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PubMed2000

Longitudinal monitoring of immune reconstitution by CDR3 size spectratyping after T-cell-depleted allogeneic bone marrow transplant and the effect of donor lymphocyte infusions on T-cell repertoire.

Delayed immune reconstitution after allogeneic bone marrow transplantation (BMT) with associated infection is a major cause of morbidity and mortality. We used third complementarity region (CDR3) size spectratyping as a tool for monitoring T-cell repertoire reconstitution in 19 patients over a median time of 40 months after T-cell-depleted allogeneic BMT for chronic myeloid leukemia (CML). Furthermore, the effect of donor lymphocyte infusions (DLI) for the treatment of relapse in 18 of the 19 patients was analyzed. All BMT recipients had irregular spectratypes in the first 3- to -6 months after transplant. These evolved to more normal patterns by 12 months after transplant and continued to improve thereafter. In approximately a third of the patients, it took 2 to 3 years for all spectratypes to normalize, whereas in the other two thirds, some abnormal spectratypes persisted even after several years. In 9 patients, there was no immediate change in the CDR3 size profiles after DLI. In 3 patients, spectratypes improved slightly after DLI, whereas in 6 patients, spectratypes became more restricted and irregular. Overall, T-cell spectratypes in BMT patients were characterized by instability over time and in patients with graft-versus-host disease (GVHD), this was even more exaggerated. Several factors, such as pre-BMT conditioning, T-cell depletion of the donor marrow, loss of thymic function in adults, exposure to infectious agents, GVHD, and immunosuppressive treatment, are likely contributors to the delay in T-cell-repertoire reconstitution. (Blood. 2000;95:3990-3995)

Adolescent↗
PubMed1999

Impact of immunoadsorption on xenogeneic extracorporeal pig liver perfusion: assessment of organ function during autologous reperfusion.

The shortage of liver grafts has resulted in an intensive search for alternative strategies of liver support in acute liver failure. Extracorporeal perfusion of pig livers (ECLP) is not a new concept, but recent improvements in cardiopulmonary bypass technology and new knowledge about xenogeneic immunologic mechanisms have made it a potential therapeutic modality. In previous suboptimal experimental and clinical models, no statements about the beneficial effect of long-lasting periods of ECLP were made. The aim of this study was to evaluate the capacity of pig liver for metabolic regeneration after xenogeneic ECLP under largely physiologic conditions. To delay hyperacute rejection (HAR), we utilized immunoadsorption (IA) of naturally preformed xenogeneic antibodies (XNAbs). This led to a stable xenogeneic ECLP for 45 min. However, IA was not able to prevent completely organ damage or loss of function resulting from insufficient autologous reperfusion. The inability to regenerate during autologous reperfusion provides a new measure of the function of a xenogeneic perfused pig liver. In addition, our results implicate that patients with fulminant liver failure will benefit from short perfusions with several fresh organs rather than from long perfusion with a single pig liver.

Animals↗
PubMed1979

Transfer of specific unresponsiveness to organ allografts by thymocytes. Specific unresponsiveness by thymocyte transfer.

Prolonged survival of vascularized organ allografts has been produced in unmodified inbred rats by transfer of thymocytes from enhanced, engrafted, syngeneic animals. For these thymocytes to increase significantly the survival of test allografts they must be harvested 6-9 d after transplantation. Thymectomy of the enhanced, engrafted animals during the same critical period causes acute rejection of othewise long surviving grafts. For optimal effect, the enhanced thymocyte donor must be actively and passively immunized and receive a cardiac allograft. The necessity for erythrocytes in the initial active immunization regimen is noted. Additionally, the antigenic specificity of the suppressor effect has been established with two histoincompatible donor rat strains. Cellular and humoral host responses mounted by test graft recipients after thymocyte transfer from enhanced, engrafted donors are different from those mounted either by unmodifed animals acutely rejecting their grafts or by enhanced rats bearing well-functioning grafts. Numbers of T lymphocytes are reduced in the grafted hearts and in the spleens of test graft recipients, a finding paralleled by the complete absence of specific direct lymphocyte-mediated cytotoxicity. In contrast, cytotoxic antibody production, although delayed, is increased in magnitude, peaking around the time of graft rejection. These studies provide evidence that different biological manipulations can modify separate pathways in the complex cellular and humoral responses towards organ allografts. They demonstrate that cellular immunity is critically involved in immunological enhancement of vascularized organ allografts, a phenomenon hitherto considered primarily humoral. It seems clear that cells with suppressor activity are present within the thymus during the early phases of immunological enhancement.

Animals↗
PubMedDate not supplied

Platelet interactions with Dacron vascular grafts. A model of acute thrombosis in baboons.

We have developed a model of acute Dacron graft thrombosis in baboons in order to assess platelet alterations secondary to arterial thrombus formation. In this model, thrombus formation was initiated by Dacron vascular grafts inserted as extension segments into chronic arteriovenous Silastic shunts. Following platelet labeling with 111In-oxine, platelet deposition was measured for 1 hour following blood contact under arterial flow conditions using a scintillation camera. Graft platelet activity rapidly increased 40- to 50-fold, plateauing by 1 hour. All grafts produced equivalent reductions in circulating platelet count and blood 111In-platelet radioactivity, demonstrating that the labeled cells were functionally equivalent to the total platelet population. After graft placement, the remaining platelets survived normally. Acute platelet deposition was equivalent on grafts placed 1, 24, 48, and 72 hours following injection of the labeled cells, indicating that a variable delay between platelet labeling and graft imaging was without detectable consequence. Platelet destruction by the graft produced a tenfold increase in plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) but did not modify either the alpha-granule (PF4, beta TG) or dense granule (ADP, ATP) contents of circulating platelets.

Animals↗
PubMed2003

Fresh amniotic membrane transplantation combined lamellar keratoplasty for patients with recurrent Mooren's ulcer.

PURPOSE: To investigate the possibility of amniotic membrane as an immunological insulating band to reduce the recurrent frequency of Mooren's ulcer. METHODS: Twelve cases(12 eyes) with recurrent Mooren's Ulcer were observed. Among them, 4 cases (4 eyes) were male and 8 cases(8 eyes) female, ranging in age between 26 and 51 years [mean(41 +/- 3) years]. Three eyes recurred once, 5 eyes twice, and 4 eyes three before. Eleven of 12 cases (11/12 eyes) with frequently recurrent Mooren's ulcer underwent lamellar keratoplasty combined amniotic membrane transplantation (AMT). One patient who had entire corneal ulceration accepted AMT alone. RESULTS: Follow-up time is 12 to 29 months, [mean (23 +/- 6) months]. Before AMT, the recurrent frequency of Mooren's Ulcer of all cases after corneal surgery was 1-7 months [mean (3 +/- 2) months]. Nine of 12 eyes with lamellar keratoplasty combined AMT did not recur within the observation period; 2 eyes recurred 11 months after the surgery. Three months postoperatively, neovascularization was observed, which made it nearly impossible to decipher between amniotic membrane and its nearby conjunctiva, only at the junction of the transplant can some trails be observed. One case with entire AMT alone showed graft resolution and neovascularization in 1 month. CONCLUSION: AMT combined with lamellar keratoplasty and lesion excision may delay recurrence of Mooren's Ulcer, reduce its recurrent frequency. Besides the effects of decreasing inflammation, it may have immunological insulating function as well. This conclusion should be proven by further clinical comparative study of much more samples.

Adult↗
PubMed1984

Small intestine transplantation in the rat--immunology and function.

Heterotopic, vascularized small intestine transplants were performed in inbred strains of rats to investigate the structural, functional, and immunologic consequences of intestinal transplantation with and without immunosuppression with cyclosporine (CyA). Lewis X Brown Norway F1 intestine was rejected by untreated Lewis recipients in 7 to 10 days. Structurally, rejected intestine was characterized by shortened crypts and villi lined by damaged attenuated epithelial cells. Functionally, rejection was associated with impaired epithelial active ion transport as indicated by decreased potential difference and with diminished epithelial barrier function as reflected by decreased transepithelial resistance. Administration of CyA for 7 days prevented clinical rejection and partially prevented the structural and functional defects. Lewis intestine transplanted into Lewis X Brown Norway F1 recipients caused fatal graft versus host disease (GVHD) in 9 to 17 days. Treatment with CyA for 7 days failed to prevent GVHD routinely, but prolonged administration delayed fatal GVHD until CyA was discontinued. Intestine from Lewis "B" rats made deficient of T cells by thymectomy, irradiation, and reconstitution with syngeneic T cell-depleted bone marrow failed to cause GVHD in Lewis recipients. Reconstitution of the "B" rats with T cells before transplantation restored the GVHD response. These results may be relevant in the consideration of clinical small intestinal transplantation.

Animals↗
PubMed1993

Effect of intracerebroventricular infusion of epidermal growth factor in rats hemitransected in the nigro-striatal pathway.

The most recent attempt at surgical treatment of Parkinson's disease is represented by implant of dopaminergic tissue in the striate nuclei. Growth factors have been associated to the neural implants in order to favor successful grafting and functional survival. Among diverse growth factors Epidermal Growth Factor (EGF) is active in vitro on axonal regeneration of dopaminergic cells of the substantia nigra. Our research group has recently assessed the effect of a 35-day delayed intracerebroventricular infusion of EGF on the survival and function of the dopaminergic neurons in rats made hemiparkinsonian by unilateral mechanical transection of rat nigrostriatal pathway. EGF infusion resulted in a two-fold increase in the number of surviving tyrosine hydroxylase (TH)-positive substantia nigra neurons and a significant increase in ipsilateral striatal TH-positive fiber staining compared to controls. In addition there was a persistent enhancement of behavioral recovery, as indicated by a reduction in amphetamine-induced rotations. In the present study EGF is tested at a lower dosage starting administration at the time of lesion. Effects have been assessed by the available functional and biochemical methods. Results confirm that neurotrophic effect of EGF on dopaminergic neurons in the nigro-striatal pathways follow early administration also at low dosage.

Amphetamine↗
PubMed1993

Renal gunshot wounds: methods of salvage and reconstruction.

Over the past 14 years, 2079 patients have been seen at our institution with renal trauma. Of these, 84 sustained gunshot wounds (81 unilateral, 3 bilateral; a total of 87 renal units). We evaluated this group to characterize the nature of their injuries and establish a methodology for renal salvage and reconstruction. Preoperative radiographic staging was performed with excretory urography (IVP) or computed tomographic (CT) scanning. The injuries were classified into five categories: 16 contusions (18.4%), 12 minor lacerations (13.8%), 44 major lacerations (50.5%), six vascular injuries (6.9%), and nine combination laceration and vascular injury (10.3%). Most patients had multiple organ injuries, with 79 requiring associated surgical procedures (94%). The mean injury Severity Score (ISS) was 26.7 (range, 4-59). Based on radiographic and clinical staging criteria, 69 renal injuries were surgically explored (79.3%), and 12 patients underwent nephrectomy (13.8%). Forty-six renal units were reconstructed (66.6%) by various methods, including renorrhaphy, omental pedical flaps, mesh or peritoneal patch grafts, partial nephrectomy, and vascular repair. Overall, 75 renal units were salvaged (86.2%). Early renal vascular control was achieved in all patients who underwent renal exploration. Follow-up functional studies were done in 24 (28.5%): none had delayed nephrectomy or postinjury hypertension. Overall, 79 patients survived (94%); however, mortality was not related to renal injury. These findings suggest that aggressive radiographic staging coupled with early vascular control and careful selection of reconstructive techniques can ensure a high renal salvage rate in patients with renal gunshot injuries.

Adult↗
PubMed1997

[Immunological effects of erythrocyte and leukocyte transfusion. Work Group Blood Group Serology of the Medical Advisory Commission of the College for Blood Transfusion of the Netherlands Red Cross].

Immunological consequences of blood transfusion are less well-known than infectious complications although they occur more frequently. In many cases the effects in individual patients are hardly visible although fatal transfusion reactions may occur: Transfusion of red cells may induce acute or delayed haemolytic transfusion reactions. Transfusion of leukocytes may suppress the function of the immune system of the recipient (with consequences for immune tolerance in transplant patients, cancer surveillance and the occurrence of postoperative infections) but also may induce graft versus host disease.

Erythrocyte Transfusion↗
PubMed2001

Delayed primary excision and grafting of full thickness alkali burns of the hand and forearm.

In a prospective study, 15 cases of domestic alkali drain cleaner burns involving the dorsal aspect of the hand and forearm were included. There were ten males and five females. The average age was 27 years and the mean total body surface area burnt was 2%. All patients failed to do immediate water lavage at home and hence all wounds ultimately required excision and grafting. Patients were initially treated with daily silver sulfadiazine dressing on an out-patient basis. Seven to 9 days after injury, patients were admitted to hospital and underwent excision and grafting. On final follow-up, there was excellent return of function, which was assessed using the grip strength of the hand and the range of motion of the wrist and fingers. Cosmetic appearance and texture of the graft were assessed according to a proposed grading system. The cosmetic result was considered satisfactory in 12 patients and poor in three patients. There were no excellent cosmetic results, because of hyperpigmentation of the healed graft. Advantages of delayed primary excision and grafting of full thickness alkali burns of the hand and forearm are discussed.

Adult↗
PubMed2004

Delayed chronic type A dissection with a functional midline crossing right internal thoracic artery after CABG: surgical approach to an ascending aorta without dissecting the midline crossing internal thoracic artery.

We successfully treated chronic type A dissection and coronary artery disease with a functional midline crossing right internal thoracic artery (RITA) after coronary artery bypass grafting (CABG). A 68-year-old man was incidentally diagnosed as chronic type A dissection by follow-up cardiac catheterization after CABG, with 90% stenosis in the right coronary artery (RCA) No. 2. The dissecting aneurysm (max. 6 cm in diameter) was localized at the right portion of the ascending aorta with a functional RITA to the left anterior descending coronary artery. The dissecting aneurysm was treated with patch closure and the RCA was revascularized with a right gastroepiploic artery and saphenous vein composite graft through combined right antero-axillar thoracotomy and lower mini-sternotomy without RITA dissection. Treatment of chronic type A dissection following CABG becomes more challenging with a functional midline crossing RITA. It is important that a safe and less invasive surgical strategy be implemented for such complicated case.

Aged↗
PubMed1996

[Treatment of pseudarthrosis of the clavicle by bone plate with screw fixation and autologous spongiosa graft].

PURPOSE OF THE STUDY: The authors review and evaluate the operative treatment of mid-shaft clavicular non-union by compression plate osteosynthesis and most frequently by decortication and autogenous bone grafting. MATERIAL AND METHODS: From 1979 to 1990, 11 consecutive patients, 9 males and 2 females, mean age 33.5 years, with symptomatic non-union of mid-shaft clavicular fracture were operated and followed-up for an average of 4 years. The pseudarthrosis was atrophic in 10 and hypertrophic in 1 patient. The initial treatment of the fracture was always conservative. RESULTS: All patients achieved bone union by 3-7 months post operatively. The functional results were excellent in 9 patients. The remaining two patients had mild symptoms such as occasional pain related to weather, soreness of the muscles with overhead lifting and discomfort of the shoulder. Minor complications were noted such as 1 delayed wound healing, 3 cheloid scars and 1 transient partial paresis of the brachial plexus. DISCUSSION: Symptomatic non-union of the mid-shaft clavicular is a rare complication, mainly after non-operative treatment (11 cases in 12 years in our series). Factors responsible for non-union are the initial high velocity injury, the cominution, the overlapping and great displacement, the paucity of cancellous bone at this site and the trapezius interposition. Internal fixation by compression plating, decortication and bone grafting in atrophic non-union often encountered is a safe reliable method allowing uncomplicated healing and acceptable functional results.

Adolescent↗
PubMed1984

Effect of hepatic dysfunction on oral cyclosporin pharmacokinetics in marrow transplant patients.

The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporin (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v-host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (less than 1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P less than .05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.

Administration, Oral↗
PubMed1990

Calcium-channel blockers and other factors influencing delayed function in renal allografts.

A retrospective analysis was undertaken to examine the influence of calcium-channel blocking drugs on early renal allograft function. Delayed function was defined as the need for dialysis or a reduction in serum creatinine of less than 15% within 4 days of transplantation. The drug histories of 172 patients were examined. After exclusions, the data from 138 patients were analysed. No patient was taking any calcium-channel blocking drug other than nifedipine. Thirty-one patients were taking nifedipine at the time of transplantation and these had a delayed function rate of 16% compared with 40% for 107 patients not taking nifedipine (chi 2, P less than 0.05). Delayed function occurred in 61% of cases when the donor age was over 50 years compared with 29% with younger donors (chi 2, P less than 0.05). A total ischaemic time of longer than 24 h and administration of inotropic support to the donor were associated with delayed function (chi 2, P less than 0.05). Administration to the donor of mannitol, steroids, phenoxybenzamine and heparin had no effect on the rate of delayed function. Recipients treated with low-dose dopamine in the perioperative period had no advantage. Elevated trough whole blood concentrations of cyclosporin in the first week after transplant were associated with delayed function (Mann-Whitney U, P less than 0.05).

Adult↗
PubMed1982

Experience with immediate and delayed mandibular reconstruction.

The functional disability and cosmetic deformity after jaw and neck dissection can be very severe due to soft tissue and mandibular loss. Reconstruction of the mandible alone without soft tissue coverage can be complicated with prosthetic exposure, infection and, finally, rejection. We attempted to reconstruct the mandible at the time of tumor resection in a group of patients, using titanium mesh with marrow, rib, scapular spine, and clavicle. We used myocutaneous flaps in order to obtain intraoral coverage of the mandibular grafts. In a second group of patients, delayed reconstruction of the jaw was performed 6 months to 2 years after tumor resection. Titanium mesh prostheses were used for reconstruction of the mandible in conjunction with myocutaneous flaps for soft tissue augmentation. Osteomyocutaneous flaps were also used. The results and complications in 54 patients are presented.

Bone Transplantation↗
PubMed1997

Herbert screw fixation for scaphoid nonunions. An analysis of factors influencing outcome.

A retrospective review of 160 cases of scaphoid nonunion treated by internal fixation using a Herbert screw with bone grafting was conducted at an average followup of 24 months. Definite radiographic union was achieved in 90% of cases. Based on Cooney's clinical scoring system, 80 cases had an excellent result, 37 had a good result, 33 had a fair result, and 10 had a poor result. Failure of union was related to the existence of avascular changes of the proximal fragment, instability of the fracture fragment, the prolonged delay in surgery, and the location of the fracture site. In the united scaphoids, the lengthy period of postoperative immobilization, the existence of osteoarthritis, and the prolonged delay in surgery were significant factors in the patient's functional outcome. Overall, the results do not support the view that a residual flexion deformity of the scaphoid is less likely to yield a satisfactory outcome, although it seems worthwhile to correct excessive angulation at the time of repair to promote an anatomic union, thereby preventing early arthritis. A bone graft with internal fixation using a Herbert screw and a shorter period of immobilization may give a satisfactory functional result when the nonunion is treated before the onset of arthritic changes in the wrist.

Adolescent↗
PubMed2005

End-to-side nerve grafting of the tibial nerve to bridge a neuroma-in-continuity.

Standard treatment for a neuroma-in-continuity with partial retained function is neurolysis with or without grafting. The present study tests the outcome of a novel partial nerve lesion bypassed with an end-to-side bridge graft, intended to increase the number of axons crossing the defect while not disturbing intact axons. An 8-mm portion of tibial nerve was resected in 20 rats. Three weeks later, half had the defect repaired with an end-to-side bridge allograft and perineurial windows; controls had only neurolysis. Recovery was evaluated using walking-track analysis, allodynia testing, muscle weight ratios, and histology at 8 weeks. No significant differences in motor or sensory functional recovery were noted between the two groups. Histology showed good axonal regeneration through the defect in all specimens. The experimental group also had regenerated axons in the bridge graft, but their maturity was less advanced, presumably due to delays in regeneration.

Animals↗
PubMed2003

Massive immune hemolysis after non-myeloablative allogeneic peripheral blood stem cell transplantation with minor ABO-incompatibility.

A 35-year-old male, blood group B, Rh(D)+ type, received an allogeneic peripheral blood stem cell (PBSC) transplant after a non-myeloablative regimen of fludarabine and cyclophosphamide for resistant gammadelta cutaneous T-cell lymphoma (CTCL). The donor was his HLA-identical brother, blood group O, Rh(D)+ type. Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporine alone. On day +8, massive immune hemolysis occurred, followed by acute renal failure. Hemodialysis was performed eight times until recovery of renal function on day +24. The risk of delayed immune hemolysis after non-myeloablative allogeneic PBSC transplantation with minor ABO-incompatibility must be considered.

ABO Blood-Group System↗