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Experimental models of small intestinal transplantation in rats: orthotopic versus heterotopic model.

Two kinds of surgical models of small intestinal transplantation (SITx) in rats, namely heterotopic (HIT) and orthotopic transplantion (OIT), have been reviewed. In OIT, the small intestine of the recipient is removed and the transplanted intestine replaces it in continuity. On the other hand, in the HIT model, the small intestinal grafts are rendered dysfunctional without alimentary tract continuity. Histological evidence showed that acute rejection appeared earlier in HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa produced in the chronic rejection process were more pronounced in HIT allografts. The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal trophic factors, because oral feedings can stimulate tropic hormones for mucosal growth, and provide nutrients for enterocytes. Intestinal permeability was consistently higher after HIT than after OIT. The HIT grafts demonstrated less contractility and less response to chemical stimulation than did OIT grafts. The OIT models are advantageous in studies of intraluminal nutrients, and intestinal secretions in these models might modulate the intestinal immune status and possibly delay rejection. The superior intestinal barrier function and the delayed onset of rejection in OIT rats suggest that nutrients and other factors in the succus entericus are important for the maintenance of intestinal graft function.

Animals↗

Primary reconstruction of anterior neck burns with free flaps.

Comprehensive management of acute neck burns is directed towards a satisfactory aesthetic and functional result. Primary microsurgical burn reconstruction of the anterior neck may offer advantages over the traditional technique of skin grafting and delayed reconstruction. It can be indicated in selected patients, obtaining good aesthetic results, with earlier functional recovery and reducing the number of surgical procedures required.

Burns↗

IgG antibody and delayed-type hypersensitivity responses in nude mice grafted with thymic epithelium.

This study compared the ability of foetal thymic epithelium depleted of lymphocytes and dendritic cells, by low temperature or deoxyguanosine (dGuo) treatment in organ culture, to reconstitute T-cell function in nude mice. It is shown that renal capsule grafts of either type could promote the development of functional T lymphocytes in the periphery, as judged by in vivo assays. Both syngeneic and allogeneic thymic epithelium endowed nude mice with the capacity to mount IgG antibody and delayed-type hypersensitivity (DTH) responses to the T-dependent antigen ovalbumin (OVA). Functional reconstitution was accompanied by the appearance of Thy-1-bearing cells in the spleens of thymic grafted nude mice. The results from allogeneically grafted recipients show that a substantial population of peripheral T cells was present that collaborated with B cells and other antigen-presenting cells (APC) which do not express major histocompatibility complex (MHC) molecules of the thymus donor haplotype.

Animals↗

Protective effects of ex vivo graft radiation and tacrolimus on syngeneic transplanted rat small bowel motility.

BACKGROUND: Intestinal transplantation is unduly complicated by the nontolerogenic properties of the gut-associated lymphoid tissue. Because simultaneous graft irradiation and bone marrow infusion significantly prolong the survival of the small bowel transplanted animal, our objective was to determine the functional motility effects of the immune modulating, graft irradiation procedure in the presence and absence of tacrolimus immunosuppression. METHODS: Four groups of syngeneic orthotopic small bowel transplanted animals were studied 48 hours after operations (untreated, tacrolimus, ex vivo graft irradiation, and tacrolimus + irradiation) and compared with controls. Histologic analysis was performed for mucosal apoptosis and neutrophilic infiltration into the muscularis externa. Gastrointestinal in vivo transit and in vitro circular muscle strip contractions were quantified in response to bethanechol (0.3-300 micromol/L). RESULTS: Graft irradiation ex vivo alone or in the presence of tacrolimus significantly increases (> 10-fold) the number of apoptotic mucosal cells after transplantation. Functional measurements showed that transplantation resulted in a significant delay in gastrointestinal transit and a decrease in muscle strip contractility. Tacrolimus and graft irradiation significantly ameliorated the transplant-induced dysfunction. CONCLUSIONS: Given the endowed propensity of mucosal regeneration, the immunologic and functional benefits of ex vivo graft irradiation appear to outweigh the detrimental effects to the mucosa.

Animals↗

Rehabilitation of burn patients with concomitant limb amputation: case reports.

Burn patients with associated limb amputations present demanding rehabilitation problems, many of which might be expected to lead to chronic difficulties. Therapeutic goals following limb amputation include oedema reduction, prevention of contracture (through positioning and range of motion), stump shaping, both pre- and post-prosthetic fitting strengthening exercises of the limb and trunk, and gait training. Some patients present problems that are associated with both the burn injury and the limb amputation that cause concern among the physical therapy staff. Some of these situations include intolerance of the stump to pressure or manipulation due to remaining open wounds or fragility of newly skin grafted areas on the residual limb or delayed gait or functional training due to wounds on other body surface areas. Delays in stump preparation or other treatment aims due to continued surgical procedures can be worrisome. A review of these patients indicates the possible difficulties that rehabilitation personnel may face when treating burn victims who required amputation. Effective rehabilitation of these patients can be achieved despite the noted concerns.

Adult↗

Use of a skin-fat composite graft to prevent alar notching: an alternative to delayed postoperative repair.

BACKGROUND: Full-thickness defects of the alar rim can be challenging to repair and often require the use of multistaged interpolated flaps. Alar notching is a known complication of these procedures even after cartilage batten grafts have been placed to support the alar framework. Standard techniques for repair of alar notching involve reinsertion of a cartilage graft, usually at the time of alar groove reconstruction 3 months postoperatively. OBJECTIVE: We present a technique to prevent alar notching associated with nasolabial interpolation flaps. If early notching is noted at the time of pedicle division, preemptive placement of a skin-fat composite graft can obviate the need for additional procedures. METHODS: A case report detailing the procedure and a review of the options for repair of alar notching are provided. RESULTS. Placement of a skin-fat composite graft harvested from the divided pedicle flap resulted in correction of alar notching. CONCLUSION: This procedure is presented as an alternative to delayed cartilage grafting for repair of alar rim notching after placement of an interpolated pedicle flap. If notching is noted early, correction at the time of pedicle division allows for use of available tissue for composite grafting, avoidance of a delayed reconstructive procedure, and a good functional and cosmetic

Adipose Tissue↗

A case of ABO-incompatible renal transplant patient with non-insulin-dependent diabetes mellitus; long-standing observation of serial glomerular change by protocol biopsy.

A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival.

ABO Blood-Group System↗

[Kinetics of plasma and urine aluminium after renal grafting (author's transl)].

Kinetics of plasma and urine aluminium (Al) were studied prospectively in 40 kidney recipients during 6 months following grafting, including 2 patients with dialysis encephalopathy. Two groups of patients were defined according to graft function outcome. Group I: successful grafting, either immediate (Ia), or delayed (Ib); group II: immediate and definitive graft failure. A control group was added including hemodialysis patients undergoing non-transplantation surgery (without steroid therapy). Recipients of group I excreted high amounts of A1 and progressively normalized their plasma A1 within 6 months (13 Micron g/1 +/- 7 versus less than 10 Micron g/1 in normal subjects). The average A1 excretion during the first month was 9539 Micron g +/- 12.233 Micron in group Ia and 9048 Micron g +/- 4445 Micron g in group Ib. In one encephalopathic patient (group Ia), it even reached 2166 Micron g per day and amounted to 44.727 Micron g during the first month. In all groups taken as a whole, an early period of increase in plasma A1 occurred which was moderate and observed mostly in patients with low initial plasma A1 values (less than 50 Micron g/1) in group Ia, but high and significant (p less than 0.01) in group Ib. This increase was present as well in group II (p less than 0.01) but to a somewhat lesser extent than in group Ib. The mechanism of this sharp increase of plasma A1 in the early period following grafting is not clear. Two major factors are discussed : steroid therapy or A1 (OH)3 ingestion, but there was no correlation between given doses and plasma A1 levels after grafting; persistent hyperparathyroidism which could enhance A1 intestinal absorption.

Adolescent↗

Immuno-modulating properties of interferons.

Interferons (IFNs), by inducing the antiviral state in cells, are in the first line of defence against virus infections and are therefore part of the immune system as defined in its broadest sense. In addition, IFN-alpha and beta can influence specific functions of lymphocytes and macrophages; moreover, a special class of interferons, called IFN-gamma, are produced as a result of antigen recognition by T cells and by the interaction of mitogens and lymphocytes. Interferons influence B and T cell function in vitro and in vivo, as demonstrated by their effects on antibody formation, specific cytotoxicity of sensitized T cells, allograft survival, delayed-type hypersensitivity and graft-host reaction. They stimulate Natural Killer cell activity and induce functional and morphological changes in mononuclear phagocytes. There are many examples of disturbed immune reactions as a result of viral infection, implicating interferons as contributing factors; this is a result of the lack of immunological specificity of interferon action. The extent to which interferons have a truly immunoregulatory role is a question currently receiving a great deal of attention, but is still very much unsettled.

Animals↗

Delayed administration of low-dose NPC18915 ameliorates lung ischemia-reperfusion injury.

BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins (neutrophil activation inhibitors), has been shown to reduce reperfusion injury in rat lung transplantation at high dosage. In vitro studies have demonstrated effectiveness of this compound even at low dosage. We hypothesized that this compound ameliorates lung ischemia reperfusion injury even at low dosage levels if administration is optimally timed. The aim of this study was to determine the efficacy and the best timing for administration of low-dose NPC18915. METHODS: Forty syngeneic rat left lung transplantations were performed. All isografts were flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18 hours at 4 degrees C. Animals were divided into four groups. Group I animals (n = 10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n = 10), NPC18915 (0.04 mg) was added to the flush solution and was administered intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60 minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary function was assessed 24 hours after reperfusion. RESULTS: In group III, oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/- 16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase activity were significantly improved (group III versus group I, 6.02 +/- 0.21 versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019 versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no significant differences in CD11b expression. CONCLUSION: These data suggest that delayed administration of NPC18915, 60 minutes after reperfusion, dramatically improves pulmonary graft function.

Animals↗

Pancreas transplants from donors aged 45 years or older.

AIMS: Since donor age of 45 years or more is considered a relative contraindication for pancreas transplantation (PTx), we herein report our experience with these donors. METHODS: Pancreases from donors aged 45 years or older were used in 16 of 147 PTx procedures (11%). The final decision to accept a graft for PTx was based mainly on the quality of visceral perfusion and the gross appearance of the pancreas and the vessels. There were 9 men and 7 women, ranging in age from 45 to 55 years (average, 48.9 years) who were donors, due to cerebrovascular accidents (n = 11; 68.7%). Among the donor group, 5 patients were receiving multiple vasopressor agents (31.2%), and 2 had a history of cardiac arrest (12.5%). Pancreases were transplanted either simultaneously with a cadaveric kidney (n = 6) or as solitary grafts (n = 10). RESULTS: After a mean period of cold preservation of 616 minutes (range, 475 to 844 min), delayed endocrine function occurred in 1 recipient (6%), who subsequently achieved insulin independence. Two recipients died suddenly, with functioning grafts. Two further grafts were lost due to portal vein thrombosis (6%) or late arterial thrombosis (6%). Three patients required repeat surgery (18.7%). After a mean follow-up period of 26.6 months, actuarial 1-year and 5-year patient survival rates were 87.5%, with insulin independence in 81.2% and 67.7%, respectively. CONCLUSIONS: Meticulous donor selection and short preservation times allow the safe use of pancreases procured from donors aged 45 years or older, thus expanding the donor pool for PTx procedures.

Age Factors↗

An assessment of intrarenal hydrostatic pressure measurements in the diagnosis of acute renal allograft rejection.

Postoperative intrarenal pressure measurements may be an aid to the diagnosis of acute renal transplant rejection, especially in patients treated with cyclosporine. Serial measurements of intrarenal pressure were made in 38 recipients using a fine-needle technique. Thirty-two intraoperative and 207 postoperative measurements were made, and 39 clinical rejection episodes (23 confirmed by biopsy) monitored. Intraoperative pressures in grafts with immediate function (37.4 +/- 4.0 mmHg, mean +/- SEM) were not significantly different from those with delayed function (30.9 +/- 4.8 mmHg), whereas postoperative pressures were greater (P less than 0.01) in kidneys with acute tubular necrosis (29.4 +/- 1.9 mmHg) than in functioning grafts (20.4 +/- 0.9 mmHg). Pressures recorded during clinical rejection episodes (44.3 +/- 2.3 mmHg) exceeded (P less than 0.001) those during quiescent periods (23.6 +/- 1.0 mmHg). During rejection episodes, higher pressures (P less than 0.01) were recorded from tender or palpably enlarged grafts (52.5 +/- 3.0 mmHg) than in the absence of these signs (36.3 +/- 3.1 mmHg), and patients whose transplants biopsies showed cellular rejection tended to have greater pressures (50.1 +/- 4.1 mmHg) than those with concomitant vasculopathy (36.4 +/- 3.9 mmHg), but the latter did not reach statistical significance. In 7 cases of cyclosporine toxicity the intrarenal pressure was 17.8 +/- 4.2 mmHg. Using a diagnostic cut off point of 40 mmHg, the investigation failed to recognize 26% of acute rejection episodes--and, in the presence of acute tubular necrosis, it wrongly categorized 21% of nonrejectors. While its predictive capacity was limited, the test may occasionally be helpful in the differentiation of cyclosporine toxicity and rejection in functioning kidneys.

Acute Kidney Injury↗

"Smile" reconstruction in facial paralysis.

Reanimation of the face following facial nerve paralysis, especially the socially important smile, presents a complex surgical challenge requiring an individualized approach. Both neural and non-neural operative procedures have been used in an attempt to achieve the goal of a symmetrical synchronous smiling expression. A retrospective review of the results of both neural and nonneural methods was made to determine the relative efficacy of various methods. Of the neural techniques, early direct nerve repair primarily consistently achieved the best functional recovery. Double nerve grafts were found to be superior to a single nerve graft in nerve severance with a nerve gap at the facial nerve trunk bifurcation in delayed cases. In long-standing cases, ipsilateral or cross-face nerve grafting followed by functioning muscle transfer gives the most acceptable synchronous smile. Although cross-face nerve graft only, hypoglossal facial transfer, or non-neural techniques such as temporal muscle transfer achieved restoration of the smile, their inconsistent results and asynchronous action still limited the patient's confidence in social interactions.

Facial Expression↗

Positive effect of low molecular weight dextrans on the early graft function.

This study evaluates the effect of the low molecular weight dextrans as a perfusion solution on early graft function of twenty living donor kidneys. Ten kidneys were perfused with +4 degrees C Ringer lactate after nephrectomy while other ten with +4 degrees C Ringer lactate + 10% Dextran. Immediate and delayed kidney function, blood creatinine, postoperative hemodialysis requirement, Doppler US and renal scintigraphy, third month graft survival and number of removed grafts were examined postoperatively as well as kidney biopsies. No statistical difference was found between the groups regarding the post-transplant ATN period. But the microscopic examinations demonstrated less damage-more function in Ringer lactate+Dextran group compared to Ringer lactate alone.

Adolescent↗

Combined grafting of bone marrow and thymus, and sequential multiple thymus graftings in various strains of mice. The effect on immune functions and life span.

The combined grafting of young bone marrow and newborn thymus performed in old mice was effective in restoring the impaired immune functions, but the same treatment performed in middle-aged adult mice had no effect on the life span of C3H/MTV female mice. Sequential multiple newborn thymus graftings starting at young adult age were effective in enhancing immunological functions, delaying the onset of tumor and extending the survival rate to certain degree in the first half of the experimental course in both C3H/MTV as well as C57BL/6 mice, but these effects were not observed in the latter half of the experimental course. It was suggested that multiple newborn thymuses sequentially implanted into the peritoneal cavity underwent atrophy and these atrophic thymuses had a suppressive effect on the host immune system. In autoimmune prone B/WF1 mice, however, the combined grafting of young bone marrow and newborn thymus resulted in suppression of antibody formation to SRBC, and single grafting of either young bone marrow or newborn thymus resulted in a trend of increase in the antibody formation to SRBC. The sequential multiple newborn thymus graftings in B/WF1 mice brought about aggravation of kidney diseases and shortening of the mean life span. On the contrary, administration of thymosin in B/WF1 mice resulted in amelioration of kidney disease and elongation of the mean life span.

Animals↗

The delayed duct occlusion technique of human pancreatic transplantation.

This is a report on a consecutive series of 50 primary human pancreatic transplants performed between 1980 and March 1989. All patients suffered from end-stage diabetic nephropathy, thus all received a kidney graft simultaneously. The basic technique consisted of intraperitoneal placement of a duct-occluded pancreas segment. The main technical and non-immunological complications included primary non-function (10%) because of ischemic damage or technical error, graft pancreatitis (4%), arterial thrombosis (6%) and venous thrombosis (16%). Five patients (10%) died in the later course with functioning transplant, and 10 transplants (20%) were lost due to acute or chronic rejection, 7 of them in the pre-cyclosporin era. The technical modifications introduced during these years to overcome complications consisted of temporary percutaneous drainage of the exocrine secretion for function control, delayed occlusion of the ductal system with polyurethane, and continuous heparin perfusion of the graft in the postoperative period by means of an arterial catheter.

Adult↗

Time-dependent effects of intrahippocampal grafts in rats with fimbria-fornix lesions.

Based on three experiments, this study examined whether behavioral and histological effects of fetal septal or hippocampal grafts placed in the denervated hippocampus depend on the duration of post-grafting delays. Each experiment included four groups of rats: sham-operated rats (Sham), rats with aspirative lesions of the fimbria-fornix (Fifo) and rats given both Fifo lesions and intrahippocampal fetal suspension grafts of either septal (Fifo.ST) or hippocampal (Fifo.HT) origin. All rats were tested (i) for home cage activity, (ii) for activity and reactivity in an open field and (iii) for learning ability in a 8-arm radial maze. Except for home cage activity which was also monitored preoperatively, behavioral tests were conducted between 1-2 months postgrafting in Experiment 1 (EXP1), 5-6 months post-grafting in Experiment 2 (EXP2) and 10-11 months post-grafting in Experiment 3 (EXP3). Each test period lasted 3 weeks. Histological controls consisted of acetylcholinesterase (AChE) and cresyl violet staining. Graft size was estimated by computerized image analysis. Normal rats performed well in each experiment. In all experiments, rats with fimbria-fornix lesions showed increased activity in both their familiar (home cage) and unfamiliar (open field) environments, and their performances in the radial maze task were impaired. In no experiment did grafts, whether hippocampal or septal, affect "noncognitive" behavioral variables. However, maze performance was improved by hippocampal grafts in EXP1 (short delay) and by septal grafts in EXP2 (intermediate delay). No graft-induced effect was found in EXP3 (long delay). Concerning AChE-positivity in the dorsal hippocampus, fimbria-fornix lesions reduced staining densities by at least 60%. Both types of grafts were undiscernably AChE-positive, but only septal grafts provided the denervated hippocampus with a significant AChE-positive fiber ingrowth. Differences among groups in density of hippocampal AChE staining were comparable in all three experiments and no correlation between hippocampal AChE-positivity and maze performance was found. Our results suggest that graft-induced recovery from behavioral effects of fimbria-fornix lesions may depend on both the type of tissue implanted (hippocampal vs septal) and the post-grafting delay (1-2, 5-6 and 10-11 months). The recovery observed at a short post-grafting delay with hippocampal grafts and at a longer post-grafting delay with septal grafts was not persistent and concerned only cognitive function as assessed by radial maze performance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pancreas preservation with University of Wisconsin and Celsior solutions.

BACKGROUND: Although the use of Celsior has been recently described for heart, lung, liver, and kidney transplantation, no data are available on its use for clinical pancreas preservation. METHODS: We herein describe the results of 112 pancreas transplants preserved with either University of Wisconsin (UW; (n = 56) or Celsior (n = 56) solution at two Italian transplant centers. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Mean cold and warm ischemia times were 10.1 +/- 2.2 hours and 37.2 +/- 8.2 minutes for UW compared to 10.8 +/- 2.4 hours and 38.3 +/- 6.7 minutes for Celsior (P = NS). Delayed endocrine pancreas function was recorded in two UW-preserved grafts (3.6%). Actuarial 1-year patient survival was 94.6% for UW as compared with 100% for Celsior (P = NS). Equivalent graft survival figures were 91.0% for UW as compared with 96.4% for Celsior (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and Celsior solutions have similar safety profiles for pancreas transplantation.

Adenosine↗