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PubMed1994

[Lesions of the renal pedicle in blunt abdominal trauma in children. 7 cases].

The frequency of urinary tract trauma in children is difficult to estimate. Renal pedicle lesions are estimated to represent 10% of all forms of urinary tract trauma. These lesions are difficult to diagnose and may be completely missed. Over a 12 year period, we have treated 7 children with a renal pedicle injury. Haematuria was immediate in 3 cases, delayed in 2 cases and absent in 2 cases. The diagnosis is based on intravenous urography or postcontrast computed tomography. Treatment consisted of disobstruction with intimal suture with a good result, but impaired renal function, an upper pole nephrectomy, functional aorto-renal bypass graft but with altered renal function, total nephrectomy and 3 cases of surveillance with one non-functioning kidney. None of these children are hypertensive. The authors discuss the diagnostic approach, the contribution of imaging and the therapeutic options and results.

Abdominal Injuries↗
PubMed1993

High mortality in systemic fungal infections following renal transplantation in third-world countries.

Amongst 310 recipients of live related renal transplants, systemic fungal infections were observed in 19 patients (6.1%). These included cryptococcosis in eight (42%), candidiasis in seven (37%), mucormycosis in two (11%), aspergillosis in one (5.5%), and a mixed cryptococcal and Aspergillus infection in one patient (5.5%). Infections occurred within 12 months of transplantation in seven patients and after 13-37 months in the remaining patients. Prolonged fever not responding to antibiotics was the most common presentation. Central nervous system was involved in all patients with cryptococcosis, while Candida infection primarily involved the urinary tract. Both patients with mucormycosis exhibited signs and symptoms of florid rhinocerebral disease and a rapid downhill course. Pulmonary manifestations were the most prominent features of patients with aspergillosis. Parenteral amphotericin B with or without 5-fluorocytosine was started in all, but three patients could receive the therapy only for 1-3 weeks. Three patients with cryptococcosis developed amphotericin-related complications and were changed to oral fluconazole. Seven patients recovered and 12 (63%) died. None of the patients had cytomegalovirus infection preceding the onset of fungal disease. The high frequency of fungal infections amongst our allograft recipients could not be ascribed to over immunosuppression, since 16 patients (84%) were only on maintenance doses of immunosuppressive drugs and in 13 (68.4%) graft function was normal at the time of diagnosis. The high frequency of fungal infections in our patients was most probably related to the poor hygienic and sanitary conditions which continue to be prevalent in the tropical environment of third-world countries. Delays in the diagnosis and late institution of therapy result in a high mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspergillosis↗
PubMed1996

Predictors of the response to growth hormone in short prepubertal children post-renal transplant. German Study Group for Growth Hormone Treatment in Children Post Renal Transplantation Study Group Members.

The growth response to recombinant human growth hormone (rhGH) in post-renal transplantation children is variable. We sought to determine predictive factors of this variable effect of rhGH by analysis of a homogeneous group of 16 prepubertal children with a median age of 12.4 years (range 7.7-18.0 years). rhGH was given at 30 i.u./m2/week for at least one year. All children remained prepubertal during the study period. Height velocity increased from 2.5 +/- 0.4cm/year to 7.4 +/- 0.5cm/year after one year of treatment (p < 0.001). The growth response to rhGH (height velocity after one year of rhGH) was not significantly correlated with the dose of prednisolone administered (range 2.3-9.1mg/m2/day), graft function as estimated by creatinine clearances (range 19-88ml/min/1.73m2), the degree of stunting at baseline, baseline height velocity, or chronological age. However, a relatively tight inverse correlation was found between the growth response to rhGH and the degree of bone age delay (r = 0.73, p < 0.005). Hence, the degree of bone age delay appears to be a helpful clinical predictor of response to rhGH in short prepubertal children post-renal transplantation.

Adolescent↗
PubMed2003

Angiogenic and neurotrophic effects of vascular endothelial growth factor (VEGF165): studies of grafted and cultured embryonic ventral mesencephalic cells.

The present series of experiments investigated the effects of vascular endothelial growth factor (VEGF165) on adult rat striatal cerebrovasculature and embryonic dopamine (DA) neuron allografts in a rat model of Parkinson's disease (PD). We examined VEGF165's ability to (1) alter the vascular network of the adult rat striatum, (2) influence the vascular growth of solid embryonic day 14 (E14) ventral mesencephalic (VM) grafts when placed into a VEGF-pretreated host striatum, (3) alter the function and survival of E14 VM grafts when transplanted into an adult DA-deleted striatum, and (4) influence cell survival and neurite growth in cultures of E14 VM cells. We demonstrate here that a single bolus injection of VEGF165 into the adult rat striatum significantly increases the amount of vasculature in the vicinity of the injection site in a delayed and transient manner when compared to saline controls. Transplanting solid E14 VM grafts into the VEGF165-pretreated striatum resulted in a homogeneous distribution of small blood vessels throughout the graft, a pattern that closely resembles mature adult vasculature. In contrast, grafts in the control condition contained a patchy distribution of heavily dilated vessels. Behavioral measurements indicate that VEGF pretreatment of the intrastriatal graft site accelerates recovery of amphetamine-induced rotational asymmetry in unilateral 6-OHDA lesioned rats. Unexpectedly, however, VEGF pretreatments failed to increase survival of tyrosine hydroxylase-immunoreactive (THir) neurons in the grafts. In contrast to this finding in vivo, adding VEGF165 to glial-reduced E14 rat VM cultures produced a fourfold increase in THir cell survival and a doubling in the length of THir neurites. We conclude that with the proper method of delivery, VEGF165 may prove to be one of several strategies necessary to significantly improve the survival and function of fetal VM tissue grafts.

Animals↗
PubMed1996

Renal allograft rupture: a clinical review.

Rupture of a renal allograft (RAR) is an uncommon but serious complication of renal transplantation. A recent RAR prompted a review of our experience, with the purpose of (1) identifying conditions that may predispose this complication and (2) defining strategies for prevention. A 5-yr, consecutive living-related (LRD) and cadaver donor (CD) cohort of 331 patients was studied retrospectively. Twelve patients (3.6%) had RAR. Donor characteristics, procurement and preservation conditions, and recipient characteristics were major study categories. Data analysis was computer-based and included multivariate analysis. The nine White and two Black cadaver donors were "ideal", mean age 29 yr, with mean high creatinine (CR) of 1.3 and terminal CR of 1.1 mg/dl and mean terminal urine output of 423 ml/min. Nine of 11 CD had low-dose dopamine use (terminal, mean 8, range 5-13 micrograms/kg/min). Eleven of 11 donors had procurement en-bloc, 9 of which were multiple organ procurement. All had 4+/4+ flush and cold storage with UW solution. Mean cold ischemia time (CIT) was 22 h, 28 min (range 15 h, 16 min to 40 h). For patients with RAR mean age was 39 yr; there were 12 Black patients and 7 males, 5 females. HLA match was 1 antigen (AG) for 3, 2 AG for 8, and 4 AG for 1 (mean 1.9). Nine patients had delayed or declining renal function requiring dialysis. The panel reactive antibody was at peak, mean 47% (range 0-100%) and current, mean 18% (range 0-84%). Six of 12 had OKT3 therapy at time of RAR and six had biopsies. Day of RAR was mean 10, median 9 (range 4-21). Pain and drop in hematocrit were observed in most. There was one fatality (8%), and all kidneys were removed. All kidneys showed at least minimal rejection but six had severe acute tubular necrosis (ATN) with edema and minimal rejection. Statistically significant associations with RAR were older recipient age (p = 0.01), donor-recipient race mismatch (White donor to Black recipient) (p = 0.007), and dialysis requirement (p < 0.001). Other variables were not statistically correlated: gender, race, CIT, transplant number, LRD vs. CD, peak or current PRA, and total HLA and BDR mismatch. The data suggest that ATN and rejection act synergistically to cause RAR and that early delayed function requires intensive and perhaps novel immunosuppression, especially in Black recipients.

Adolescent↗
PubMed1977

Effects of trypan blue treatment on the immune responses of mice.

It has been reported that trypan blue treatment decreases the nonspecific resistance of mice to transplanted tumors and inhibits the in vitro cytotoxic activity of activated macrophages. We wished to determine whether this effect of trypan blue could be due to a selective inhibition of certain macrophage functions or whether it reflected a broader form of immunosuppression. We therefore tested the effects of trypan blue on a variety of immunological responses. Treatment of mice with trypan blue delayed their rejection of skin allografts and transplants of a highly antigenic syngeneic ultraviolet light-induced tumor. Trypan blue treatment of either donor or recipient decreased the local graft-versus-host reaction. Filtration of lymph node cells from trypan blue-treated donors on a nylon wool column before use in the graft-versus-host assay abrogated the depressive effect of trypan blue. A transient reduction in the blastogenic response of spleen cells to concanavalin A and lipopolysaccharide mitogens was observed after a single injection of trypan blue, but the response of lymph node cells was unaffected. The depressed response of splenic lymphocytes was not entirely reversed by removal of adherent cells. The primary and secondary hemagglutinin responses to sheep erythrocytes were unaffected in trypan blue-treated mice, and the proportion and phagocytic activity of thioglycolate-induced peritoneal macrophages were also unaltered. We conclude that treatment of mice with trypan blue selectively inhibits certain macrophage functions but, at high doses, it can also inhibit some lymphocyte activities.

Agglutinins↗
PubMed2000

Repair of nerve gap with the elongation of Wallerian degenerated nerve by tissue expansion.

We have found previously that expansion of the Wallerian degenerated nerve was accompanied by accelerated Schwann cell proliferation. In this study, we investigated the usefulness of the elongation of Wallerian degenerated nerve for the repair of short nerve gap. Male Wistar rats were used. After the left sciatic nerve was transected the rats were divided into 4 groups. In the control group, nerve coaptation was not performed. In group 1, tensionless coaptation was performed immediately. In group 2, delayed tensionless coaptation was performed with the elongation of Wallerian degenerated nerve. In group 3, coaptation was performed immediately with autologous interposition nerve graft. The ideal tensionless nerve repair of group 1 was considered to produce the best result. Rats in group 2 showed functional recovery as good as rats in group 1. On histologic assessment, in group 2, a fibrous capsule that was very rich in vascularity was formed around the tissue expander. After 14 weeks, the capsule was diminished markedly in size, but the vascularity was rich around the sciatic nerve. We think that the excellent functional recovery seen in group 2 can be attributed to the increased activity of Schwann cell proliferation and increased vascularity.

Animals↗
PubMedDate not supplied

Lateral humeral condylar fractures in children.

Fifty-three patients with 56 fractures of the lateral humeral condyle were reviewed and the results were assessed to determine the amount of displacement that could be relied on to produce satisfactory results. Closed treatment resulted in satisfactory results if the initial displacement did not exceed 2 mm. This required close follow-up for detection of displacement. Percutaneous pinning of nondisplaced and minimally displaced fractures is an acceptable alternative in any situation in which close scrutiny cannot be ensured. Those fractures with greater than 2 mm of displacement should be reduced, pinned, and immobilized for 6-8 weeks. Evidence of delayed union after 8 weeks is an indication for internal fixation and possibly bone grafting. Established nonunions in good position are best treated by open reduction and bone grafting. In this series, varus deformity was the most common deviation from a normal carrying angle. The functional results were invariably good regardless of the radiographic or clinical findings.

Adolescent↗
PubMed1980

Secondary intention healing as an adjunct to the reconstruction of mid-facial defects.

Facial skin cancer has a high incidence during later life. The majority of our patients had been previously treated by a number of different modalities. The recurrence of persistance of their cutaneous neoplasm was often quite extensive and thus required a rather large excision to eradicate the disease. Employment of a number of small operations under local anesthesia in which the patients could return to their home environment provided for a potential reduction in psychological and physical morbidity. The use of delayed healing often allowed reconstruction with a local flap or skin graft that if reconstructed primarily would have necessitated a more extensive operative procedure. Use of local flaps and/or skin grafts avoided excessive blood loss and long periods of immobilization associated with larger regional and distant flaps. Finally the denial of reconstructive surgery because of age should be condemned since fairly small operations in conjunction with delayed wound healing can provide acceptable cosmetic and functional results.

Aged↗
PubMed2002

Allogeneic reconstitution after nonmyeloablative conditioning: mitigation of graft-versus-host and host-versus-graft reactivity by anti-CD44v6.

T-cell maturation is accelerated in transgenic mice expressing rat CD44v4-v7 on T cells, the effect being blocked by anti-CD44v6. This finding suggested functional activity of CD44v6 in thymocyte development. We tested the hypothesis by antibody blocking and using mice with targeted deletion of CD44v6/v7 exon products (CD44v6/v7(-/-)). When lethally irradiated CD44v6/v7-competent (CD44v6/v7(+/+)) mice were reconstituted syngeneically, higher numbers of CD44v6/v7(-/-) than CD44v6/v7(+/+) BMC were required for survival, the period of reconstitution was prolonged, and regain of immunocompetence was delayed. Similar findings were observed in lethally irradiated, anti-CD44v6-treated syngeneic CD44v6/v7(+/+) hosts. Thus, CD44v6/v7 supports maturation and expansion of hematopoietic progenitor cells. Surprisingly, reconstitution with CD44v6/v7(-/-) BMC or anti-CD44v6 treatment of the nonlethally irradiated allogeneic CD44v6/v7(+/+) host had only a minor impact on survival rates. When nonlethally irradiated CD44v6/v7(-/-) hosts received an allogeneic graft, survival rates were improved. These phenomena have been a result of reduced GvH reactivities when the donor was CD44v6/v7(-/-) and reduced HvG reactivities in the CD44v6/v7(-/-) host. Thus, although a deficit or blockade of CD44v6/v7 has a negative impact on hematopoietic reconstitution, a transient blockade will be of benefit for the allogeneically reconstituted host because of a strong reduction in GvH and HvG reactivities.

Animals↗
PubMed1981

Assessment of environmental contaminant-induced lymphocyte dysfunction.

Although it has been established that environmental contaminants can alter immune function, the mechanisms of action have yet to be determined. This paper reviews the effects of hydrocarbon environmental contaminants on lymphocyte function and presents an approach which may serve to delineate the mechanisms of action. The approach is based on the use of the developmental phases of an immune response and assays which can be used for their functional assessment. Possible interactions between environmental contaminants and lymphocyte function and factors which must be considered in the evaluation of immune status are discussed. In addition, a study on the influence of the chronic exposure to two polyhalogenated hydrocarbons, PCB and HCB, on several parameters of lymphocyte function in mice is presented.

Animals↗
PubMed1991

Single center experience of the effect of delayed function on outcome in retransplant recipients of cadaveric renal allografts.

The incidence of DRF in the regraft study group was most commonly seen in patients with a historic high level of HLA sensitization. Primary NF was an immune mediated event seen in 63% of third regrafts. Delayed use of CyA with ALG induction coverage provides good graft survival with either double or triple maintenance therapy. Stricter patient selection for third transplants and aggressive clinical monitoring of the regrafted patient has provided a 1-year actuarial graft survival result of 88% at our transplant center.

Antilymphocyte Serum↗
PubMed2002

Draining lymph nodes play an essential role in alloimmunity generated in response to high-risk corneal transplantation.

PURPOSE: To further evaluate the role of draining cervical lymph nodes (CLN) in high-risk (HR) corneal allografts performed in vascularized beds. Recently, we have shown that CLN are critical for promotion of allograft rejection in normal-risk corneal allografts. METHODS: Fully mismatched HR orthotopic corneal transplantation was performed in BALB/c hosts that had their CLN excised before transplantation (CLN-). Graft rejection and allospecific delayed-type hypersensitivity (DTH) were used as measures of alloreactivity. Numbers of interferon gamma (IFN-gamma)- and interleukin 2 (IL-2)-expressing cells were compared among hosts that retained their native CLN (CLN+) and CLN-hosts. Additionally, splenectomized mice (Sp-), and hosts without either CLN or spleen (CLN-Sp-) were evaluated. RESULTS: Within 5 weeks, 100% of HR grafts among CLN+ hosts were rejected, and hosts of these grafts uniformly demonstrated allospecific delayed-type hypersensitivity (DTH). In contrast, 92% of CLN-hosts accepted their HR allografts, and demonstrated suppressed allospecific DTH response. Moreover, significantly lower numbers of IFN-gamma- and IL-2-expressing cells were infiltrating corneal grafts in CLN-group. All Sp-hosts rejected corneal allografts in an accelerated manner, whereas 86% of CLN-Sp-hosts accepted their allografts indefinitely. CONCLUSIONS: Draining CLN play a critical role in alloimmunity and rejection of HR corneal grafts, suggesting the essential function of CLN in corneal alloimmunization regardless of the degree of preoperative risk. Modulation of factors that regulate access of alloantigens or antigen-laden antigen-presenting cells to draining CLN may offer novel strategies in controlling induction of alloimmunity in corneal transplantation.

Animals↗
PubMed1998

Down-modulation of host reactivity by anti-CD44 in skin transplantation.

BACKGROUND: A major goal in transplantation medicine is to achieve donor-specific tolerance while sustaining unaltered immunoreactivity toward donor-independent stimuli. Pretransplant immunization and concomitant blockade of costimulatory molecules may be one way to achieve this goal. We investigated whether transplant acceptance could be achieved by sensitization with semiallogeneic blood and blockade of CD44s (standard isoform) or CD44v6 (variant exon 6), since the adhesion molecule CD44 is known to function as a costimulatory molecule in T-cell activation. METHODS: Immunoregulatory regimens were examined in BDX rats that had received full-thickness (DA x BDX)F1 skin grafts by controlling graft acceptance and immunoreactivity. RESULTS: When BDX rats received full-thickness (DA x BDX)F1 skin grafts together with either anti-CD44s or anti-CD44v6, graft rejection was delayed, but none of the animals accepted the graft. An analysis of immunoreactivity revealed reduced numbers of infiltrating lymphocytes in anti-CD44s- as well as anti-CD44v6-treated rats. Expansion of donor-specific helper and cytotoxic T cells was particularly impaired in anti-CD44v6-treated rats. The effect of anti-CD44s could not be intensified by presensitization with donor-derived blood. However, when rats received anti-CD44v6 concomitantly with presensitization, 75% permanently accepted the graft and 50% accepted a second graft provided they were continuously treated with anti-CD44v6 and received a low dose of cyclosporine (CsA) during the first weeks after grafting. The frequency of graft-reactive helper T cells was reduced to less than 10% of the level in controls, and cytotoxic T cells could hardly be detected. CONCLUSION: According to the in vivo and the vitro analyses of the graft and the draining lymph nodes, anti-CD44s blocked homing of activated lymphocytes into the graft, while anti-CD44v6 inhibited clonal expansion of donor-specific T cells. Suppression by anti-CD44v6 apparently functioned distinctly to cyclosporine and was most effective in combination with presensitization. Since expression of CD44v6 on lymphocytes is restricted to a short period during lymphocyte activation, anti-CD44v6 treatment could lead to a quite specific immunosuppression during a limited time period.

Animals↗
PubMed2003

Infectious complications after allogeneic stem cell transplantation: epidemiology and interventional therapy strategies--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

The risk of infection after allogeneic stem cell transplantation is determined by the underlying disease, the intensity of previous treatments and complications that may have occurred during that time, but above all, the risk of infection is determined by the selected transplantation modality (e.g. HLA-match between the stem cell donor and recipient, T cell depletion of the graft, and others). In comparison with patients treated with high-dose chemotherapy and autologous stem cell transplantation, patients undergoing allogeneic stem cell transplantation are at a much higher risk of infection even after hematopoietic reconstitution, due to the delayed recovery of T and B cell functions. The rate at which immune function recovers after hematopoietic reconstitution greatly influences the incidence and type of post-transplant infectious complications. Infection-associated mortality, for example, is significantly higher following engraftment than during the short neutropenic period that immediately follows transplantation.

Humans↗
PubMed1986

T-cell independent transfer of organized granuloma formation.

A direct role for delayed hypersensitivity in organized granuloma formation has been emphasized in the literature, but some clinical and experimental studies have suggested a more complicated relationship. In order to further evaluate T-cell function in cutaneous granulomatous inflammation, hepatic granulomas isolated from athymic mice with schistosomiasis were grafted into the skin of athymic and euthymic mice. Granulomas developed in athymic mice, as seen previously after transplantation of euthymic hepatic granulomas, indicating that granulomas develop in the skin without T-cell function. However, the granulomas in athymic mice skin were smaller and lacked eosinophils and mast cells, whereas the athymic mouse granulomas grafted in euthymic mice skin were larger, better organized, and associated with tissue eosinophilia. These findings suggest that granuloma initiation itself is T-cell independent, but that T-cell participation enhances the granulomatous reaction.

Animals↗
PubMed1989

Bone marrow transplantation for severe aplastic anaemia using cyclosporin: long-term follow-up.

Between 1980 and 1986 we transplanted 49 patients from genotypically identical sibling donors for severe aplastic anaemia (SAA). Patients were predominantly adults, median age 22 years (3-47). Forty-six were multiply transfused prior to referral. The median pre-transplant disease duration was 4 months (1-72). Pre-transplant conditioning was with cyclophosphamide (CY) 200 mg/kg. Cyclosporin A (CSA) was given from 1 day before the transplant and continued for 9-12 months. Eight of 48 evaluable patients did not achieve initial engraftment (early graft failure). Six of these episodes occurred in the eight cases transplanted more than 1 year after diagnosis, four of whom died. Thirteen of 44 (30%) evaluable patients (with stable engraftment after one or two transplants) had grade III-IV acute graft-versus-host disease (GVHD). Only three of 35 patients surviving more than 100 days with sustained engraftment developed generalized chronic GVHD; two died. An additional 10 patients developed localized chronic GVHD, which was very mild, transient and related to CSA withdrawal. Four long-term survivors are known to have autologous marrow function. All survivors have Karnofsky scores of greater than 90%. We conclude that the use of CSA after bone marrow transplantation for SAA is associated with good long-term survival and minimal on-going chronic GVHD. Early graft failure was frequent when transplantation was delayed beyond 1 year from diagnosis.

Anemia, Aplastic↗
PubMed1989

Functions of vascular wall cells related to development of transplantation-associated coronary arteriosclerosis.

The accelerated form of arteriosclerosis that occurs in the coronary circulation of transplanted hearts currently presents a major limitation to the long-term success of this therapy. The pathogenesis of this lesion is unclear. Recent advances in vessel wall biology have disclosed interplay between mediators of the immune response and functions of vascular cells of potential significance in the formation of this accelerated form of arterial disease. We hypothesize that the development of accelerated arteriosclerosis in the arteries of transplanted hearts represents a form of chronic immunologic reaction resembling delayed-type hypersensitivity localized in the graft's arteries, a manifestation of cellular immunity mediated in large part by a regionally acting cytokine network. We emphasize the active responses of intrinsic vessel wall cells, including inappropriate expression of HLA and the likely participation of cytokines derived from vascular cells as well as from infiltrating leukocytes in amplification and propagation of this localized chronic immune reaction. This mechanism, which involves helper T cells interacting with class II HLA, may distinguish transplantation-associated arteriosclerosis from typical acute rejection, which may involve primarily cytolytic T cells interacting with class I HLA. Lesions of the common variety of atherosclerosis manifest certain features of immune activation. Therefore, we further hypothesize that the transplantation-associated form represents an extreme case of processes that also contribute to usual coronary atherosclerosis. For this reason, study of the accelerated disease may aid understanding of atherogenesis in general. Unraveling the basic pathobiology of these clinically important arterial diseases should lay the groundwork for rational design of selective therapeutic strategies to prevent or retard their development.

Animals↗