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PubMed2002

Analysis of the innate and adaptive phases of allograft rejection by cluster analysis of transcriptional profiles.

Both clinical and experimental observations suggest that allograft rejection is a complex process with multiple components that are, at least partially, functionally redundant. Studies using graft recipients deficient in various genes including chemokines, cytokines, and other immune-associated genes frequently produce a phenotype of delayed, but not indefinitely prevented, rejection. Only a small subset of genetic deletions (for example, TCR(alpha) or beta, MHC I and II, B7-1 and B7-2, and recombinase-activating gene) permit permanent graft acceptance suggesting that rejection is orchestrated by a complex network of interrelated inflammatory and immune responses. To investigate this complex process, we have used oligonucleotide microarrays to generate quantitative mRNA expression profiles following transplantation. Patterns of gene expression were confirmed with real-time PCR data. Hierarchical clustering algorithms clearly differentiated the early and late phases of rejection. Self-organizing maps identified clusters of coordinately regulated genes. Genes up-regulated during the early phase included genes with prior biological functions associated with ischemia, injury, and Ag-independent innate immunity, whereas genes up-regulated in the late phase were enriched for genes associated with adaptive immunity.

Animals↗
PubMed1992

Long-term beneficial effects of azathioprine addition to ongoing cyclosporine-prednisone protocol in renal transplantation.

Delayed addition of azathioprine (Aza) to an ongoing cyclosporine-prednisone protocol was started 11.3 +/- 9.9 months after renal transplantation in 31 patients. Group I (n = 10) had chronic renal function deterioration due to chronic rejection, group II (n = 11) had repeated or severe acute rejection episodes and group III (n = 10) had cyclosporine (Cs) toxicity despite drug tapering. In group I, SCr had risen over the 6 months prior to Aza addition (P < 0.05), renal function declining at a rate of -0.13 +/- 0.12 SCr(-1). In the 6 months post-Aza, renal function improved at a rate of 0.05 +/- 0.07 SCr(-1), and during the entire follow-up at a rate of 0.05 +/- 0.12 SCr(-1) (P < 0.01) with stable Cs levels. In group II the decline in renal function was greater, though the rate of decline was stopped after Aza. In group III, renal function improved in eight patients. After 23 +/- 12 months of follow-up, 15 patients had improved graft function, two were stable, 12 had worsened (nine on dialysis) and two had died. Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to Cs-prednisone-treated renal allograft patients with chronic rejection or Cs toxicity, with long-term beneficial effects in a high proportion of patients.

Azathioprine↗
PubMed1985

Fingertip amputation: review of 100 digits.

Evaluation of the functional results and complications of 100 fingertip amputations revealed no difference between the two most commonly used repairs; 52 injuries were treated by primary closure with residual viable skin flaps and 27 by split-thickness skin grafting. No decline in unfavourable functional results was found when patients evaluated 6 weeks after injury were compared to patients evaluated 42 weeks after injury, suggesting that delaying the patient's return to full activity by prolonging rehabilitation is unlikely to yield much improvement. Shortening the nerves in proximal amputations closed by residual flaps did not decrease nerve irritation. Resection of bone produced a mobile amputation-stump tip. While the mean time off work or return to full activity following skin grafting was 6 days less than it was after primary closure, the difference was not significant.

Absenteeism↗
PubMed1993

Contrast examination of the small bowel in patients with small-bowel transplants: findings in 16 patients.

OBJECTIVE: The purpose of this study was to describe the findings on contrast examinations of the gastrointestinal tract in patients with small-intestinal transplants. SUBJECTS AND METHODS: Sixteen consecutive adult transplant recipients received a total of 17 allografts: eight isolated small-bowel, six small-bowel and liver, and three multivisceral (stomach, duodenum, pancreas, small-bowel, liver). Grafts included the entire mesenteric small bowel. Gastrointestinal contrast studies were done in asymptomatic patients according to protocol and in patients having clinical indications for examination. Median time from transplantation to examination was 78 days (range, 5-768 days). Seventy-five gastrointestinal contrast examinations were performed: 53 upper gastrointestinal and small-intestinal series, 12 upper gastrointestinal series, eight enteroclyses, and two water-soluble contrast enemas. Radiographs were analyzed for postsurgical anatomy, integrity of anastomoses, allograft radiologic appearance, small-bowel transit time, and rate of gastric emptying. RESULTS: Usual postsurgical anatomy included native-to-donor duodenojejunal, jejunojejunal, and gastrogastric anastomoses and donor-to-native ileocolonic and ileoileal anastomoses. No anastomotic complications were found. Leaks at native duodenal and colonic stumps resulted in a duodenocutaneous fistula and an abscess, respectively. Moderate to marked thickening of mucosal folds consistent with edema was present in nine allografts (53%) and 11 (17%) of 66 upper gastrointestinal and small-intestinal examinations, primarily in the early postoperative period. Chronic loss of allograft mucosal folds developed in four grafts in three patients; pathologic diagnoses included acute and chronic rejection and enteric infection; a jejunocutaneous fistula developed in one such patient. Transit times of barium through the small intestine ranged from 0.2 to 17.8 hr (median, 2 hr). Self-limited delayed gastric emptying was present in 14 patients (88%) and 32 (60%) of 54 upper gastrointestinal and small-intestinal examinations. CONCLUSION: Gastrointestinal contrast examinations in recipients of small-bowel transplants are useful for assessing graft anatomy, enteric anastomoses, and gastrointestinal motor function. Most intestinal grafts showed normal caliber and mucosal pattern and exhibited active peristalsis. Abnormal findings included self-limited postoperative edema of graft mucosal folds, chronic loss of the mucosal folds due to rejection and/or enteric infection, delayed gastric emptying that improved with time, leaks from native duodenal and colon stumps, and a jejunocutaneous fistula in a failing graft. Small-intestinal transit times were similar to those observed in patients not receiving transplants, although there was wide variation.

Adult↗
PubMed2005

[Immunologic reconstitution after allogeneic stem cell transplant].

Patients submitted to allogeneic stem cell transplantation have a prolonged immunodeficiency, extending beyond one year post-transplant. The immune reconstitution after an allogeneic stem cell transplant is dependent upon several factors, such as the age of the recipient, the degree of in vivo or in vitro T-cell depletion, the emergence and eventual treatment of graft versus host disease. While neutrophils and NK cells recover normally within 2 months of transplant, the reconstitution of B- and T-cell immunity is significantly slower. In fact, it is impossible to dissociate the emergence of new B-lymphocytes from thymopoiesis, which appears to be determinant for the normal reconstitution of acquired immunity post-transplant. The serial analysis of T cell counts and its subsets, as well as T-cell function and, more recently, of T-cell receptor excision circles, show a delay in T-cell reconstitution in adult patients, patients with extensive chronic graft versus host disease and in the first 9 months post-transplant in recipients of T-cell depleted grafts. The incidence of opportunistic infections is higher in this population. Therefore, with the aim of reducing post-transplant mortality, the development of new strategies for the acceleration of immune reconstitution is crucial. One possibility is the use of adoptive cellular immunotherapy with donor leukocytes in order to boost the incipient donor's immune system in the receptor. Preliminary studies in animal models also suggest that interleukin-7 and keratinocyte growth factor improve thymopoiesis, thereby stimulating the immune reconstitution post-transplant.

B-Lymphocytes↗
PubMed2005

Differentiation and functional connection of vascular elements in compatible and incompatible pear/quince internode micrografts.

Micrografts of internodes excised from in vitro grown pear plants (Pyrus communis L. cv. 'Bosc' (B) and cv. 'Butirra Hardy' (BH)) and quince (Cydonia oblonga Mill. East Malling clone C (EMC)), were cultured aseptically to test the effectiveness of their functional vascular reconnection in relation to incompatibility-compatibility relationships that these genotypes exhibit in the field. The incompatible heterograft (B/EMC) showed a marked delay in internode cohesion compared with the autografts (both B/B and BH/BH) and the compatible heterograft (BH/EMC). Even when fused, the translocation of [14C]-sorbitol from upper to lower internode was lower in B/EMC micrografts than in the other combinations. Epifluorescence studies performed with carboxyfluorescin, a specific phloem probe, indicated that the limited translocation was caused by a delay in the establishment of functional phloem continuity between the two internodes. In the B/EMC combination, new differentiated tracheary elements (TE) in the parenchyma tissue at the graft interface between the two internodes were not detected until 30 days after grafting, whereas in the BH/EMC heterograft and both autografts, new xylem connections appeared to cross the interface 20 days after grafting. Immunohistochemical detection (terminal nick-end labeling assay) of the number of cells undergoing nuclear DNA fragmentation at the graft interface confirmed that the limited and delayed TE differentiation in B/EMC heterografts was associated with a decrease in the activity of programmed cell death processes involved in the differentiation of TE.

Apoptosis↗
PubMed1996

[Effect of complement modulation with the soluble complement receptor sCR1 on survival and function of kidney xenotransplant. An experimental study with a new guinea pig to rate transplant model].

In this study a modified experimental kidney xenograft model was developed, which reproduced, in a reliable way, the course of hyperacute rejection. In this model guinea-pig kidneys were transplanted to rats using end-to-side anastomoses with recipient aorta and vena cava, respectively, and ureter drainage for diuresis monitoring. The aim of this study was to investigate the protective effects of complement modulation by soluble complement receptor 1 (sCR1) on the xenografts. Twenty-four xenotransplantations were performed and recipients randomized for treatment either by 3 ml saline or 50 mg/kg sCR1 as a 3-ml bolus. It was found that sCR1 was highly efficient in delaying hyperacute rejection from 10.5 +/- 2.1 min in the control group to at least 2 h in the therapy group and in prolongation of graft function. The complement activity was significantly reduced in the sCR1-treated rats, even at the time of rejection, as a result of complement modulation in this group of xenograft recipients. Xenografts from saline-treated animals showed necroses, interstitial haemorrhages and platelet aggregates occluding the vessels as soon as 10 min after the reperfusion started. No such changes could be seen even after 120 min in the xenografted kidneys of sCR1-treated rats. Also C3 deposits in the glomeruli and interstitium were markedly reduced.

Animals↗
PubMed1987

Enhanced AKR leukemogenesis by the dual tropic viruses. II. Effect on cell-mediated immune responses.

We examined the relationship of the leukemia-accelerating properties of a dual-tropic virus (DTV-70) (when injected into the thymus of 14-day-old AKR mice) to its ability to impair T cell functions. Splenic lymphocytes from virus-infected AKR mice were found to have reduced T cell mitogenic responses; moreover, these cells suppressed phytohemagglutinin stimulation of cells from normal, uninfected AKR mice. The response to the B cell mitogen lipopolysaccharide was slightly enhanced at 15 days following DTV-70 infection and was unaffected at later ages. AKR mice infected with DTV-70 showed reduced ability to develop delayed-type hypersensitivity reaction and interleukin 2 production. In contrast, spleen cells from the virus-infected mice responded normally to allogeneic stimulation in mixed lymphocyte culture and mounted an almost normal graft versus host reaction. The data suggest that DTV-70 impairs certain T cell functions that could interfere with immune surveillance and thus permit progression of preleukemic cells into overt leukemia. These T cell functions are suppressed normally by 6 months of age, perhaps by spontaneously arising DTV.

Age Factors↗
PubMed1998

Kidney transplantation: the use of living donors with renal artery lesions.

PURPOSE: A shortage of organs for transplantation has forced surgeons to optimize the use of marginal organs, such as kidneys with arterial disease. We present a retrospective study of the outcome of donors with renal artery disease and recipients of kidneys from living related and unrelated donors. MATERIALS AND METHODS: Kidneys with vascular abnormalities from healthy living donors were grafted into 11 recipients. These kidney transplants comprised 1.8% of those performed at our institution. The vascular abnormalities were aneurysms in 3 cases, atherosclerotic lesions in 4 and fibromuscular dysplasia in 4. After nephrectomy all abnormalities were corrected under hypothermic conditions during bench surgery except in 3 cases of ostial atherosclerotic plaque, which was left in the donors. The renal artery was anastomosed to the external iliac artery in 5 cases and to the internal iliac artery in 6. The ureter was reimplanted using an extravesical technique. RESULTS: All patients had immediate diuresis and no delayed post-transplant graft dysfunction was observed. One patient died of an unrelated cause and 3 had post-transplant graft function loss due to acute vasculopathy in 1, post-diarrhea with acute arterial thrombosis in 1 and recurrence of the hemolytic-uremic syndrome in 1. All remaining patients are well with median serum creatinine of 1.4 mg./dl. (normal 0.4 to 1.4). All donors are well and normotensive with normal renal function. CONCLUSIONS: The use of kidneys with arterial disease from living donors with unilateral disease is safe. Complete informed consent regarding the risks and benefits by donor and recipient is mandatory.

Adult↗
PubMed1992

Renal haemodynamic, hormonal and excretory effects of low-dose atrial natriuretic factor infusion in renal transplant recipients.

1. In experimental studies, activation of renal sympathetic nerves attenuates the natriuretic response to atrial natriuretic factor. We therefore investigated the response to low-dose infusion of atrial natriuretic factor in renal transplant recipients. 2. Eight male cyclosporin-treated renal transplant recipients received human-alpha atrial natriuretic factor (1-28) at a dose of 1.2 pmol min-1 kg-1 or placebo for 2 h in a placebo-controlled, randomized, cross-over study. The plasma atrial natriuretic factor concentration rose from 18.5 to 49.2 pmol/l in association with an immediate natriuresis (a rise of 49.1 mumol/min in the first 30 min, P less than 0.05; peaking at a 61% increase from baseline, P less than 0.01), diuresis (from 3.37 to 7.46 ml/min) and a threefold rise in urinary cyclic GMP excretion. 3. In response to infusion of atrial natriuretic factor, the packed cell volume rose by 4.2% (P less than 0.001) and the filtration fraction by 5% (from 22 to 27%, P less than 0.05), but there was no significant change in renal plasma flow, glomerular filtration rate or mean arterial blood pressure. Likewise, the plasma catecholamine concentrations, plasma renin activity and serum erythropoietin concentration remained unchanged. 4. The sensitivity of the renal allograft to plasma atrial natriuretic factor concentrations in the high physiological range suggests a role for endogenous atrial natriuretic factor in the modulation of graft function. Furthermore, the immediate natriuretic response to atrial natriuretic factor in the effectively denervated transplant kidney, in contrast to the delayed response seen in normal subjects, may imply that sympathetic nerves have an inhibitory effect on the renal response to atrial natriuretic factor in normal man.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1997

Short and long distance spread of potato leafroll luteovirus: effects of host genes and transgenes conferring resistance to virus accumulation in potato.

Potato leafroll luteovirus (PLRV) movement through phloem of PLRV-resistant potato clones was examined in experiments in which stem pieces were grafted either between infected rootstocks and virus-free susceptible scions or between infected scions and virus-free susceptible rootstocks. These test plants permitted either upwards or downwards virus movement into the susceptible tissue. Resistant potato clones had either host gene-mediated resistance (H-MR) or transgene-mediated resistance (T-NR, conferred by transformation with the PLRV coat protein gene) to PLRV accumulation. The rate of PLRV movement was similar whether stem tissue was taken from H-MR, T-MR or susceptible potato clones. Virus movement through two graft unions began around 7 days after grafting and was generally complete by about 14 to 16 days. Virus movement occurred soon after acquiring functional phloem continuity across grafts as demonstrated by tracing with 6(5)-carboxyfluorescein, a phloem-mobile dye. Most of the delay in virus detection after grafting probably resulted from the time necessary to develop new phloem strands across graft unions; subsequent movement of PLRV was rapid suggesting a passive process. PLRV infection was largely excluded from external phloem bundles in stem tissue of clones with either H-MR or T-MR. This trait was less pronounced as tissue aged. The mechanism limiting PLRV invasion of external phloem bundles of the T-MR clones appears to be similar to that operating in the H-MR clones. Results are discussed in the context of a proposed model of PLRV movement.

Antigens, Viral↗
PubMed2000

Management of anterior segment penetrating injuries with traumatic cataract by Pentagon approach in paediatric age group: constraints and outcome.

PURPOSE: To evaluate the efficacy of multiple combined procedure (Pentagon approach) as single-step secondary repair in cases of extensive keratolenticular trauma in paediatric age group. METHODS: Retrospective evaluation of 18 patients of penetrating injuries with sclerokeratolenticular trauma, who underwent multiple procedure as single-step secondary repair by a single team of two surgeons during a 4 year period. Surgical procedure included reconstruction of anterior segment, synechiolysis, excision of membrane, lensectomy, open sky vitrectomy, PC IOL implantation over frill and penetrating keratoplasty. Meticulous antiamblyopia measures were applied in all cases. RESULTS: Extensive vasoproliferative membrane, complicated cataract and anterior vitreous condensation were significant intra-operative hurdles. Moderate uveitis, secondary glaucoma, persistent epithelial defects were problems noted. Eleven (61.22%) patients attained good visual outcome. Regrafting was required in remaining cases due to delayed graft failure. CONCLUSION: Despite being a highly complex technique, Pentagon approach provides effective management profile in terms of graft success and functional outcome, especially in keratolenticular trauma, in children.

Amblyopia↗
PubMed1991

Interlocking intramedullary nailing for supracondylar and intercondylar fractures of the distal part of the femur.

Thirty-seven fractures of the distal part of the femur in thirty-five patients were treated with interlocking intramedullary nailing. All fractures were nailed by a closed technique after any intercondylar extension of the fracture had been managed by reduction and stabilization with percutaneous lag-screws. Patients who had an isolated condylar fracture or a severely comminuted intercondylar fracture were treated with other types of implants. There were thirty extra-articular (type-A) fractures and seven intra-articular (type-C1 and type-C2) fractures. Postoperatively, early mobilization exercises and weight-bearing were begun. At an average duration of follow-up of 20.5 months (range, fifteen to twenty-six months), all thirty-seven fractures had healed. There were no malunions of either the supracondylar or the intercondylar fractures. Complications were infrequent and included chronic irritation from the distal screws in three patients and delayed union in one; the latter healed with two centimeters of shortening after bone-grafting. There were no infections. The functional results were assessed with the modified knee-rating system of The Hospital for Special Surgery. Thirteen knees (35 per cent) had an excellent result; twenty-two (59 per cent), a good result; and two (5 per cent), a fair result. The results correlated with the age of the patient and the presence of an intra-articular fracture. We concluded that closed interlocking intramedullary nailing is an excellent technique for both supracondylar and simple intercondylar fractures in which closed reduction and percutaneous fixation of the articular fracture is possible.

Adult↗
PubMed1985

Repair of the flexor pollicis longus.

There are more repair techniques available for an injured flexor pollicis longus than for the other digital flexors. The procedure of choice is immediate primary or early delayed repair (less than three weeks after injury) by direct end-to-end suture. Good thumb function can also be obtained with the use of late delayed repair by tendon advancement with or without lengthening, free tendon grafting, and tendon transfer.

Humans↗
PubMed1995

Obstetrical palsy: early treatment and secondary procedures.

Obstetrical palsy has been described since a long time. Unfortunately, until the last 20 years, few options were available to correct its sequelae. During the last two decades, there has been a regain of interest because of the possibility to microsurgically repair these lesions. Tassin in 1984 demonstrated that babies who have no recovery of the biceps function by three months of age should be operated without delay. At brachial plexus exploration, in the presence of neuroma, nerve grafting is usually necessary. In cases of root avulsion, internal or external neurotization should be performed depending on the severity of the lesions. Physiotherapy and long-term follow-up of these patients are primordial to prevent joint ankylosis and to identify the patients who will benefit from secondary surgery. Our results are presented either after early treatment or after secondary procedures. These results justify aggressive management of obstetrical brachial plexus palsy because of children's great capacity for regeneration and accommodation.

Ankylosis↗
PubMed1998

Efficacy of endoventricular patch plasty in large postinfarction akinetic scar and severe left ventricular dysfunction: comparison with a series of large dyskinetic scars.

BACKGROUND: Many believe that dyskinesia is the only predictor of favorable surgical outcome after large myocardial infarction and that akinetic scars do not recover well in patients with globally depressed ventricular function. METHODS: This study evaluates clinical and hemodynamic results of endoventricular circular patch plasty in patients with either large akinetic scar (n = 51) or large dyskinetic scar (n = 49) and depressed left ventricular function (ejection fraction <30%). Groups were comparable for symptoms, indication for operation, and delay from myocardial infarction. Heart failure was a major indication for operation in both groups. Coronary grafting was performed in 98% of patients: 10 had mitral valve repair or replacement, and 47 patients with preoperative ventricular arrhythmias had cryotherapy. In-hospital mortality was 12% (five patients in the akinetic group [10%] and seven in the dyskinetic group [14%]). RESULTS: Results showed an early and late improvement in New York Heart Association functional class and ejection fraction (from 23% +/- 5% to 31% +/- 11% to 40% +/- 13% in akinetic patients and from 23% +/- 6% to 41% +/- 10% to 41% +/- 12% in dyskinetic patients). Ventricular tachycardia was reduced significantly in both groups early and late after the operation. CONCLUSION: We conclude that in patients with either large akinetic or dyskinetic scar and severe left ventricular dysfunction, endoventricular circular patch plasty associated with coronary grafting and cryotherapy, when indicated, provides surviving patients with significant improvement in cardiac function. This approach can be considered as an alternative to heart transplantation in patients with severe left ventricular dysfunction.

Cardiac Output↗
PubMed1986

The dependence of nerve regeneration through muscle grafts in the rat on the availability and orientation of basement membrane.

Nerve regeneration through grafts of basement membrane matrix, prepared by freezing of autogenous muscle followed by thawing in distilled water, was investigated in Sprague-Dawley rats. Electrophysiological evidence of recovery in distal nerve was observed at 51 days after implantation of treated grafts whose basement membrane tubes were coaxial with the proximal and distal ends of the transected sciatic nerve. This correlated with histological findings of well-developed myelinated nerve fibres within both grafts and distal nerve. However, whereas normal axon numbers were achieved in the grafts by 3 months, the regenerating nerve in these muscle grafts took 6 months to 1 year to recover normal axon diameter and myelination. Recovery was delayed through grafts whose basement membrane tubes were at right angles to the nerve fibres and through grafts of untreated muscle coaxially aligned. It is concluded that successful repopulation of the distal stump and functional recovery can follow nerve regeneration through treated muscle autografts. The rate of regeneration is dependent on the availability of empty basement membrane tubes. If these are unavailable or inappropriately orientated, regeneration can still occur but is significantly delayed.

Animals↗