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PubMed1997

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: functional analyses of lymphocytes and correlation with immunophenotypic recovery following transplantation.

Reconstitution of the immune system following T-cell-depleted bone marrow transplantation (BMT) in children has yet to be fully elucidated. Thus, we prospectively studied the recovery of immune function in 64 children who underwent T-lymphocyte-depleted marrow transplants using either matched family member donors or matched unrelated donors. We measured in vitro posttransplantation proliferative responses to phytohemagglutinin (PHA), concanavalin A, pokeweed mitogen, and Candida albicans antigen and assessed unidirectional allogeneic mixed-lymphocyte culture (MLC) responses at various times. A total of 129 healthy individuals served as normal controls for these assays. Responses to T-cell mitogens normalized within 12 months posttransplantation, while MLC responses normalized by 9 months. The presence of graft-versus-host disease (grade II or greater) and cytomegalovirus infection was associated with delays in immune function recovery. Importantly, immune function recovery correlated temporally with a rise in peripheral lymphocyte count. In contrast, the CD4/CD8 ratio was not predictive of immune recovery. Knowledge of immune function recovery may guide clinicians in devising strategies to minimize the risk of infection post-BMT.

Adolescent↗
PubMed1997

Early and delayed repair of orbitozygomatic complex fractures.

PURPOSE: The goal of this study was to review experience with early and delayed repair of orbitozygomatic complex fractures and develop guidelines for repair based on timing and extent of injury. PATIENTS AND METHODS: Records of patients with orbitozygomatic complex fractures over a 10-year period were reviewed for cause of injury, signs and symptoms, length of time from injury to repair, and method of repair. Results were evaluated by office examination and telephone interviews at least 6 months to 10 years after surgery. RESULTS: Seventy-eight patients who had undergone 81 surgical procedures were analyzed. The series consisted of 49 primary repairs (1 to 22 days postinjury), 10 delayed repairs using osteotomies at 21 days to 5 months postinjury, and 22 delayed repairs requiring onlay bone grafting from 4 months to 16 years postinjury. Forty patients (43 procedures) were available for follow-up. Early surgical intervention dramatically improved esthetic and functional outcomes, whereas late repair was less satisfactory. Hypoesthesia was not improved by surgery. Osteotomy and onlay grafting techniques were necessary for delayed treatment. CONCLUSION: Orbitozygomatic fractures can be repaired up to 21 days postinjury using primary reduction and fixation techniques. Osteotomies are required after 21 days and can be used successfully up to 4 months postinjury. After 4 months, successful repair requires onlay bone grafting.

Adolescent↗
PubMed1997

Mechanism of concordant corneal xenograft rejection in mice: synergistic effects of anti-leukocyte function-associated antigen-1 monoclonal antibody and FK506.

BACKGROUND: The mechanisms of corneal xenogeneic immunoreaction, as well as the potential role of immunosuppressive therapy in the suppression of corneal xenograft rejection, have not been thoroughly explored. METHODS: BALB/c mice who received orthotopic corneal transplants (Lewis rats donors) were administered intraperitoneally anti-leukocyte function associated antigen-1 (LFA-1) monoclonal antibody (mAb) or FK506 (3 mg/kg/day) or both of these immunosuppressants during a 12-day postoperative period. Histological (hematoxylin-eosin stain) and immunohistochemical evaluations of enucleated eyes were performed. Humoral immune response and delayed-type hypersensitivity (ear-swelling assay) were evaluated. RESULTS: The mean (+/-SD) graft survival time in the untreated control, FK506-treated, anti-LFA-1 mAb-treated, and combined-treatment groups was 5.8+/-0.8, 9.4+/-4.0, 8.7+/-5.0, and 67.7+/-16.4 days, respectively. In the untreated control group, mouse IgG, IgM, and C3 were expressed on the rat corneal grafts during the early postoperative phase. Flow cytometry studies revealed high titers of xenoreactive IgG and IgM antibodies. T helper 1 cytokines were expressed on xenografted corneal beds, and delayed-type hypersensitivity was induced. However, local expression of IgM, C3 and T helper 1 cytokines, serum antibodies of IgG and IgM, and delayed-type hypersensitivity were suppressed in the anti-LFA-1 mAb- plus FK506-treated group. CONCLUSIONS: Both humoral and cell-mediated immune reaction play an important role in the initial rejection in rat-to-mouse corneal xenotransplantation. The treatment with anti-LFA-1 mAb in combination with FK506 synergistically suppresses concordant corneal xenogeneic reaction.

Animals↗
PubMed2001

Immune reconstitution following hematopoietic stem-cell transplantation.

BACKGROUND: Reconstitution of the immune system following allogeneic stem-cell transplantation is a complex process that requires successful engraftment of the hematopoietic stem cell, as well as adequate thymic function. As the majority of patients have reduced thymic function due to age, hormonal changes, as well as the damage caused by conditioning and GvHD, immune recovery is often delayed and incomplete. Following graft infusion there is rapid proliferation of natural killer (NK) cells that appear to proceed directly from the hematopoietic stem cell. B-cell function is dependent on specific maturation development in the BM micro-environment, as well as CD4 help. The CD8 population expands rapidly due to proliferation of many memory cells that react against Class I Ags, as well as viral molecules. Expansion of T-helper cells originates mainly from the memory pool that is present in the bone marrow graft. Naive cells require competent thymus hence the CD4 cell counts may be subnormal with clinical immunodeficiency. Controversy remains as to the capacity of the thymus to recover and thus extra thymic proliferation of T cells have been postulated. However these cells appear to have a limited capacity to expand and a fixed repertoire. DISCUSSION: Donor lymphocyte infusions may contribute a competent CD4 population that can cause GvHD, but have limitations in the capacity to respond to new antigens. Future research needs to be concentrated on improving the capacity of the thymus to reconstitute a functional naive population.

Animals↗
PubMed1998

Cellular requirements of suprachiasmatic nucleus transplants for restoration of circadian rhythm.

Fetal neurografts containing the suprachiasmatic nucleus (SCN) can restore the circadian locomotor and drinking rhythm of SCN-lesioned (SCNX) rat and hamster. This functional outcome finally proves that the endogenous biological clock autonomously resides in the SCN. Observations on the cellular requirements of the "new" SCN for restoration of the arrhythmic SCNX animals have led to some new insights and confirmed findings from other studies. A critical mass of SCN neurons appeared necessary for functional effects, whereas the temporal profile of reinstatement of rhythm correlated with the delayed maturation of the grafted SCN. Cytoarchitectonically, the grafted SCN does not seem to develop normally for all anatomical aspects. Complementary clusters of vasoactive intestinal polypeptide(VIP)- and vasopressin(VP)ergic neurons are formed, but somatostatin(SOM)ergic neurons do not always "join" this group, as is normally seen in situ. Nevertheless, these new SCNs can restore the ablated functions. As the period length of restored rhythms tends to vary, it might be that the grafted SCN underwent an altered or impaired maturation that resulted in a different setting of its clock mechanism. A prominent role of VIPergic neurons seems indicated by their presence in all functional grafts, but, although they may be required, these cells do not appear to be a sufficient condition for restoration of rhythm. Many grafts exhibit the presence of VIPergic cells without counteracting the arrhythmia, whereas VP- and SOMergic SCN neurons are usually present as well. Findings with VP-deficient Brattleboro rat grafts indicated that VP is not the primary obligatory signal of circadian activity. It is argued that perhaps the role of SOMergic neurons in the clock function of the (grafted) SCN has been insufficiently considered. However, one should keep in mind that the peptides of the various types of SCN neurons may function only as cofactors, mutually modulating molecular or bioelectrical cellular activities within the nucleus or the message of the main transmitter gamma-aminobutyric acid.

Animals↗
PubMed2004

Hand-assisted retroperitoneoscopic nephrectomy for living kidney transplantation: initial 44 cases.

OBJECTIVES: To report our technique and early results of hand-assisted retroperitoneoscopic nephrectomy (HARN) for living donor transplantation and to assess its feasibility. METHODS: HARN was effectively and safely performed on 44 donors from July 2001 to September 2003 at Akita University Medical Center. We describe our techniques and experiences with HARN and compare the early results with those of 27 cases of open donor nephrectomy at our institution. RESULTS: The mean operating time was 260 minutes (range 173 to 445), the mean estimated blood loss was 249 mL (range 15 to 967), and the mean warm ischemia time was 2.2 minutes (range 0.8 to 6.4). These parameters were similar to those of open donor nephrectomy. Intraoperative and postoperative complications occurred in 1 (2.3%) and 2 (4.6%) cases, respectively, but they were all minor. HARN was converted to open nephrectomy in 1 case (2.3%) because of uncontrollable bleeding. All HARN donors were ambulant within 2 days postoperatively and could initiate oral intake on the first postoperative day. Regarding graft function, 41 recipients (93.2%) had an immediate onset of diuresis and 3 (6.8%) had delayed renal function. The serum creatinine 7 days and 1 month postoperatively was not significantly different between the HARN group and the open nephrectomy group. CONCLUSIONS: HARN for living donors is one excellent option for donor nephrectomy because the procedure does not require intraperitoneal manipulation, thus reducing the risk of abdominal visceral injury, and also because of the minimal warm ischemia time owing to rapid extraction of the kidney with hand assistance.

Adult↗
PubMed2003

Reverse anterior tibial artery flap for reconstruction of foot donor site.

The foot offers numerous useful options for hand reconstruction. Hallux transfer, dorsalis pedis flap, second toe transfers, and toe joint transfers offer good functional results in reconstructed hands. However, when the donor site is repaired with skin grafts, delayed wound healing, scarring, and contractures often result. Poor cosmesis of the donor site and altered gait are the main drawbacks of the procedures. The authors propose a new concept of primary reconstruction of the donor foot using a reverse-flow anterior tibial flap from the same leg. Two flaps are raised from the same anterior tibial vessel system in continuity as a distal free flap for hand reconstruction and as a proximal reverse-flow pedicled flap to resurface the donor defect. This technique allows good flap reconstruction of the foot donor site, reducing morbidity and limiting the operation to the same limb. The authors report their experience of 33 cases. There were no failures. Primary wound healing was achieved in the foot donor site, with acceptable cosmesis and satisfactory function.

Adult↗
PubMedDate not supplied

[Immune response of CBA mice in postnatal ontogeny].

Changes in the pattern of immune response of the CBA mice during postnatal ontogenesis were studied on the models of cellular and humoral immunity. The functions mediated by the amplifier cells were shown to undergo the most significant changes. This was confirmed by a decrease in the activity of antigen-nonspecific T-suppressors, as estimated in a semisyngeneic system, an increase in the capacity of spleen lymphoid cells to induce the "graft versus host" reaction with the age and preservation of the function of hypersensitivity effectors of delayed type at the same level (after the age of 3-4 months). It is suggested that these changes might cause an age decrease in the suppressor activity of T-cells in a response to insoluble antigens.

Aging↗
PubMed2005

Augmentation of post transplant immunity: antigen encounter at the time of hematopoietic stem cell transplantation enhances antigen-specific donor T-cell responses in the post transplant repertoire.

After transplant, the immune system is reconstituted by cells derived from both hematopoietic stem cells and peripheral expansion from differentiated donor T cells. After transplant, immune function is poor despite transplantation of mature lymphocytes from immune-competent donors. We tested the hypothesis that early antigen encounter at the time of cell transplant would improve the desired donor T-cell responses. Two independent models of peptide-specific T-cell responses were studied. The model for CD4 cells employed T cells from transgenic (Tg) DO11.11 mice that constitutively express the T-cell receptor for the class II-restricted ovalbumin peptide 323-339. The model for CD8 cells employed non-Tg H2-Db-restricted T-cell responses to the influenza nucleoprotein peptide 366-374. As measured both functionally and by direct imaging of T cells using clonotypic reagents, encounter with specific antigen at the time of T-cell transplantation led to clonal expansion of donor T cells and preservation of donor T-cell function in the post transplant immune environment. Antigen-specific donor T-cell function was poor if antigen encounter was delayed or omitted. Severe parent>F1 graft-versus-host reactions blocked the effect of early antigen exposure. Vaccination of transplant recipients against microbial or leukemia antigens may be worthy of study.

Animals↗
PubMedDate not supplied

[Delayed development of chimerism following T-cell depleted bone marrow transplantation].

Comparison of cytogenetic chimaerism was performed in two children after bone marrow transplantation (bmt) with resp. without T-cell depletion for ANLL. It showed a marked delay of full bone marrow function in the patient with a T-depleted graft. Host type bone marrow cells persisted over many months, whereas they disappeared quickly when undepleted marrow was transplanted. Donor-T-cells apparently interact with remaining host cells and thus they might more efficiently eliminate leukaemia. Therefore total removal of T-cells from the graft seems risky in bmt for leukaemia.

Bone Marrow Transplantation↗
PubMed2003

Kidney allograft and patient survival in type I diabetic recipients of cadaveric kidney alone versus simultaneous pancreas kidney transplants: a multivariate analysis of the UNOS database.

Simultaneous pancreas-kidney transplant (SPK) is now a common treatment for insulin-dependent diabetic patients with end-stage renal disease. Renal graft survival rates after SPK have been less well studied. This study compared the kidney survival results for 3642 SPK and 2374 cadaveric renal transplants (CRT) in type I diabetic patients at 112 US transplant centers reported to UNOS during 1994 through 1997. The analysis included follow-up information through September 2000. The kidney graft survival rates were significantly lower among recipients of CRT compared with SPK recipients (P < 0.001). Patients who received SPK were younger, less often sensitized, transplanted after shorter periods on dialysis, and less often black. The donors of SPK organs were younger, more often died from head trauma, were less often female, and more often black. SPK renal grafts were transplanted with a shorter cold ischemia time to more poorly HLA-matched recipients. After adjustment of these and other factors, whether a patient was recipient of CRT or SPK was not associated with increased risk of kidney graft failure or patient death. SPK recipients experienced half the rate of delayed kidney function (11% versus 23%) but nearly double the rate of rejections during the initial hospitalization (15% versus 9%) compared with CRT recipients. SPK was associated with better renal allograft survival compared with CRT, despite a higher rate of renal allograft rejection. This observation was explained by favorable donor and recipient factors in the SPK group. After controlling for these factors, SPK provided no protective or detrimental effect on short-term renal allograft or patient survival.

Adult↗
PubMed2002

The use of basiliximab in solid organ transplantation.

The risk of acute rejection is at its highest early post-transplant. The use of various antibodies early after transplant achieves potent immunosuppression to prevent acute rejection, allowing the clinician the opportunity to optimise baseline immunosuppressive management and to delay the use of nephrotoxic agents (calcineurin inhibitors), while the graft reaches a baseline function. Basiliximab (Simulect trade mark, Novartis) is a monoclonal antibody that binds specifically to the alpha-subunit of the human high-affinity interleukin-2 receptor (IL-2r) complex, consequently inhibiting interleukin-2 (IL-2) binding. IL-2 receptors are selectively expressed on the surface of the activated lymphocytes. Administration of basiliximab inhibits IL-2 mediated activation of lymphocytes, a critical pathway involved in allograft rejection. Several clinical studies have shown that basiliximab administration as an induction agent significantly reduces the incidence of acute rejection, even in high risk patients. In addition, basiliximab is well-tolerated with minimal side effects.

Antibodies, Monoclonal↗
PubMed1994

Hematogenous Salmonella typhi osteomyelitis of the radius. A case report.

Salmonella typhi osteomyelitis is an uncommon disease, usually associated with sickle cell anemia and other hemoglobinopathies, as well as with other disease states. In this case, Salmonella osteomyelitis was apparently caused by hematogenous spread after typhoid or enteric fever. After bone debridement, a segmental defect of the midradius resulted. Normal function was restored after radical debridement, intravenous antibiotics, and delayed tricortical iliac crest bone grafting of the segmental defect.

Adult↗
PubMed1991

A comparison of heterotopic and orthotopic intestinal transplantation in rats.

Two surgical techniques are commonly used for small intestinal transplantation: heterotopic (accessory) intestinal grafting (HIT), where the small bowel is initially defunctioned with restoration of intestinal continuity at a later date, and orthotopic (in continuity) intestinal grafting (OIT), where the small bowel is immediately anastomosed to the native intestine. The present experiments were undertaken to compare the advantages and disadvantages of these two surgical models. Graft barrier function (intestinal permeability), intestinal histology, and graft survival were evaluated after heterotopic and orthotopic intestinal transplantation in the following groups of rats: group 1: isografts, group 2: untreated allografts, group 3: low-dose cyclosporine-treated allografts (subcutaneous CsA 2 mg/kg/day), and group 4: high-dose CsA-treated allografts (subcutaneous CsA 4 mg/kg/day). Intestinal permeability was consistently higher after HIT than OIT in all of the groups (ANOVA; P less than 0.01). Histological evidence of rejection appeared earlier after HIT than OIT (HIT 5th postoperative day (POD); OIT 7th POD; P less than 0.05). The mean survival of untreated allografts was longer after HIT than OIT (HIT 15.7 +/- 6 days, OIT 9.2 +/- 1 days, P less than 0.05). The rats treated with low-dose CsA after OIT lost weight and died of rejection after a mean survival time of 17.7 +/- 2 days, while the rats treated with low-dose CsA after HIT remained well until sacrifice on POD 28 (P less than 0.01). The rats with isografts and rats with allografts treated with high-dose CsA remained well after HIT and OIT until sacrifice on the 28th POD. These data suggest that nutrients and other factors in the succus entericus may improve gut barrier function and delay the onset of rejection after OIT. However, rejection of the orthotopic intestinal graft is usually fatal, while rejection of the heterotopic graft is often surprisingly well tolerated. These factors must be taken into consideration when choosing a surgical technique for intestinal transplantation in humans.

Animals↗
PubMed1988

Arthrodesis of the proximal interphalangeal joint by solid bone grafting and plate fixation in extensive injuries to the dorsal aspect of the finger.

Eighteen patients with industrial injuries to the dorsum of the proximal interphalangeal joint involving articular destruction and segmental bone loss were treated by primary bone grafting and plating. Rigid arthrodesis and preservation of functional length were obtained in 25 fingers. Of the 25 fingers, 23 fused primarily. Because of technical error, one reconstruction showed delayed consolidation and required secondary grafting before uniting; one arthrodesis became infected and healed by second intention. Additional procedures were flexor tendon repair, nerve grafting, and local or distant flap coverage. The procedure is considered valid for the treatment of extensive skeletal damage to the proximal interphalangeal joint area.

Adolescent↗
PubMed1975

Prediction of kidney viability before transplantation.

A patient who receives a kidney transplant which fails suffers a physical and psychological disaster. Almost one-third of the kidneys transplanted in the United Kingdom are primary failures; many others function only after a delay, and the long term prognosis for these kidneys is poor. There is a need to identify kidneys which will function immediately after transplantation, those which will function after a delay and those which will never function. Such identification is seldom possible from the history. By continuous hypothermic perfusion we can identify a group of kidneys which will probably never function. The perfusate lactate level predicts which of the remaining kidneys will function immediately and which will not. Kidneys which function immediately after transplantation have a very much better long term prognosis after transplantation than those with delayed onset of function.

Cold Temperature↗
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↗