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PubMed2005

Missile-caused complete lesions of the peroneal nerve and peroneal division of the sciatic nerve: results of 157 repairs.

OBJECTIVE: There are few large-volume studies of the repair of complete missile-caused peroneal nerve and peroneal division lesions. In this prospective study, the outcomes of such repairs are studied and the factors influencing the outcomes are analyzed. METHODS: During a 3-year period, 157 patients with complete missile-caused lesions of the peroneal nerve or peroneal division were treated surgically in the Belgrade Military Medical Academy: 37 patients with high-level (above the middle of the thigh), 90 patients with intermediate-level (above the popliteal crease), and 30 patients with low-level repairs. After at least 4 years of follow-up, outcome was defined on the basis of motor recovery, neurophysiological recovery, and patient judgment of the quality of outcome (poor, insufficient, good, or excellent). Good and excellent outcomes were considered successful. The factors of repair level, defect length, manner of repair, preoperative interval, severity of tissue damage in the repair region, and patient age were studied for their effect on outcome. RESULTS: A successful outcome was obtained in 10.8% of high-level repairs, 31.1% of intermediate-level repairs, and 56.7% of low-level repairs (P < 0.001). Nerve defect and preoperative interval were significantly shorter for patients with a successful outcome compared with those with an unsuccessful outcome (P< 0.001). Worsening of the outcome began with the nerve defect larger than 4 cm and preoperative interval greater than 3 months (P< 0.001). Severity of local tissue damage significantly influenced the outcome (P= 0.008). Repair level (P< 0.001), preoperative interval (P= 0.001), severity of local tissue damage (P= 0.011), and length of nerve defect (P= 0.011) were independent predictors for a successful outcome. CONCLUSION: After peroneal nerve or peroneal division repairs, a successful outcome is most probable with low-level lesions repaired in the first 3 months after injury using grafts smaller than 4 cm. Conversely, high-level repairs delayed for more than 7 months after injury and using grafts larger than 8 cm are probably not worthwhile.

Adolescent↗
PubMed1976

Correction of severe combined immunodeficiency by fetal liver cells.

As an alternative to bone-marrow transplantation, two infants with severe combined immunodeficiency who had no histocompatible donors were given intraperitoneal infusions of fresh liver cells from fetuses of eight and nine to 10 weeks. Transient graft-versus-host disease began at 42 and 52 days, respectively. Both infants had rises in T cells and declines in B cells by three months. No functional immunologic improvement occurred in the first infant, who died of pulmonary disease 10 months later. Clinical and functional immunologic improvement occurred in the other, who is now 19 months after transplantation. Lymphocyte responses to phytohemagglutinin and pokeweed mitogen were noted by three months, to concanavalin A by five months, and to allogeneic cells by eight months. Delayed cutaneous responsiveness to candida developed and IgM became norma. IgA and IgG remained low. Chimerism was demonstrated by a donor marker chromosome in metaphases from recipient lymphocytes. Fetal liver cells therefore reversed the immunodeficiency.

B-Lymphocytes↗
PubMed1993

The determination of dual pancreatic and renal transplant graft vascular patency with Tc-99m HMPAO.

Combined pancreatic-renal transplants promise the restoration of physiologic control of serum glucose and normal renal function. As pancreatic transplantation becomes more common, there is an increased need for rapid, noninvasive evaluation of vascular graft patency and function. Pancreatic transplants share the renal transplant's complications of ischemia at harvest but are at greater risk. Tc-99m HMPAO is a lipophilic complex that clears rapidly from the blood after intravenous injection, and tissue accumulation is proportional to regional perfusion. Using Tc-99m HMPAO to monitor the vascular competency has the advantage of a high count rate during dynamic scintigrams but, in contrast to Tc-99m DTPA, has excellent delayed static images. Four patients who received combined cadaveric pancreatic-renal transplants and had a total of eight Tc-99m HMPAO scintigraphic examinations were reviewed.

Adult↗
PubMed2003

Fibrin-mediated protection against infection-stimulated immunopathology.

Fibrin, a product of the blood coagulation cascade, accompanies many type 1 immune responses, including delayed-type hypersensitivity, autoimmunity, and graft rejection. In those settings, fibrin is thought to exacerbate inflammation and disease. Here, we evaluate roles for coagulation during infection with Toxoplasma gondii, a pathogen whose control requires robust type 1 immunity. We establish that fibrin prevents infection-stimulated blood loss, thereby performing a protective function that is essential for survival. Remarkably, fibrin does not simply protect against vascular damage caused directly by the infectious agent, but rather, protects against hemorrhage evoked by interferon-gamma, a critical mediator of type 1 immunity. This finding, to our knowledge, is the first to document a beneficial role for coagulation during type 1 immunity, and suggests that fibrin deposition protects host tissue from collateral damage caused by the immune system as it combats infection.

Animals↗
PubMed1993

Relationship between donor renal interstitial surface and post-transplant function.

Forty-three biopsies were performed between 30 and 60 min after reperfusion. Patients (22 males/21 females, mean age 41 +/- 12 years, mean donor age 32 +/- 14 years) were treated either with antilymphocytic globulin, cyclosporin, and prednisolone (24 cases), or OKT3, cyclosporin, and prednisolone (19 cases). Ten patients had delayed post-transplant renal function (DPRF), defined as haemodialysis requirements after surgery, and seven patients had acute rejection 11 +/- 16 days post-transplant. Kidneys were perfused with a hypertonic solution containing mannitol. All patients were followed up for at least 30 months. During follow-up, five patients lost their grafts due chronic rejection, two patients due to noncompliance and one due to recurrence of focal segmental glomerulosclerosis. One patient died from heart infarction. Biopsies were stained with H&E, Masson's trichrome, periodic acid-Schiff (PAS) and silver methenamine. Interstitial fibrosis, interstitial oedema, tubular vacuolization, and peritubular capillary oedema were measured using a semiquantitative scale. Five 400 x magnification micrographs of cortical interstitium from silver-methenamine-stained sections were used to measure percentage of interstitial surface with a morphometer. Interstitial surface was 18.7 +/- 6.2% (range 3.2-35.3%). A positive correlation was found between interstitial surface and donor age (r = 0.469, P = 0.0015). No relationship was found between warm and cold ischaemia times and tubular vacuolization or peritubular capillary oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1979

Antithymocyte globulin (ATGAM) in renal allograft recipients. Multicenter trials using a 14-dose regimen.

Antithymocyte globulin (ATG, ATGAM; The Upjohn Company) was tested for efficacy and safety in controlled studies in 358 renal allograft recipients. A total of 183 patients were treated according to protocols prescribing 14 daily doses of ATG in addition to standard immunosuppressive therapy with azathioprine and prednisone, while 175 controls received no ATG. Four ATG lots were tested; results with each lot were analyzed separately, and the data were also pooled to obtain an overall impression. ATG delayed the onset of the first rejection episode during the prescribed treatment period (2 weeks). Concurrently, less i.v. steroid was required, but the steroid dosage requirement then rebounded in the 2 weeks after the end of the prescribed treatment period. ATG did not significantly improve the proportion of patients alive with functioning grafts 6 months after transplant, except with one of the four lots.

Adult↗
PubMed1998

In vivo immunogenicity of purified allogeneic hepatocytes in a murine hepatocyte transplant model.

BACKGROUND: It has been reported previously that liver grafts and liver cells seem to be tolerogenic, based on the high frequency of spontaneous tolerance after orthotopic liver transplantation in rodents and on the phenomenon of portal venous tolerance in other models. The purpose of the current study was to characterize in vivo immune responses to allogeneic hepatocytes transplanted into the portal circulation. METHODS: In this functional model of hepatocyte transplantation, "donor" hepatocytes from mice transgenic for human alpha1-antitrypsin (hA1AT) were transplanted by intrasplenic injection into host mice and the secreted hA1AT protein measured in host serum to determine hepatocellular graft survival. Host immune responses were assessed by measurement of donor-specific alloantibodies and delayed-type hypersensitivity responses. In some experiments, liver nonparenchymal cells (NPCs) were co-transplanted with the allogeneic hepatocyte transplant. RESULTS: Allogeneic hepatocyte transplant into immunocompetent hosts resulted in loss of host serum hA1AT by days 7-10 after transplant, whereas syngeneic hosts maintained long-term hepatocellular graft survival as reflected by persistence of serum hA1AT for > 20 weeks. Allogeneic hepatocyte transplantation resulted in the development of donor-specific alloantibody and delayed-type hypersensitivity responses, as well as a "second set" response of accelerated hepatocellular graft rejection after a second transplant. Pretransplantation or co-transplantation of donor-matched liver NPCs at the time of allogeneic hepatocyte transplantation did not prolong hepatocellular allograft survival. CONCLUSIONS: Allogeneic hepatocytes introduced into the portal circulation via intrasplenic injection are immunogenic not tolerogenic and stimulate a weak humoral and strong cell mediated host immune response in vivo. Co-transplantation or pretransplantation of allogeneic liver NPCs did not protect allogeneic hepatocytes from immunologic rejection.

Animals↗
PubMed1987

Influence of normal central venous pressure on onset of function in renal allografts.

The central venous pressure was kept above 5 cmH2O during the perioperative and early postoperative period as guidance for fluid replacement in 31 patients receiving a renal graft (group B). In 30 other transplant recipients the central venous pressure was not measured (group A). The two groups were otherwise comparable. Onset of graft function within the first 3 postoperative days was significantly more frequent in group B than in group A (62% vs. 30%), despite absence of difference in the measurable warm and cold ischemic periods. Fluid replacement guided by the central venous pressure thus is concluded to reduce the number of kidneys with delayed function in the immediate postoperative period.

Body Weight↗
PubMed2001

The use of skin grafts for nasal lining.

The satisfactory replacement of missing nasal lining often determines the aesthetic and functional result of a nasal reconstruction. Although full-thickness skin grafts have been employed for lining in the prefabricated forehead flap technique, the results are unpredictable because they remain largely unsupported and subject to contraction. Advances in the understanding of the vasculature of the forehead flap, the use of primary and delayed cartilage grafts, and the appropriate use of operative staging permit full-thickness skin grafts to be combined with a forehead flap at the time of transfer, with little risk of loss. The technique is especially useful in the elderly or debilitated patient when a shortened operative time and less intranasal manipulation is appropriate, or when previous injury or rhinoplasty has interfered with septal blood supply, making the use of intranasal lining flaps unreliable.

Humans↗
PubMedDate not supplied

Selective suppression of tumour-immune cytolytic T lymphocytes in mice with chronic Trypanosoma cruzi infections.

Trypanosoma cruzi is the causative agent of Chagas' disease in man, often leading to suppression of T lymphocyte functions; the present study thus considered the effects of infection by T. cruzi on T-dependent immune responses in a murine model, namely, the immune resistance to a syngeneic tumour and a delayed-type hypersensitivity reaction to sheep red blood cells (SRBC). In BALB.B mice infected with T. cruzi, the graft of syngeneic Gross murine leukaemia virus-induced tumour cells leads to an increased incidence of progressive subcutaneous tumours and development of lymphatic leukaemia. This decreased resistance to tumours correlates with a suppression of the generation of tumour-specific cytolytic T lymphocytes (CTL) from the pre-CTL stage. In contrast, clonal expansion and circulation of T cells detected through their ability to locally transfer a delayed-type hypersensitivity (DTH) reaction to SRBC remained normal in T. cruzi-infected mice. However, at the site of the DTH reaction, a decreased availability of phagocytes was observed in T. cruzi-infected mice.

Animals↗
PubMed2000

Preparing a hemimandibulectomy patient for delayed reconstructive surgery.

A rehabilitation device was designed and used before a reconstructive orthognathic procedure in an adult patient with a severe facial asymmetry. The asymmetry developed as a result of a left hemimandibulectomy in childhood. With this prototype device, the remaining hemimandible was gradually brought into its natural position and dynamics in order to accommodate a graft. The goals were to improve esthetics and function, reduce the chance of the remaining hemimandible not adapting to the graft, and reduce the risk of secondary TMJ pathosis after the mandibular reconstruction.

Adult↗
PubMed2000

Regrowth of acute and chronic injured spinal pathways within supra-lesional post-traumatic nerve grafts.

The present work investigates the extent to which mature central neurons acutely or chronically axotomized by a spinal lesion still maintained the potential to regenerate an axon following post-traumatic nerve grafting within supra-lesional spinal structures. In adult rats, a C3 cervical hemisection (injury) was made and an autologous segment of the peroneal nerve was implanted 2mm rostrally into the ventrolateral part of the ipsilateral C2 spinal cord. Nerve graft implantations were carried out acutely at the time of injury (group I, acute conditions) or chronically, three weeks post-injury (group II, chronic conditions). Central neurons axotomized by the spinal lesion were labeled by True Blue injected at the lesion site at the time of trauma. Central neurons regenerating axons within the nerve grafts were labeled with either horseradish peroxidase (only in group I, n=4) or Nuclear Yellow (group I, n=3 and group II, n=6) applied two to four months post-grafting to the distal cut end of the nerve grafts. Neurons with dual staining (True Blue/Nuclear Yellow) represented central regenerating neurons which were previously axotomized by the spinal lesion and which had retained the capacity for axonal regeneration for a delayed period after injury. In group I (acute injury conditions), all types of labeled cells were found to be scattered with a clear bimodal distribution within the spinal cord and the brainstem. No labeled cells were found within the motor cortex. There was no statistically significant difference between horseradish peroxidase and all cells containing Nuclear Yellow (Nuclear Yellow and True Blue/Nuclear Yellow). In group II (chronic injury conditions), Nuclear Yellow- and True Blue/Nuclear Yellow-labeled cells had a similar dual distribution to that of group I, but were found to be significantly less represented (P=0.019). These differences are discussed in terms of capacity for cell survival and axonal regrowth after acute and chronic injury. The main conclusion is based on the evidence of dual staining of central neurons in both groups, which demonstrates that brainstem and spinal neurons involved in acute and chronic axotomy after spinal C3 lesion can survive the trauma and still maintain the capacity to regenerate lesioned axons within nerve grafts inserted rostrally (C2 spinal cord) to the primary site of injury. Although exhibited to a lesser extent in chronic than in acute conditions, this capacity was found to occur for as long as three weeks post-injury. These results indicate that supra-lesional post-traumatic nerve grafts may constitute an efficient delayed strategy for inducing axonal regrowth of chronically axotomized adult central neurons. We suggest that surgical intervention, which is not always possible immediately after a spinal cord injury, may be satisfactorily carried out after an appropriate delay.

Animals↗
PubMed1991

[Infants born to kidney transplant recipients].

Over a period of 24 years, 23 women who had undergone renal transplantation gave birth to 26 children whose gestational ages were above 28 weeks. The average duration of stable kidney function tests before the onset of pregnancy was 34.5 months (6 to 109 months). Immunosuppressive treatment consisted mostly of azathioprine and steroids (20/26), steroids and cyclosporin A (CyA) in one case, and azathioprine, steroids and CyA in 5 cases. Average gestational age at birth was 35.2 weeks (30-40 weeks), average birth weight was 2,330 g (1,160-3,700 g). Caesarean section was performed in 73% of cases. The most frequent neonatal pathological condition was the occurrence of respiratory distress, most often related to prematurity and the mode of delivery. No child presented with any lethal congenital malformation. Children born to mothers who were given CyA did not present with more congenital malformations or renal function impairment.

Adult↗
PubMed2007

Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat.

The goal of this study was to ascertain whether olfactory ensheathing cells (OECs) were able to promote axonal regeneration and functional recovery when transplanted 45 days after complete transection of the thoracic spinal cord in adult rats. OECs promoted partial restitution of supraspinal pathways evaluated by motor evoked potentials and modest recovery of hindlimb movements. In addition, OEC grafts reduced lumbar reflex hyperexcitability from the first month after transplantation. Histological results revealed that OECs facilitated corticospinal and raphespinal axons regrowth through the injury site and into the caudal spinal cord segments. Interestingly, raphespinal but not corticospinal fibers regenerated long distances through the gray matter and reached the lower lumbar segments (L5) of the spinal cord. However, delayed OEC grafts failed to reduce posttraumatic astrogliosis. In conclusion, the beneficial effects found in the present study further support the use of OECs for treating chronic spinal cord injuries.

Animals↗
PubMed1985

Radionuclide methods of identifying patients who may require coronary artery bypass surgery.

Myocardial thallium-201 (201Tl) scintigraphy or radionuclide angiography performed in conjunction with exercise stress testing can provide clinically useful information regarding the functional significance of underlying coronary artery stenoses in patients with known or suspected coronary artery disease. Knowledge of type, location, and extent of myocardial 201Tl perfusion abnormalities or the severity of exercise-induced global and regional dysfunction has prognostic value. Risk stratification can be undertaken with either radionuclide technique by consideration of the magnitude of the ischemic response and may assist in the selection of patients for coronary artery bypass graft surgery (CABG). In patients with coronary artery disease, delayed 201Tl redistribution observed on exercise or dipyridamole 201Tl scintigraphy, particularly when present in multiple vascular regions and associated with increased lung 201Tl uptake, has been shown to be predictive of an adverse outcome, whereas patients with chest pain and a normal exercise 201Tl scintigram have a good prognosis with medical treatment. Similarly, a marked fall in the radionuclide ejection fraction from rest to exercise has been found to correlate with high-risk anatomic disease. In one published nonrandomized study, patients with coronary artery disease who demonstrated an abnormal ejection fraction response to exercise preoperatively had a better survival with CABG than with medical therapy. Another important application of radionuclide imaging in patients being considered for CABG (particularly those with a depressed resting left ventricular ejection fraction) is the determination of myocardial viability and potential for improved blood flow and enhanced regional function after revascularization. There are certain limitations of exercise 201Tl scintigraphy and radionuclide angiography that can be reduced by improved methods of quantitation of perfusion and function and further development of tomographic imaging approaches.

Coronary Artery Bypass↗
PubMed1996

Injury to hepatocytes and non-parenchymal cells during the preservation of human livers with UW or HTK solution: a determination of hepatocellular enzymes in the effluent perfusate for preoperative evaluation of the transplant quality.

In 50 livers harvested for transplantation, injury was assessed by determination of the enzymes in the effluent perfusate after cold ischemia. The results were compared to the histology and the clinical course after transplantation. Whereas the release of the markers of endothelial cell injury did neither correlate with the history of the graft nor with the postoperative course, the release of hepatocellular enzymes in the perfusate did indicate preexisting damage of the liver even when the biopsy showed normal liver tissue. Of 12 livers with high activity of hepatocellular enzymes in the effluent (activity of more than twice the median), 7 showed delayed onset of function or a primary non-function. In the other 38 livers with an enzyme activity below this borderline no delayed function or primary non-function was observed. Because of additional influences a prognosis of the function after transplantation was not possible, but the determination of the enzymes in the effluent of marginal livers probably allows the preoperative recognition of organs which will do well.

Adenosine↗
PubMed1997

Configuration of linear dynamic cardiomyoplasty for hypoplastic right ventricle.

BACKGROUND: The purpose of this study is to determine feasibility of linear dynamic cardiomyoplasty with a briefly preconditioned latissimus dorsi in the experimental model simulating patch enlargement of the hypoplastic right ventricle. METHODS: In 8 mongrel dogs, a diminished right ventricular chamber was reconstructed with an extended pericardial patch. A left latissimus dorsi, preconditioned for 2 weeks (2 Hz) after a previous 2-week vascular delay period, was placed on the patch, with the muscle fiber oriented in parallel to the right ventricular long axis. RESULTS: Graft pacing with trained-pulses of 25 Hz at a 1:1 ratio showed significant augmentation of pulmonary flow and pressure (158% +/- 21%, 156% +/- 14%, respectively), contributing to restoring right ventricular function comparable with preoperative control, which was also confirmed by the right ventricular function curve and pressure-volume relationship analyzes. Continuous pacing was performed in 4 animals for 7 hours without evidence of muscle fatigue, implying feasibility of "working conditioning" after minimum preconditioning for this type of right heart assist. CONCLUSIONS: Linear latissimus dorsi myoplasty can restore normal right ventricular performance at a physiologic preload, and may provide a surgical option for the hypoplastic right ventricle.

Animals↗
PubMed1983

Graft pretreatment with cyclosporin A. Long-term study including four trials in one and a half years.

Four trials were conducted to establish whether Cyclosporin A (Cy A) could be used as a graft pretreatment to prolong the graft function and animal survival of kidneys transplanted into bilaterally nephrectomized mongrel dogs. The first nonrandomized trial analyzed various parameters such as concentration, flush temperatures, effect of reflushing, and the need for subsequent minimal immunosuppression. By analyzing data from the ten groups in this trial, we established that 50 mg/l Cy A could be flushed successfully at either 4 C or 25 C without nephrotoxic effects. This concentration was found to prolong graft function and animal survival in some animals greater than 100 days. Reflushing the kidney after primary graft pretreatment with Cy A did not entirely remove the immunosuppressive effect of the drug as significant prolongation of survival also was observed in this group. In addition, minimal immunosuppression with azathioprine was necessary to observe a delay in the onset of rejection and prolongation of animal survival when Cy A was used for graft pretreatment. Trials 2 and 4 compared the efficacy of the original batch that was obtained later. The effects observed in Trial 1 and reproduced in Trial 3, which were randomized and double blinded using the original batch, were not seen in either Trials 2 or 4. This may have been related to the amount of time that the Cy A was dissolved in ethanol prior to its use or the batch of Cy A utilized. These preliminary results indicate that Cy A, when used for graft pretreatment under certain conditions, can delay the onset of rejection and prolong animal survival of transplanted renal allograft recipients.

Animals↗