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Pressure-flow loops and instantaneous input impedance in the thoracic aorta: another way to assess the effect of aortic bypass graft implantation on myocardial, brain, and subdiaphragmatic perfusion.

BACKGROUND: The serious disturbances in ventriculoarterial coupling after thoracic aorta bypass grafting are addressed through aortic entry impedance in the frequency domain from flow-pressure waves. We designed a method for synthesizing pressure and flow waves to evaluate opposal to aortic flow along the cardiac cycle, addressing myocardial, brain, and visceral tissue perfusions from pressure-flow hysteresis loops and forward-backward aortic entry impedance in the ascending aorta, transverse aortic arch, and distal descending aorta, respectively, before and after extra-anatomic grafting of the descending aorta in the swine. METHODS: Twelve pigs underwent extra-anatomic grafting (woven double-velour prosthesis, 18-mm diameter), bypassing the descending aorta. Periarterial flow and endovascular pressure signals were mathematically synthesized (error minimization) to yield continuous functions of flow, pressure along the cardiac cycle before treatment for mean hemodynamics, pressure-flow hysteresis loops, and aortic entry impedance. RESULTS: Grafting of the descending aorta overshadowed pressure-flow hysteresis loops in the ascending aorta by shortening maximum pressure delay on maximum flow and diastolic flow reversal. Clamping of the descending aorta substantially restored hemodynamics in the ascending aorta, although the diastolic flow decrease was accelerated. Identical processes developed in the transverse aorta. Subdiaphragmatic descending aortic flow was flattened after grafting and restored, although thickened, after clamping of the descending aorta. Flow wave peak was framed by a diastolic aortic entry impedance peak, which was damped along the transverse aortic arch (aortic entry impedance peak in the ascending aorta, 1700 +/- 102 kN x s x m(-5); aortic entry impedance peak in the descending aorta, 292 +/- 45 kN x s x m(-5); P <.05). After grafting, the aortic entry impedance peak was transferred to early systole (aortic entry impedance peak in the transverse aortic arch, 2104 +/- 94 kN x s x m(-5); aortic entry impedance peak in the descending aorta, 450 +/- 75 kN x s x m(-5); P <.05). Clamping of the descending aorta attenuated the early systolic aortic entry impedance peak (aortic entry impedance peak in the transverse aortic arch, 1269 +/- 104 kN x s x m(-5); aortic entry impedance peak in the descending aorta, 491 +/- 75 kN x s x m(-5); P <.05), although aortic entry impedance in the descending aorta remained higher than before grafting (P <.05). Specifically, the backward flow ascending aorta to coronary trunks generated a backward aortic entry impedance peak (2234 +/- 350 kN x s x m(-5)) superimposed onto the forward aortic entry impedance peak with asymptotic boundaries that diminished after grafting and further enlarged after clamping of the descending aorta. CONCLUSIONS: Hemodynamic opposition of grafting of the descending aorta are specific to the aortic site and cardiac cycle and are dependent on clamping of the descending aorta. Our approach to thoracic aorta hemodynamics could enable optimization of bypass grafting.

Analysis of Variance↗

Responses of IL-18- and IL-18 receptor-deficient pancreatic islets with convergence of positive and negative signals for the IL-18 receptor.

Pancreatic islets contain cells that produce IL-18 and cells that express IL-18 receptors. In experimentally induced diabetes, islet failure correlates with IL-18 levels and diabetes is delayed with blockade of endogenous IL-18. We studied islet-derived IL-18 and responses to IL-18 in a mouse model of islet allograft transplantation. In vitro, IL-18-stimulated islets produced nitric oxide, which closely matched islet apoptosis. By neutralizing IL-18 activity with IL-18 binding protein (IL-18BP), we observed that islets produce bioactive IL-18. In vivo, transgenic mice overproducing IL-18BP (IL-18BP-Tg) exhibited delayed hyperglycemia induced by beta cell toxic streptozotocin. Similarly, cultured IL-18BP-Tg islets were protected from streptozotocin-induced apoptosis. In the transplant model, islets grafted from WT to IL-18BP-Tg mice achieved prolonged normoglycemia (P = 0.031). Improved graft function was also observed by using IL-18-deficient islets transplanted into WT recipients, demonstrating that endogenous, islet-derived IL-18 mediates IL-18-driven graft damage. Unexpectedly, islets from mice deficient in IL-18 receptor alpha chain (IL-18R) exhibited rapid graft failure (P = 0.024; IL-18- versus IL-18R-deficient grafts in WT recipients). In related studies, IL-18R-deficient splenocytes and macrophages produced 2- to 3-fold greater amounts of IL-18, TNFalpha, macrophage inflammatory protein 1, macrophage inflammatory protein 2, and IFNgamma upon stimulation with Con A, Toll-like receptor 2 agonist, or anti-CD3 antibodies. These data reveal a role for islet-derived IL-18 activity during inflammation-mediated islet injury. Importantly, discrepancies between IL-18- and IL-18R-deficient cells suggest that IL-18Ralpha chain is used by an inflammation-suppressing signal.

Animals↗

Prognostic value of eustachian tube function in pediatric tympanoplasty.

Poor eustachian tube function and prevalence of infectious ear disease are thought to be the reasons for less successful outcome associated with tympanoplasty in children. Since both of these factors are related to age, identification of those patients who may benefit by delaying the surgery has been a concern to otolaryngologists. In an effort to investigate the role of eustachian tube function on the outcome, we tested the tubal function in 63 ears (56 children) undergoing tympanoplasty for central perforations. In 49 ears (78%), the graft took; of these, 33 had good middle-ear function, 8 developed persistent or recurrent otitis media, and 8 had severe retraction or atelectasis. There was a significant association (p less than 0.01) between outcome and preoperative tubal function as determined by combining the active and passive function parameters. However, the prognostic value of tubal function testing was low; predictive values for success and lack of success being 68% and 56%, respectively. Other factors, such as graft placement (medial or lateral) contralateral ear status, and child's age, were not associated with outcome. Consistent with other studies, good eustachian tube function was shown to predict good outcome, but poor tubal function was not helpful in predicting poor outcome.

Adolescent↗

Long-term effects of bone marrow transplantation.

As increasing numbers of children are surviving beyond the 1st decade after marrow transplantation and increasing numbers of children are receiving marrow transplants each year, the delayed effects related to the transplant procedure itself, the original disease, and/or the transplant preparative regimen are becoming apparent. Late effects related to the transplant procedure include those of engraftment stability, the chronic immunosuppression of chronic graft-versus-host disease and delayed immunologic recovery. Recurrent disease is the major late effect related to the patient's original disease. The late effects which may be related to previous therapy administered and/or the transplant preparative regimen include abnormalities of neuroendocrine function, ocular problems, dental developmental abnormalities in young children, central nervous system dysfunction and the development of secondary malignancies. To improve the quality of life of marrow transplant recipients and to prevent some of the growth and development abnormalities which may occur, an awareness of the problems encountered to date is needed.

Bone Marrow Transplantation↗

Fractional mean transit time in transplanted kidneys studied by technetium-99m-DTPA: comparison of clinical and biopsy findings.

UNLABELLED: To determine the usefulness of fractional mean transit time (MTT) in the differential diagnosis of postrenal transplant complications, 99mTc-DTPA was used to evaluate differences in MTT between the outer zone (cortical nephron) and middle zone (juxtamedullary nephron, calcyces and cortical nephron) of the kidney. It is well known that acute rejection is characterized by delayed cortical transit time, whereas cortical nephron function is well maintained and juxtamedullary function is impaired after renal ischemia. METHODS: Technetium-99m-DTPA fractional MTT was determined by deconvolution analysis of 89 renograms obtained within 5 days of the date of kidney graft biopsy and evaluation. RESULTS: Outer zone MTT was significantly shorter than middle zone MTT in normals (2.7 +/- 0.4 versus 3.0 +/- 0.6 min, n = 22, p < 0.001), acute tubular necrosis (3.4 +/- 1.1 versus 3.6 +/- 1.4 min, n = 19, p < 0.01), chronic rejection (3.9 +/- 1.5 versus 5.0 +/- 2.3 min, n = 14, p < 0.001) and obstruction (4.1 +/- 0.6 versus 8.9 +/- 3.4 min, n = 13, p < 0.001). In contrast, outer zone MTT was significantly longer than middle zone MTT in acute rejection (4.8 +/- 3.2 versus 4.2 +/- 2.5 min, n = 21, p < 0.05). CONCLUSION: Fractional MTT was demonstrated to be useful in differentiating acute rejection and ATN in transplanted kidneys.

Adolescent↗

[Intratemporal surgery of the facial nerve. Apropos of 34 cases].

The results of facial nerve surgery in the temporal bone have been evaluated in a review of 34 cases (19 decompressions and 15 reparations). Decompressions of immediate and complete facial paralysis by fracture of the temporal bone that have achieved a good motor recovery resulted from early surgery before the 21st day (50% of grades I and II, 50% of grades III). After this delay, facial recovery did not reach grades I and II any longer. In case of nervous interruption of traumatic origin or after tumoral ablation, direct restoration of continuity by an intermediary grafting fixed with fibrin glue enabled the recovery of a facial function of grade III in 87.5% of the cases. These results point out the importance of an early exploration of traumatic facial paralysis before the end of the third week, and the interest of using a cable graft fixed with fibrin glue to repair directly the facial nerve.

Adolescent↗

A comparison of early and late reconstruction of malunited fractures of the distal end of the radius.

We retrospectively evaluated the results for ten patients in whom a malaligned fracture of the distal end of the radius had been treated with early reconstruction (an average of eight weeks [range, six to fourteen weeks] after the injury) consisting of an osteotomy through the site of the fracture, autogenous cancellous iliac-crest bone-grafting, and internal fixation. The results for these patients were compared with those for ten patients in whom functional limitation after complete healing of a fracture of the distal end of the radius in a malreduced position had been treated with late reconstruction (an average of forty weeks [range, thirty to forty-eight weeks] after the injury) consisting of an osteotomy, corticocancellous bone-grafting, and internal fixation. The average duration of follow-up was forty-eight months (range, twenty to 120 months) after the early reconstructions and thirty-four months (range, twenty-four to forty-eight months) after the late reconstructions. After the early reconstructions, flexion of the wrist averaged 45 degrees; extension of the wrist, 52 degrees; pronation of the forearm, 79 degrees; and supination of the forearm,77 degrees, compared with 42, 45, 77, and 68 degrees, respectively, after the late reconstructions. Grip strength averaged forty-two kilograms after the early reconstructions, compared with twenty-five kilograms after the late ones. One patient from each cohort had mild pain in the radiocarpal joint. According to the scale of Fernandez, there were seven excellent and three good results after the early reconstructions, and one excellent, seven good, and two fair results after the late reconstructions. Complications included a rupture of the extensor pollicis longus tendon twelve weeks after one of the early reconstructions, persistent pain at the donor site of the iliac-crest bone graft after a late reconstruction, and a delayed union that necessitated a second procedure after another late reconstruction. We believe that the results of early and late reconstruction of malunited fractures of the distal end of the radius are comparable. For patients who have radiographic characteristics that are predictive of persistent functional limitation, early reconstruction is technically easier and reduces the over-all period of disability.

Adult↗

Functional activity of anti-C6 antibodies elicited in C6-deficient rats reconstituted by liver allografts. Ability to inhibit hyperacute rejection of discordant cardiac xenografts.

A critical role of the complement membrane attack complex (C5b-9) in mediating hyperacute rejection has been demonstrated previously in fully C6-deficient PVG (C-)(RT1c) rats that reject guinea pig cardiac xenografts at a delayed tempo (45 +/- 9 hr; n=16) compared with C6-sufficient PVG (C+)(RT1c) hosts (0.5 +/- 2 hr; n=6). We have investigated whether selective depletion of C6 from Lewis rats by antibody therapy prevents hyperacute rejection. A polyclonal rat-antirat C6 antibody was induced in PVG (C-) recipients by orthotopic liver transplants from congenic PVG (C+) donors. These liver grafts produced high levels of C6 that reconstituted the complement function of PVG (C-) hosts by 7 days, but the recipients responded within 28 days with the synthesis of an IgG1 antibody to rat C6. The antiserum inhibited hemolytic complement activity of Lewis (RT1(1)) rats in vivo and in vitro. The effect of C6 depletion on Xg survival was investigated by injecting Lewis rats with 2 ml of rat-antirat C6 antiserum before and 1 ml after reperfusion of the guinea pig cardiac xenograft. Lewis rats rejected guinea pig cardiac xenografts after treatment with this rat-antirat C6 antiserum in 38 +/ -11 hr (n=3). Treatment with normal control sera from PVG (C-) rats did not prolong guinea pig cardiac xenograft survival in the Lewis rats (1 +/- 0.7 hr; n=3)(P<0.0043). Injection of 3 ml of the IgG fraction purified from the rat-antirat C6 antibody (33 mg/ml) prolonged xenograft survival to 13.6 +/- 4 hr (n=4) compared with the survival of 0.61 +/- 0.3 hr (n=4) after injection of control rat IgG (33 mg/ml) (P<0.005). These results demonstrate that specific depletion of C6 by antibody therapy has a significant effect on guinea pig cardiac xenograft survival in the Lewis rat. These findings further suggest that C6 depletion may be beneficial to patients undergoing hyperacute rejection of xenografts or allografts.

Animals↗

Major histocompatibility complex-mismatched allogeneic bone marrow transplantation using perforin and/or Fas ligand double-defective CD4(+) donor T cells: involvement of cytotoxic function by donor lymphocytes prior to graft-versus-host disease pathogenesis.

Experimental allogeneic bone marrow transplantation (BMT) models using cytotoxic single-deficient (perforin/granzyme or Fas ligand [FasL]) and cytotoxic double-deficient (cdd) CD4(+) donor T cells have previously demonstrated roles for both effector pathways in graft-versus-host disease (GVHD). In the present study, the role of CD4-mediated antihost cytotoxicity in a GVH response is further examined across a complete major histocompatibility complex class I/II mismatch. As predicted, a double cytotoxic deficiency resulted in a clear delay in GVH-associated weight loss, clinical changes, and mortality. Interestingly, analysis of donor T-cell presence in 5.5-Gy recipients soon after BMT demonstrated that the double cytotoxic deficiency resulted in a marked decrease in donor CD4 numbers. Transplantation of singularly perforin- or FasL-deficient donor CD4(+) T cells demonstrated that the absence of FasL was responsible for the markedly diminished CD4 number in recipient lymph nodes and spleens soon after BMT. However, increasing recipient total body irradiation conditioning (11.0 Gy) abrogated the decrease in FasL-defective B6-cdd and B6-gld CD4 numbers. Thus, the decrease was not a result of inherent CD4 defects, but was probably attributable to host resistance. Consistent with these observations, transplantation into 11.0-Gy recipients resulted in identical GVH lethality by equal numbers of B6 wild-type, B6-cdd, and B6-gld CD4(+) T-cell inoculum. In total, the findings indicate that aggressive host conditioning lessens the requirement for donor CD4(+) cytotoxic function in GVH responses soon after BMT. The present results thus support the notion of a role for cytotoxic effector function in donor CD4(+) T cells prior to GVH-induced tissue injury.

Animals↗

[Preliminary study on effect of ganhuang injection on reject reaction of xenograft].

OBJECTIVE: To study the effect of Ganhuang Injection (GHI) on reject reaction of xenograft. METHODS: RT-PCR technique was used to detect the activated relevant gene expression in porcine endothelial cells (PEC), and 51Cr releasing method was used to test the killing and adhesion action of NK cells. RESULTS: The normal human serum and human NK-92 cell could up-regulate the mRNA expressions of E-selectin and IL-1 alpha gene in PEC, showing the PEC activating action, GHI could inhibit these activated gene expressions. Cyto-toxic experiment showed that GHI could also inhibit the cytotoxicity of NK cell on PEC dose-dependently, which was in accord with its inhibition on adhesive action of NK on PEC. CONCLUSION: GHI could inhibit not only the PEC activation in hyperacute rejection, but also the function of NK cells in delayed xenograft rejection.

Animals↗

Xenografts of porcine islets immunoprotected in hollow fibres reduce the incidence of diabetes in non-obese diabetic mice.

Non-obese diabetic (NOD) mice develop an autoimmune disease with a long prodromal period and constitute a model for investigating the prevention of human insulin-dependent diabetes mellitus. Since insulin injected prophylactically has been shown to reduce incidence of diabetes in NOD mice, we tested a new strategy consisting of prophylactic xenografts of porcine pancreatic islets immunoprotected in semipermeable hollow fibres. Female NOD mice were transplanted twice (at 60 and 180 days of age) with islet-containing or empty fibres. Within the group grafted with protected islets, the incidence of diabetes was reduced (37 vs 75%; p < 0.01), the onset of disease was delayed (p < 0.02), and the severity of lymphocytic inflammation of endogenous islets was reduced (p < 0.02). When already diabetic mice were not taken into account for analysis, blood glucose level was slightly lower in those grafted with islet-containing fibres (p < 0.04). Graft function was also evidenced by HPLC separation of porcine insulin in NOD sera. Histological and perifusion studies of fibres retrieved from recipients confirmed immunoprotection. During co-transfer, T splenocytes from mice grafted with islet-containing fibres were able to reduce the capacity of T cells from diabetic donors to adoptively transfer the disease (p < 0.01). Antigens for islet-cell autoantibodies (ICA) in pancreata from both groups were compared by immunofluorescence with the same ICA-positive human sera to ensure that differences were due to antigen quantitative changes. These antigens, which could serve as an index of a possibly more extensive antigen beta-cell rest, were decreased (p < 0.01) in mice grafted with protected islets. Reduction of diabetes and insulitis following early islet transplantation may thus be due to generation of cellular mechanisms that actively suppress disease, and possibly in part to a decrease in antigens which make beta cells less vulnerable to autoimmune aggression. These effects can be obtained with xenogeneic islets protected in hollow fibres, thereby eliminating the need for immunosuppression. Based on the concept of prophylactic insulin therapy, this form of insulin administration offers a controlled means of delivering insulin to meet the physiological needs of recipients.

Aging↗

Surgical implications of snakebites.

OBJECTIVE: Snakebites are a common problem in the pediatric age group. Local complications such as necrosis and compartment syndrome threaten limb survival even after control of systemic manifestations. Few recommendations exist about the nature and timing of surgical treatment. METHODS: A retrospective review of all children with snakebites presenting to the hospital was undertaken over a 6-year period. Records were reviewed with special emphasis on the type of surgical lesions seen and the treatment offered and their results. RESULTS: 44 of the 58 children required some form of local therapy. In the majority conservative treatment was successful. 28% of the patients needed debridement for local necrosis, and only 5 needed a skin graft, with good functional results over a period of 1 to 45 days. One child underwent an above knee amputation. Patients who required surgical intervention received significantly more vials of antivenin. CONCLUSION: Local complications of snakebite are frequent, but can be managed conservatively. Delayed excision of the resultant local necrosis is associated with good outcomes. The need for fasciotomy is rare.

Adolescent↗

Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases.

This is a review of the clinical responses and prospectus of new therapies following use of allogeneic hematopoietic stem cell transplantation for the treatment of the following disorders: Hurlers syndrome (MPS 1-H), globoid cell leukodystrophy (GLD; Krabbes disease), adrenoleukodystrophy, metachromatic leukodystrophy, Wolmans disease, I-cell disease (mucolipidosis II; MLS-II), alpha-mannosidosis, fucosidosis, Niemann-Pick B/A disease, Slys disease (MPS VII), Gauchers disease (Gaucher-II-III), Battens disease, Farbers disease, Sanfilippo syndrome (MPS-III), Hunters disease (MPS-II), Maroteaux-Lamy syndrome (MPS-VI), and aspartylglucosaminuria (AGU). Over 500 patients with lysosomal and peroxisomal metabolic storage diseases due to deficiency of primary enzymes have been treated with hematopoietic stem cell transplantation since the initial patient was treated a quarter of century ago. Normal enzymatic activity has been robust and continuous over these years without the need for any medication. Proof of principle has been reported for multiple positive effects including that of the reconstruction of the central nervous system. Furthermore, the excellent engraftment rate along with significantly diminished graft-vs-host-disease needs to be emphasized. The genetic diseases enumerated above have remarkable differences from those discussed elsewhere in this issue of Seminars in Immunopathology. Each has a greater genetic heterogeneity. Misdiagnosis resulting in delay of treatment and further decline of function and ultimate quality of life occurs almost all the time. Neonatal screening of these diseases will be mandatory to vastly improve outcomes. Plans are being implemented to use dried blood spots on filter paper, as is commonly done for many other genetic diseases. Many new therapies are being adopted which should enhance positivity and acceptance of treatment by hematopoietic stem cell transplantation.

Adrenoleukodystrophy↗

Laminin alpha5 chain is required for intestinal smooth muscle development.

Laminins (comprised of alpha, beta, and gamma chains) are heterotrimeric glycoproteins integral to all basement membranes. The function of the laminin alpha5 chain in the developing intestine was defined by analysing laminin alpha5(-/-) mutants and by grafting experiments. We show that laminin alpha5 plays a major role in smooth muscle organisation and differentiation, as excessive folding of intestinal loops and delay in the expression of specific markers are observed in laminin alpha5(-/-) mice. In the subepithelial basement membrane, loss of alpha5 expression was paralleled by ectopic or accelerated deposition of laminin alpha2 and alpha4 chains; this may explain why no obvious defects were observed in the villous form and enterocytic differentiation. This compensation process is attributable to mesenchyme-derived molecules as assessed by chick/mouse alpha5(-/-) grafted associations. Lack of the laminin alpha5 chain was accompanied by a decrease in epithelial alpha3beta1 integrin receptor expression adjacent to the epithelial basement membrane and of Lutheran blood group glycoprotein in the smooth muscle cells, indicating that these receptors are likely mediating interactions with laminin alpha5-containing molecules. Taken together, the data indicate that the laminin alpha5 chain is essential for normal development of the intestinal smooth muscle and point to possible mesenchyme-derived compensation to promote normal intestinal morphogenesis when laminin alpha5 is absent.

Animals↗

A technique to quantitate motor recovery following nerve grafting.

Sixteen patients were evaluated retrospectively following grafting of an upper extremity peripheral nerve injury. In addition to the standard subjective muscle grading, the force of reinnervated muscle groups was quantitatively measured using force transducers, and reported relative to the contralateral side. Patients recovered a median motor grade of M3, which correlated to a 32% recovery of muscle force of the contralateral side. M3 and M4 motor grades encompassed a large range of actual muscle force: M3 correlated with a recovered force that ranged from 17% to 42%, M4 with a range of 66% to 79%. The percent force of motor recovery decreased significantly with longer delays to nerve grafting, even when controlling for the severity of the injury. Similarly, recovery of muscle force decreased when longer segments of nerve grafts were used. Testing the return of muscle strength after peripheral nerve injuries with a standardized objective system that compares function to the uninjured side enhances the sensitivity of evaluating nerve regeneration and provides a measurement system that can facilitate the comparison of different nerve repair techniques.

Adolescent↗

Vascularization of purified pancreatic islet-like cell aggregates (pseudoislets) after syngeneic transplantation.

To clarify whether avascular purified endocrine cell aggregates derived from islets of Langerhans (pseudoislets) revascularize similarly to what is known for intact pancreatic islet grafts, we studied the process of angiogenesis and revascularization of syngeneically transplanted pseudoislets using intravital fluorescence microscopy. Pseudoislets were composed of pure beta-cells (B) or non-beta-cells (NB), as well as of mixed beta- and non-beta-cells (B/NB; 70/30%) or nonsorted-cells (NC), and were transplanted into the dorsal skinfold of Syrian golden hamsters. Intact islet grafts served as controls. At day 6 after transplantation, microvascularization of all types of pseudoislets was found to be less than in controls, as indicated by a reduced number of transplants that contained newly formed microvessels (take-rate: B, 38.8; NB, 38.7; B/NB, 43.8; and NC, 40.3% vs. intact islet grafts, 71.9%; P < 0.01). Moreover, those pseudoislets that had developed a microvascular network revealed a significantly lower functional capillary density (145.8+/-49.5 to 241.0+/-47.5 cm(-1) vs. intact islet grafts: 459.8+/-65.6 cm(-1); P < 0.05). After 20 days, the take-rate of pseudoislets was still lower (B, 67.4; NB, 45.3; B/NB, 48.4; and NC, 64.2%) when compared with intact islet grafts (88%; P < 0.05); however, islet-like aggregates with vascularization now showed an islet-specific glomerulus-like network of capillaries with a functional capillary density (498.5+/-49.1 to 601.4+/-124.0 cm[-1]) similar to that of intact islet grafts (644.3+/-26.8 cm[-1]). We conclude that the dissociation of pancreatic islets, followed by reaggregation of the purified endocrine cells to islet-like clusters (pseudoislets), delays the process of angiogenesis and revascularization after free transplantation; however, this does not influence the capacity to form an intact islet-specific microvasculature (angio-architecture), which appears to be independent from the cellular composition of pseudoislets.

Animals↗

[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↗

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↗