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PubMed2002

Restoration of upper extremity function after peripheral nerve injuries.

These days injuries to the peripheral nerves of the upper extremity that necessitate total or partial lesion are very common in the household and working environment. With regard to the majority of these injuries, not only plastic surgeons or neurosurgeons must have knowledge of their correct treatment, but general surgeons as well. The principles of reconstruction of the peripheral nerves of the upper extremity are described. The authors refer to immediate and delayed nerve repair, free nerve grafting, free vascularised nerve grafting, tendon transfer for a paralyzed hand, pedicled muscle transfer, functioning free muscle transplantation and neurotization.

Arm↗
PubMed1993

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression.

Acute Disease↗
PubMed1990

Critical mass of islets that function after implantation in a large mammalian.

A major problem that limits clinical islet transplantation is insufficient information on the critical quantity of islets needed to reverse insulin dependence. To address this problem, we have previously identified the critical number of purified islets of known size that consistently induced normoglycemia in a large mammal model of type I diabetes. In the present studies, we found that the dose-response relationship between the volume of islets transplanted and consistent normoglycemia in dogs corresponded to greater than 4.1 microliters islet tissue per kilogram body weight. The functional outcome of similar quantities of purified islets was then examined after autoimplantation into splenic or hepatic sites and after splenic implantation by venous reflux or pulp injection. During prolonged follow-up, four of five initially normoglycemic recipients of intrahepatic islets became hyperglycemic within 1 year and the other failed at 26 months. In contrast, function of intrasplenic islets was more durable with delayed onset of hyperglycemia observed in only two of six grafts at 13 and 18 months. Sustained normoglycemia was induced by splenic venous reflux of islets in six of seven dogs, but intrapulp injection succeeded in only two of six. Islet allografts implanted to the spleen (n = 10) or to the kidney capsule (n = 6) of Cyclosporine-treated recipients induced normoglycemia in all, but sustained function ensued in only the intrasplenic group when the islet mass was augmented by 40%. These data define the critical islet volume needed to induce normoglycemia in a large mammal. Islets implanted by venous reflux to spleen provide more durable long-term function than the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Cutaneous saphenous nerve graft for the treatment of sciatic neurotmesis in a dog.

CASE DESCRIPTION: A 2-year-old Griffon Vendéen was examined because of a 1-month history of right hind limb lameness after a traumatic injury. CLINICAL FINDINGS: Neurologic examination revealed monoplegia and anesthesia of the right hind limb distal to the stifle (femorotibial) joint except for the area supplied by the cutaneous saphenous nerve. Results of electromyographic testing were consistent with a severe lesion of the tibial and peroneal nerves at the level of the stifle joint. TREATMENT AND OUTCOME: Exploratory surgery revealed an 80-mm-long gap in both the peroneal and tibial branches of the right sciatic nerve. A section of the left cutaneous saphenous nerve was interposed to graft the nerve defects. The dog received joint mechanotherapy and electrophysiologic therapy during the reinnervation process. Ten months after surgery, the dog had recovered almost completely. Neurologic examination revealed diminished flexion of the tarsal and digital joints. Repeat electromyographic testing revealed no abnormal spontaneous electrical activity in the right hind limb musculature, and small compound muscle action potentials were recorded in the right interosseous and cranial tibial muscles. CLINICAL RELEVANCE: Without surgical treatment, neurotmesis injury results in poor recovery of motor and sensory functions and may result in amputation. If a nerve defect exists, nerve grafting should be considered, even if the procedure is delayed until well after the injury. The sensory portion of the cutaneous saphenous nerve is a potential source of peripheral nerve for grafting in dogs. Reinnervation is a long-term process and physiologic support and owner involvement are necessary, but nearly complete functional recovery is possible.

Animals↗
PubMed1998

Peripheral blood lymphoid subsets and long-term clinical course of kidney recipients: a longitudinal study.

A longitudinal study of peripheral blood lymphocyte subsets was performed in 23 renal allograft recipients treated with prophylactic antilymphocyte antibodies, CsA, and steroids. At day 0 samples were obtained before transplantation (Tx), and afterwards at months +1, +3, +6, +9, +12, +24, +36, and +48. In all patients, after the depletion of lymphoid subsets during antilymphocyte antibody treatment, CD8+ lymphocytes recovered and reached higher values than those observed prior to Tx. This was mainly due to an increase in CD8+CD45RA+ lymphocytes; in contrast, the levels of "memory" CD4+ T cells and the CD4+CD62L+ subset remained low during all the follow-up period. In patients with preserved graft function (n=14) (with creatinine levels below 200 micromol/mL), the initial, relative decrease in CD4+ T cells was never reversed and the recovery of CD8+ lymphocytes started early. They also presented a peak of HLA-DR antigen expression at 1 month, not observed in those patients displaying a suboptimal graft function. At 1 month, the patients with suboptimal graft function (n=9) (with creatinine levels above 200 micromol/mL) showed higher number of CD4+ T cells, delayed recovery of CD8+ lymphocytes, and higher percentage of activated lymphocytes from month +3 on than well-functioning kidney recipients. Both CD8+ lymphocytes and HLA-DR+ T cells, found at month + 1 post-Tx, were negatively correlated with the concentration of creatinine along the follow-up. Interestingly, the mean percentage of CD4+CD25+ T cells found 36 and 48 months after Tx were positively correlated with creatinine concentration at these times. These findings indicate that variations in the distribution of lymphocyte subsets are related with a long-term graft outcome. Within the first month after Tx, a rapid recovery of CD8+ lymphocytes, but not of CD4+ T cells, and a peak of HLA-DR expression, are associated with a good graft function. In contrast, long-term expression of activation markers is related with renal dysfunction.

Adult↗
PubMed1990

Late effects of total body irradiation and cytostatic preparative regimen for bone marrow transplantation in children with hematological malignancies.

Twenty-seven children, surviving disease-free for more than 1 year after allogeneic bone marrow transplantation (BMT) for hematological malignancy were evaluated for the long-term effects on endocrine function, sexual development, physical growth, appearance of ocular cataract and psychological sequelae. The growth rate was not decelerated in the prepubertal period in children not affected by chronic graft-versus-host (GVH) disease and without previous cranial irradiation. Development of sexual characteristics was delayed in 4 relevant cases. Thyroid function was not adversely affected, gonadal function was impaired in girls, transplanted after menarche, ocular cataract developed in all cases, irradiated without shielding of the eyes after 4 years. Psychologically, children after BMT had an advantageous social development.

Adolescent↗
PubMed2003

Outcome after reconstruction of the anterior cruciate ligament in athletic patients. A comparison of early versus delayed surgery.

We randomised 31 patients with acute tears of the anterior cruciate ligament (ACL) to receive either early (within 2 weeks) or delayed (8 to 12 weeks) reconstruction using a quadruple hamstring graft in order to determine if there was any functional advantage to early reconstruction. Outcome measures included return of knee movement, muscle dynamometry, International Knee Documentation Committee (IKDC) scores and Tegner activity levels. Two cases of symptomatic deep-venous thrombosis occurred in the early group. The mean range of movement was significantly greater at two weeks in the delayed group. Quadriceps muscle power was significantly better in the delayed group at 12 weeks (p < 0.05). These trends were evident at later time points, but were not statistically significant. One patient in each group had clinically significant knee stiffness at 52 weeks. IKDC scores and Tegner activity levels were not significantly different at 52 weeks. We conclude that there is no functional advantage to be gained by early reconstruction of the ACL.

Adolescent↗
PubMed1996

Impaired immune responses toward alloantigens and tumor cells but normal thymic selection in mice deficient in the beta2 integrin leukocyte function-associated antigen-1.

We have generated mice deficient in the beta2 integrin LFA-1 by targeted disruption of the CD11a gene in embryonic stem cells. In vitro LFA-1 -/- cells exhibit a delayed proliferative response toward alloantigens in the MLR. In vivo the host-vs-graft reaction toward injected allogeneic cells is also reduced. Alloantigen-specific CTLs generated from LFA-1 -/- mice are impaired in their cytotoxic activity toward allogeneic spleen cells as well as cell line targets. The proliferative response of LFA-1 -/- splenocytes following stimulation by LPS, PMA plus ionomycin, or immobilized anti-CD3epsilon mAb is normal, but Con A-stimulated proliferation is greatly diminished. We observe typical edema formation in a delayed type hypersensitivity reaction to SRBC with normal extravasation of leukocytes and demonstrate recruitment of neutrophils to an LPS-induced inflammatory site in these mice, suggesting that LFA-1 does not play an essential role in lymphocyte homing and leukocyte extravasation. We further show that LFA-1 -/- mice are susceptible to metastasis of B16 melanoma tumors, although their in vitro NK cell activity appears normal. A study of LFA-1 -/- mice expressing transgenic TCRs indicates that thymic maturation and selection of T cells are unaffected by the loss of LFA-1. Our results indicate that LFA-1 is important for alloantigen-triggered T cell proliferation and cytotoxicity, for Con A stimulation of T cells, and in tumor rejection. It does not appear to play an essential role in lymphocyte homing and leukocyte extravasation or in T cell maturation and selection in the thymus.

Animals↗
PubMed1988

Locally administered monoclonal antibodies to lymphocyte function-associated antigen 1 and to L3T4 prevent cutaneous graft-vs-host disease.

In vivo treatment with mAb directed against T cell surface molecules has been shown to prevent or reverse graft-vs-host disease (GVHD) and experimental autoimmune diseases, where T cells play a critical role. In this study we investigated the effects of in vivo administration of anti-I-A, anti-L3T4, and anti-lymphocyte function-associated Ag 1 (LFA-1) mAb on the development of murine cutaneous GVHD and delayed-type hypersensitivity responses evoked by local transfer of class II-MHC Ag-restricted, cloned autoreactive T cells. Prevention of cutaneous GVHD was achieved with local administration of either anti-L3T4 or anti-LFA-1 mAb, but not with anti-I-A mAb, while delayed-type hypersensitivity responses were inhibited by all the mAb. These results indicate that an I-A Ag-independent mechanism may be also operative in the development of the cutaneous GVHD, unlike the delayed-type hypersensitivity responses. Anti-LFA-1 mAb appeared to be more potent at inhibiting cutaneous GVHD rather than delayed-type hypersensitivity responses, whereas anti-L3T4 mAb inhibited equally both the responses. These results suggest that LFA-1 molecule may be involved in the epidermal invasion of T cells. Treatment with anti-LFA-1 mAb was found to be still, although less, effective at preventing cutaneous GVHD, even if the mAb was administered after the development of cutaneous GVHD.

Animals↗
PubMed1991

Ureteral obstruction after abdominal aortic surgery.

Obstructive uropathy following abdominal aortic surgery can no longer be considered a rarity. Early hydronephrosis, developing in the first postoperative year, occurs in 10% to 20% of patients; it usually runs a benign, self-limiting course. The incidence of delayed ureteral obstruction, which develops or persists after the first postoperative year, is unknown because it is asymptomatic in most cases. Although spontaneous resolution is possible, it seems that this late form is more likely to persist. The diagnosis of postoperative hydronephrosis is not an indication for urologic intervention. This should seldom be necessary; it should be reserved only for patients with evidence of worsening obstruction or deteriorating renal function. Early and particularly, delayed hydronephrosis seems to be a marker for present or impending graft complications, such as infection or false aneurysms. A prolonged follow-up is therefore mandatory whenever the diagnosis is established as it may improve long-term survival and limb salvage. The need for routine screening for this condition remains to be established. With the availability of noninvasive methods, such a task could be easily accomplished.

Aorta, Abdominal↗
PubMedDate not supplied

Greenstick fracture of the forearm with median nerve entrapment.

A case of bony median nerve entrapment is presented. Roentgenograms of a greenstick fracture without dislocation lured the examiner to ignore sensory deficit. Finally, delayed surgical exploration revealed complete nerve entrapment. A nerve graft was performed to reduce the functional loss.

Adolescent↗
PubMed1997

Does the granulocyte-macrophage colony-forming unit content in ex vivo-expanded grafts predict the recovery of the recipient leukocytes?

We have investigated the leukocyte-repopulating-predictive value of granulocyte-macrophage colony-forming unit (CFU-GM) analyses in ex vivo-expanded versus fresh murine bone marrow (BM) grafts. After the transplantation of graded numbers of normal BM cells (from 15 to 5 x 10(3) CFU-GMs/mice), a dose-dependent increase in the recipient leukocytes was observed between the first and third weeks posttransplantation. During these stages, increases in the graft size of 100-fold improved the leukocyte counts up to 30-fold and shortened the leukopenia period by 5 to 11 days, depending on the leukocyte threshold considered. To investigate whether similar correlations could be established using ex vivo-expanded samples, the size of the CFU-GM population was maximized by means of the preactivation of the BM with 5-fluorouracil (9-day 5FU-BM), followed by 3 days of incubation with interleukin-1 plus stem cell factor. Under these conditions, the CFU-GM content of the ex vivo-expanded grafts was 73-fold higher than that observed in equivalent femoral fractions of normal fresh BM. When equivalent fractions of both graft types were transplanted, an improved leukocyte recovery was observed in mice transfused with the expanded grafts. However, the leukocyte values obtained after the transplantation of the ex vivo-expanded samples were not as high as expected, based on the number of transplanted CFU-GMs. Analyses performed during the second week posttransplantation showed that, in comparison with normal fresh BM, ex vivo-expanded grafts containing 6 to 50 times more CFU-GMs were required to generate a similar number of leukocytes. These results were confirmed in both the peripheral blood leukocytes and the myeloid Gr1+ cells, when similar numbers of CFU-GMs were transfused in the fresh and the ex vivo-expanded BM. The possibility that the preactivation of the ex vivo-expanded grafts with 5FU had a role in this effect was ruled out, because the leukocyte repopulation capacity of fresh 5FU-treated BM was as high as that observed in normal fresh BM which contained a similar number of CFU-GMs. Neither by extending the ex vivo incubation period nor by using other hematopoietic growth factor combinations was the functional capacity of the expanded grafts improved. The results presented in this study are consistent with the belief that ex vivo expansion procedures will be a useful tool for improving the hematologic recovery of patients who receive hematopoietic transplants. However, our data indicate that predicting the leukocyte repopulating capacity of ex vivo-expanded grafts according to correlations established with numbers of fresh CFU-GMs can lead to overestimations of their function, and therefore to unexpected and delayed hematopoietic engraftments.

Animals↗
PubMed2000

Immune reconstitution: an important component of a successful allogeneic transplantation.

The recipients of allogeneic haematopoietic stem cell transplants are characterised by an immunodeficiency of varying severity and duration. Their immunocompromised state is due in part to: (1) an impaired recapitulation of lymphoid ontogeny, (2) a lack of sustained transfer of donor immunity, (3) the effects of graft versus host disease and its therapy, and (4) a reduction in thymic function. Recipients can have delays in the production of naive T lymphocytes following transplantation which result in defects in the production of new antigen specific T lymphocytes and an inability to produce antibodies, especially to carbohydrate antigens. T-cell proliferation as well as immunoglobulin production remains impaired usually until the second half of the first year post-transplant. Other factors that can influence immunological reconstitution include the donor-recipient relationship (histocompatible or matched unrelated donor), intervening infections and recipient age, among others.

Adult↗
PubMed1982

Cells mediating graft rejection in the mouse. IV. The Ly-5, 6, and 8 effector cell phenotype.

Skin graft rejection was previously shown to be mediated by sensitized lymphocytes bearing the Thy-1+, Ly-1+2-3- cell surface phenotype and these cells were further characterized using antisera to the Ly-5, 6, and 7 specificities. By using an adoptive transfer system in which ATXBM mice (CBA/H) received sensitized cells treated with antiserum and complement, it was shown that the cells mediating skin graft rejection were of the Ly-5+6-7+ phenotype. Other studies have demonstrated that cytotoxic T cells are Ly-5+6+7-, whereas helper T cells are Ly-5+6-7+, so that the T cells-mediating graft rejection is again clearly distinguished from the cytotoxic T. cell. At this time, however, it is not possible to separate the T cells mediating helper T cell functions, delayed-type hypersensitivity (DTH), and allograft rejections.

Animals↗
PubMed2005

alpha1,3-Galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months.

BACKGROUND: The recent generation of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs has allowed investigation of the survival of GalT-KO pig organs in nonhuman primates. METHODS: Heterotopic heart transplantation from GalT-KO pigs was carried out in baboons (n=8) using a human antihuman CD154 monoclonal antibody-based immunosuppressive regimen. RESULTS: In six of the eight cases, graft survival extended to between approximately 2 and 6 months. All grafts developed thrombotic microangiopathy (TM). In particular, the clinical course of one baboon in which the graft functioned for 179 days is summarized. This baboon received aspirin (40 mg on alternate days) from day 4 in addition to heparin, which may have been a factor in the delay of onset and progression of TM and in prolonged graft survival. Maintenance therapy with anti-CD154 mAb, mycophenolate mofetil, and methylprednisolone was associated with persistently low numbers of CD3CD4 and CD3CD8 cells. Despite persisting depletion of these cells, no infectious complications occurred. CONCLUSIONS: It remains to be established whether TM is related to a very low level of natural preformed or T-cell-induced antibody deposition on the graft, inducing endothelial activation and injury, or to molecular incompatibilities in the coagulation mechanisms between pig and baboon, or to both. However, function of a pig organ in a baboon for a period approaching six months, which has not been reported previously, lends encouragement that the barriers to xenotransplantation will eventually be overcome.

Animals↗
PubMed1980

Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allografts.

A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation.

Animals↗
PubMed1993

Is there an optimal time for the first cyclosporin dose in renal transplantation?

It is customary for patients undergoing kidney transplantation to receive their first dose of cyclosporin either just before or during the transplant operation. This ensures the early establishment of good levels of immunosuppression but might depress early graft function and contribute towards the development of acute tubular necrosis. In a controlled clinical trial, we have studied the effects of withholding cyclosporin for 12 h in patients undergoing cadaveric renal transplantation. Consecutive adult recipients of a cadaveric renal transplant were randomised to receive their first dose of cyclosporin (10 mg/kg p.o.) 6 h prior to transplant surgery or 12 h afterwards. All patients received azathioprine (1.5 mg/kg i.v.) and methylprednisolone (0.5 g i.v.) in addition during surgery. From the 2nd day onwards both groups were treated with an identical triple immunosuppressive regimen. The 27 patients who received their first dose of cyclosporin post-operatively had significantly better immediate and subsequent function than did the 26 patients who received their cyclosporin at the time of surgery. The delayed dosing was associated with improved graft survival and no increase in the frequency of rejection episodes. This regimen is recommended for all patients receiving triple therapy.

Adult↗
PubMed1998

Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after revascularization.

OBJECTIVES: We sought to define the effects of time on contractile function, morphology and functional recovery after coronary revascularization in patients with dysfunctional but viable (hibernating) myocardium. BACKGROUND: Functional recovery after coronary artery bypass graft surgery in patients with chronic myocardial hibernation is incomplete or delayed. The proposed cause is a progressive temporal degeneration of cardiomyocytes. METHODS: In 32 patients with multivessel coronary disease, regional wall motion analysis was performed in hypoperfused but metabolically active areas before and 6 months after bypass surgery. During bypass surgery, transmural biopsy samples were obtained from the center of the hypokinetic zone for light and electron microscopic analyses. The proposed duration of myocardial hibernation was retrospectively assessed. RESULTS: Patients with a subacute hibernating condition (<50 days) demonstrated a higher preoperative ejection fraction (EF, 50+/-8%), and a better preserved wall motion (WM) in the supraapical wall (-1.4+/-0.4) than did patients with intermediate-term (>50 days, EF 37+/-9%, p < 0.05; WM -2.4+/-1.5, p = 0.08) or chronic (>6 months, EF 40+/-14%, WM -2.7+/-0.9, p < 0.005) ischemia. Structural degeneration correlated with the duration of ischemia (r = 0.56, p < 0.05). Postoperative recovery of function was enhanced in patients with a short history of hibernation compared with patients with an intermediate-term or chronic condition (EF 60+/-10% vs. 40+/-10%, p < 0.001, and vs. 47+/-14%, p < 0.05). CONCLUSIONS: Hibernating myocardium exhibits time-dependent deterioration due to progressive structural degeneration with enhanced fibrosis. Early revascularization should be attempted to salvage the jeopardized tissue and improve postoperative outcome.

Aged↗