked suppression and thus be useful in the clinical diagnosis of active immune regulation. We analyzed peripheral blood mononuclear cells from a group of eight liver transplant recipients, one of whom had stopped all immunosuppression 4.5 years ago yet continues to have good graft function (graft acceptor). The regulator phenotype was defined as the ability to suppress a DTH response to a recall antigen in the presence of donor antigen. Using the trans vivo DTH test, we identified four regulators, and four nonregulators. When we tested two of the regulators for in vitro mixed lymphocyte culture (MLC) and cytotoxic T lymphocyte (CTL) responses to B-lymphoblastoid cell lines (B-LCL), we found both patients to be specifically hyporesponsive to donor compared with third-party B-LCL stimulators. However, in contrast to the linked suppression of DTH seen when a given B-LCL expressed donor-type HLA-B antigens, there was no evidence of linked suppression in vitro, either in CTL, proliferative, or interferon-gamma cytokine release assays. The primary CTL hyporesponsiveness to donor B-LCL could not be reversed by neutralizing antibodies to transforming growth factor beta or interleukin-10, which could restore a strong DTH response to donor B-LCL. We conclude that DTH analysis can readily detect donor antigen-linked suppression in liver transplant recipients. CTL and MLC tests failed to do so. These findings may be relevant to the development of a tolerance assay suitable for use in clinical trials.

Antigens↗

PubMed2005

Rehabilitation of a bilateral maxillectomy patient with a free fibula osteocutaneous flap.

Rehabilitation of patients who have undergone bilateral maxillectomy is difficult because of extensive loss of bone and soft tissue. In this clinical report, prosthodontic rehabilitation of oral function in a bilateral maxillecitomy patient combined with a new fibular osteocutaneous flap, which was designed to have two oronasal slits for the retention of an obturator prosthesis, was described. A 58-year-old man with a maxillary alveolar carcinoma underwent bilateral maxillectomy. The defect was reconstructed using a vascularized fibular bone wrapped circumferentially with a peroneal flap, which was fixed with miniplates between the right malar prominence and cut edge of the left zygoma remaining two slits anterior and posterior to the graft. Two and half weeks after the surgery, a delayed surgical obturator was delivered and an obturator prosthesis was delivered 6 weeks after the surgery. This obturator prosthesis could be extended into the slits to engage the tissue undercuts, and was stable during use. Mastication, deglutition, articulation and the mid-facial profile of the patient were rehabilitated. After installation of the obturator prosthesis, relining of the prosthesis base was carried out alongside the healing process of the graft, and adjustment of occlusions and high-pressure spots was carried out. No clinical disorders were observed either in the grafted tissue or the obturator prosthesis with a 3-year prognosis. Newly designing a fibular osteocutaneous flap combined with tissue-borne obturator prosthesis is one successful approach to the restoration of oral function, and increases the patient's quality of life after bilateral maxillectomy.

Carcinoma, Squamous Cell↗

PubMed1987

[Effect of risk factors on early and long-term regional results following kidney transplantation].

An observational study by multifactorial statistical analysis was undertaken on 785 kidney transplants. Risk factors in first transplants for primary non-function are cold ischaemic time, donor centre and acute rejection, with a non-function rate of 8% and a delayed function of 37%. Risk factors for transplant survival are bad match, no preoperative transfusions, age of recipient below 40 years, male sex, diabetes, conventional immunosuppressive therapy and cadaver donors. Donor centre and delayed primary function have no influence on long-term kidney function. The analysis revealed additive effects of various risk factors. This has to be taken into account in recipient-selecting policy.

Cadaver↗

PubMed2005

Functional outcome of tibial plateau fractures treated with the fine-wire fixator.

OBJECTIVE: To review the functional outcome of patients with complex tibial plateau fractures treated with fine-wire fixation. DESIGN: Retrospective review with follow-up of patients in outpatient clinic. SETTING: Tertiary trauma center. PATIENTS: All patients who had fine-wire fixation for tibial plateau fractures between 1996 and January 2001 were reviewed. INTERVENTIONS: Fine-wire fixation with/without limited internal fixation for complex tibial plateau fractures. MAIN OUTCOME MEASURES: Knee range of motion, adequacy of articular surface reduction, mechanical axis, Knee Society Clinical Rating Scale and Short-Form 36 Health Questionnaire. RESULTS: Eighteen of twenty-one eligible patients were available for follow-up. There were 14 Shatzker VI and 4 V fractures. Seven fractures were open. Average follow-up was 28.2 months. All fractures united. There were three cases of delayed union, all progressed to union following additional procedures and bone grafting. There were no cases of osteomyelitis, septic arthritis or deep vein thrombosis. Seven patients had Knee Society Clinical Rating Scores of good/excellent (38.9%), and 11 had fair/poor scores (61.1%). Abnormal mechanical axes and multiple co-morbid injuries were associated with poorer outcomes. Although SF-36 scores were lower in the study group compared to matched population norms, 15 of 18 patients had full or partial return to pre-injury levels of functioning. CONCLUSION: Fine-wire fixation with limited internal fixation is a satisfactory method of managing complex high-energy fractures of the tibial plateau where soft tissue injury and bony comminution make traditional techniques of open reduction and internal fixation unsuitable.

Adult↗

PubMed1995

Treatment of closed tibial shaft fractures with unilateral external fixation.

Sixty-eight closed tibial shaft fractures were treated with an anterior unilateral external fixator over a 5 year period (1986-1991). Pin tract drainage and/or infection was seen in 71/380 pins. The total number of secondary operations, excluding planned pin extraction, during fracture healing was 61 (including 22 due to pin tract problems and 25 secondary corrections of alignment). Delayed union was seen in 14 fractures and non-union in three. Healing disturbances were more frequent following high-energy trauma. Bone grafting was done in 11 fractures. Eventually, all fractures healed within an average of 22 weeks. There were three refractures. At follow-up, on average 3 years after injury, functional results were excellent in 41 per cent, good in 46 and acceptable in 13 per cent. Due to the high number of unplanned secondary operations and prolonged healing times we do not consider the use of unilateral external fixation to be an adequate method for the treatment of closed tibial shaft fractures. The poor results are probably due to weight-bearing being too high in these patients relative to the mechanical stability provided by the external fixator system.

Adolescent↗

PubMed2026

Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.

Retinal organoids represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but the capacity of host cone bipolar cells in the primate macula to rewire with transplanted photoreceptors has not been established. In this study, we transplanted genome-edited ISL1-/- human retinal organoids lacking ON-bipolar cells into an acute laser-induced macular photoreceptor ablation non-human primate model. Using immunohistochemistry, ultrastructural imaging, and focal macular electroretinography, we demonstrate that host rod and cone bipolar cells actively extend dendrites toward grafted photoreceptors and form synaptic contacts, with evidence of functional signal transmission in a subset of transplanted eyes. Longitudinal, per-eye analyses revealed that host ON-bipolar responses improved in two of four eyes with ISL1-/- graft by up to 21.6% and remained stable for up to 2 years post transplantation. Moreover, OFF-pathway connectivity showed potential progressive maturation, with delayed increase in d-wave after 13 months in one of those eyes. These findings provide the first demonstration of long-term anatomical host-graft synaptic integration in the primate macula, establishing that central cone bipolar circuits retain the capacity for durable rewiring with human stem-cell-derived grafts. Our results highlight ISL1-/- retinal organoids as a promising approach for central vision restoration in macular degeneration.

Animals↗

PubMed2004

[Exotic snakes in Europe. A case of Mexican Moccasin (Agkistrodon bilineatus) snakebite].

INTRODUCTION: In the last years exotic snakebite envenomations are increasingly reported. These cases are difficult to manage because of the limited experience of European physicians in the treatment of bites from such venomous snakes; moreover, specific antivenoms are unevenly stocked and they are difficult to find in case of a medical emergency. OBSERVATION: A 39-year-old herpetologist was bitten in his right hand by a mexican moccasin (Agkistrodon bilineatus) at the workplace, and presented in the Emergency Department 19 hours later. At admission, clinical evaluation showed local necrosis, swelling involving the entire limb up to the trunk, and severe pain. The specific antidote, not stocked in Italy, was sought abroad; its finding and routeing up to spot delivery required 12 hours. The antivenom, given 32 hours after the bite with no adverse reactions, was only partially effective. The clinical course was characterized by extensive edema with rhabdomyolysis. The necrotic wound at the bite site required after several days surgical debridement, and eventually skin graft. At 3 months follow-up, motor impairment of his right hand fingers with functional disability was still present. COMMENTS: The envenomation by Agkistrodon bilineatus has some clinical aspects in common with that by European viper species, although crotalid venom usually causes more severe manifestations. The antivenom supply from a foreign country may delay its administration. A specific legislation aimed to simplify antidotes importing procedures for professional snake handlers may improve antivenoms availability and allow their timely use, as soon as clinically indicated.

Adult↗

PubMed1997

The omental flap with skin grafting for treatment of a difficult sternal closure.

A case report of difficult sternal closure is described. Chest closure following cardiac operation in critically ill patients can be a problem. Techniques have been described so that sternal closure can be delayed until the patient is hemodynamically stable and hemostasis has been achieved. However, in some instances, the sternal closure can not be performed because of prolonged cardiopulmonary instability. We describe the use of transposition of an omental flap with skin grafting in a 74-year-old patient with aortic valve stenosis, poor pulmonary function, and a thoracic deformity. This technique enabled incomplete sternal closure which maintained hemodynamic stability.

Aged↗

PubMed1996

Patterns of recovery among Norwegian heart surgery patients.

Utilizing a prospective longitudinal design, the recovery pattern of 91 heart patients was followed for the first 8 weeks following coronary artery by-pass graft surgery. The patients' perceived and actual performance of walking, their resumption of roles, and social support and family functioning were measured pre-operatively and at 4 and 8 weeks postoperatively. Findings indicate that recovery is swift in terms of health and physical functioning, somewhat more time-consuming in terms of role functioning, and delayed with regard to work-related role activities. Contrary to American findings, the heart surgery recovery process did not significantly affect family functioning in this Norwegian sample. Social support was experienced as high throughout the recovery period, with spouses and children being the main providers.

Activities of Daily Living↗

PubMed2005

The use of anterolateral thigh perforator flaps in chronic osteomyelitis of the lower extremity.

From April of 2000 to May of 2003, 28 consecutive patients with chronic osteomyelitis of the lower extremity underwent surgical debridement and reconstruction with anterolateral thigh perforator flaps (six cases were combined with vastus lateralis muscle flaps). All wounds were open for a minimum period of 6 weeks (average, 24.7 months; range, 6 weeks to 52 months). The average patient age was 42.8 years (range, 18 to 71 years), there were 21 male and seven female patients, and the average follow-up period was 18.2 months (range, 5 to 41 months). The cause of injury was an open fracture in 10 cases, secondary wound complications after reduction in eight cases, and diabetic foot in 10 cases. The surface defects ranged from 50 to 153 cm. The wounds were debrided an average of 2.5 times and then reconstructed with flap and treated with antibiotics for 6 weeks. Antibiotic beads were used in six cases and secondary bone graft procedures were performed in seven cases 3 months after the flap coverage. All 28 flaps were successful without any signs of recurrences or persistent osteomyelitis, but partial wound dehiscence was observed during early rehabilitation in two cases suspected of delayed healing caused by diabetes. These wounds healed spontaneously. All patients achieved acceptable gait function after rehabilitation. No debulking procedure was necessary in any case. Although the muscle flap is known to provide superior vascular supply, the type of flap used for coverage seems to be less critical in the final outcome, provided that total debridement and obliteration of dead spaces are achieved. A well-vascularized anterolateral thigh perforator flap was successfully used to combat infection and bring stability to wounds with chronic osteomyelitis.

Adolescent↗

PubMed1989

[Bone transplantation--indications and technic].

Autogenous spongiosa or, in osteoplastic surgery, autogenous corticospongious bones are considered as substance of choice for the surgical transposition of missing bones, to strengthen bones with insufficient loading capacity, and for a biological activation of atrophic bones. Even deep-freeze allogenous spongiosa can be inserted into a sterile, stable implantation site able to absorb the spongiosa to a large extent. The success will be delayed, but in the end a good functional result will be achieved with this method. In case of such an optimum implantation site, a comparable therapeutic effect can also be obtained with osteoinductive ceramics which can be modified with respect to their osteoinduction and loading capacity, both values showing a reciprocal ratio. Xenogenous bone grafts are no longer applied. A clinical example is presented in order to describe some criteria for the choice of a suitable transplant and to give some practical indications for its therapeutic application.

Adult↗

PubMed1996

Effects of complement inhibition with soluble complement receptor-1 on vascular injury and inflammation during renal allograft rejection in the rat.

Complement is both an effector of the humoral immune response and a stimulator of leukocyte activation. To examine the influence of complement on the allograft response, we inhibited complement using recombinant human soluble complement receptor-1 (sCR1; TP10), in an unsensitized model of rat renal allograft rejection. Lewis to DA renal transplant recipients were treated daily with 25 mg/kg sCR1 or saline and sacrificed on days 1 to 5 after transplant. Transplanted organs were examined histologically and immunohistochemically for leukocyte subset markers and for the third component of complement, C3, and membrane attack complex deposition. A second set of recipients was followed from day 5 to day 9 to assess graft survival. sCR1-treated recipients displayed > 90% inhibition of plasma complement activity and a marked reduction in tissue C3 and membrane attack complex deposition. Inactivation of complement reduced the vascular injury such that there was almost complete sparing of vascular damage in day 5 sCR1-treated rats. There was a significant reduction in infiltrating leukocytes by day 5 after transplant, and complement inhibition delayed the time to reach a histologically defined end point of graft survival from 5 days in controls to 9 days in the sCR1-treated group. These results imply that the vascular and cell-mediated injury arises, in part, from complement activation. The partial inhibition of these injuries by sCR1 may have functional implications for strategies to inhibit allograft rejection.

Acute Disease↗

PubMed1995

Prenatal alcohol exposure selectively suppresses cell-mediated but not humoral immune responsiveness.

The present study examined effects of fetal alcohol exposure (FAE) on the ability of peripubertal male and female rats to mount a humoral immune response against T-cell-dependent as well as independent antigens. The appropriate pair-fed (PF) and control (C) cohort rats were included. Serum immunoglobulins (Ig) levels were determined following a primary or secondary immune response. In addition, plasma corticosterone levels were measured in conscious, freely moving FAE, PF and C rats following sensitization with the T-cell-dependent antigen sheep red blood cells (SRBC). The study demonstrates that, in response to primary or secondary immunization, serum Ig levels in FAE rats were not significantly different from those in the PF or C cohorts. On the other hand, a marked reduction in mitogen-induced T-cell proliferative response was observed in FAE male rats in the same age group. Plasma corticosterone concentrations were increased almost four-fold 7 days after the primary immunization with SRBC, but there were no significant differences among the FAE, PF or C groups. Taken together, evidence from in vivo and in vitro studies indicates that FAE is associated with a selective impairment of cell-mediated immune function, including mitogen-induced T-cell proliferation, graft versus host as well as contact sensitization responses, but not of humoral immune function.

Animals↗

PubMed1989

[The significance of early dysfunction of the transplanted kidney].

The paper is concerned with the results of 39 transplantations of the kidney. All the patients received two basic immunosuppressants, namely prednisolone in a dose of 30 mg/day and Cy in a dose of 10-12 mg/kg a day. Within 6 to 11 months, the recipients' survival amounted to 82.5%, that of the organs to 84.5%. In 63.1% of the patients, immediate function of the transplant could be observed. It has been demonstrated that delayed function of the transplant was conjugated with reduction of the survival of the organs and recipients as well as with decrease of the quality of transplant functioning. Delayed function of the transplant might be determined not only by ischemic but also by immunologic injuries to the organ.

Adolescent↗

PubMed1993

Susceptibility and resistance to cyclosporin A-induced autoimmunity in rats.

Lethally irradiated Lewis (LEW) rats, reconstituted with syngeneic bone marrow and next given Cyclosporin A (CyA) for several weeks, develop disease (Cyclosporin A-induced autoimmunity; CyA-AI) after withdrawal of CyA. This disease resembles in terms of dermal changes the acute dermatitis and chronic scleroderma also seen in graft-versus-host disease (GVHD). In this study we report the relative resistance of the Brown Norway (BN) rat strain to the induction of CyA-AI. In contrast to LEW rats, in which CyA-AI was originally described, BN rats showed no acute dermatitis or scleroderma-like skin pathology in spite of comparable changes in the thymus and a maturation arrest of CD4+ T cells. The difference was also demonstrated functionally for whereas in LEW rats delayed-type hypersensitivity (DTH) reactions could not be elicited during CyA-AI, these were within normal limits in BN rats subjected to the same protocol; NK activity on the other hand was unaffected in both strains. The observation that BN rats developed very mild late disease as evidenced by a slight though significant weight loss suggests that the BN strain is susceptible to the disease but that lesser effector cell generation or, alternatively, stronger suppressor cell responses may prevent dermal disease. These observations may contribute to the elucidation of the mechanisms involved in this experimental autoimmune disease.

Animals↗

PubMed1985

The use of osteosynthesis in immediate and delayed mandibular reconstruction.

Principles of osteosynthesis utilizing dynamic compression plating have been used in immediate and delayed mandibular reconstruction in five patients. Intermaxillary fixation was not used. Follow-up ranged from eight to 14 months. Four of five patients have viable bone grafts at the present time. One bone graft has been lost due to infection. We feel mandibular reconstruction based on principles of osteosynthesis helps to rapidly restore cosmesis and function with minimal morbidity.

Bone Plates↗

PubMedDate not supplied

The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients.

BACKGROUND: Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS: We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS: Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS: Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.

Adult↗