Face Transplantation: Partial Graft Loss of the First Case 10 Years Later.

Ten years after the first face transplantation, we report the partial loss of this graft. After two episodes of acute rejection (AR) occurred and completely reversed in the first posttransplantation year, at 90 months posttransplantation the patient developed de novo class II donor-specific antibodies, without clinical signs of AR. Some months later, she developed several skin rejection episodes treated with steroid pulses. Despite rapid clinical improvement, some months later the sentinel skin graft underwent necrosis. Microscopic examination showed intimal thickening, thrombosis of the pedicle vessel, and C4d deposits on the endothelium of some dermal vessels of the facial graft. Flow magnetic resonance imaging of the facial graft showed a decrease of the distal right facial artery flow. Three steroid pulses of 500 mg each, followed by intravenous immunoglobulins (2 g/kg), five sessions of plasmapheresis, and three cycles of bortezomib 1.3 mg/m2 , were administered. Despite rescue therapy with eculizumab, necrosis of the lips and the perioral area occurred, which led to surgical removal of the lower lip, labial commissures, and part of the right cheek in May 2015. In January 2016, the patient underwent conventional facial reconstruction because during the retransplantation evaluation a small-cell lung carcinoma was discovered, causing the patient's death in April 2016.

Medico legal aspects on neuromonitoring in thyroid surgery: informed consent on malpractice claims.

AIM: The purpose of this paper is to provide a forensic profile framework of neuromonitoring in thyroid surgery, regarding the information given to the patient and its classification as part of professional liability in the event of recurrent injury. METHOD: Evaluation and reflections on the required behaviour of the surgeon on providing details on the operation before the informed consent is given and to outline the possible legal implications regarding professional liability as a result of recurrent injury. In particular, if it is an obligation to inform the patient about using this method and if it is possible for the surgeon to freely choose whether to employ this method, which is still burdened by a certain percentage of error and for that reason it cannot be defined a "standard of care". RESULTS: To recognize neuromonitoring the role of standard of care in surgery of the thyroid means attribute a role of method able to avoid the surgeon to cause iatrogenic damage to the laryngeal nerve. For the foregoing reasons that is not true, determining false positives and false negatives, and this can be a double edged sword for the surgeon. CONCLUSIONS: Although the progress in the field of thyroid surgery made in the last decade, currently there is no scientific reassuring evidence to completely avoid the possibility of producing an iatrogenic lesion of the laryngeal nerve. Information given to the patient prior to surgery should respect the requirements of completeness, freedom and honesty in order to allow the patient to self-determination.

Kidney graft outcome and quality (after transplantation) from uncontrolled deceased donors after cardiac arrest.

The use of uncontrolled deceased donors after cardiac arrest (uDDCA) has been developed in France to compensate for organ shortage. The quality of these kidneys remains unclear. We analyzed kidney graft function and histology from 27 uDDCA and compared them with kidneys from 30 extended criteria donors (ECD) and from 24 simultaneous pancreas kidney (SPK) donors as a control group of optimal deceased donors. Kidneys from ECD and SPK donors were preserved by static cold storage while kidneys from uDDCA were preserved by pulsatile perfusion. The uDDCA graft function at 3 years posttransplantation (estimated with MDRD and measured with inulin clearance) did not differ from that of the ECD group (eGFR 44.1 vs. 37.4 mL/min/1.73 m(2) , p = 0.13; mGFR 44.6 vs. 36.1 mL/min/1.73 m(2) , p = 0.07 in the uDDCA and ECD groups, respectively). The histological assessment of 3-month and 1-year protocol biopsies did not show differences for interstitial lesions between the uDDCA and ECD grafts (IF score at M3 was 30 vs. 28% and at M12 36 vs. 33%, p = NS). In conclusion, the results at 3 years with carefully selected and machine-perfused uDDCA kidneys have been comparable to ECD kidneys and encourage continuation of this program and development of similar programs.

Long-term follow-up in composite tissue allotransplantation: in-depth study of five (hand and face) recipients.

Composite tissue allotransplantations (CTAs) have clinically shown little, if any, evidence of chronic rejection. Consequently, the effect of chronic rejection on bones, joints, nerves, muscles, tendons and vessels may still have undescribed implications. We thoroughly assessed all allograft structures by histology, magnetic resonance imaging, ultrasonography and high resolution peripheral quantitative computed tomography scan in four bilateral hand-grafted patients (10, 7, 3 and 2 years of follow-up, respectively) and in one facial allotransplantation (5 years of follow-up). All the recipients presented normal skin structure without dermal fibrosis. Vessels were patent, without thrombosis, stenosis or intimal hyperplasia. Tendons and nerves were also normal; muscles showed some changes, such as a variable degree of muscular hypotrophy, particularly of intrinsic muscles, accompanied by fatty degeneration that might be related to denervation. In the majority of hand-grafted patients graft radius and recipient tibia showed a decrease in trabecular density, although in the graft radius the alterations also involved the cortices. No deterioration of graft function was noted. In these cases of CTA no signs of chronic graft rejection have been detected. However, the possibility that chronic rejection may develop in CTA exists, highlighting the necessity of close continuous follow-up of the patients.

Role of flow magnetic resonance imaging in the monitoring of facial allotransplantations: preliminary results on graft vasculopathy.

Chronic vascular rejection characterized by the myointimal proliferation of smooth muscle cells that progressively obstruct the arterial graft lumen may become the main cause of long-term graft loss in vascularized composite allotransplantation (VCA), as observed in solid organ transplantation. As such, new diagnostic tools are required. The objective of this study was to evaluate the usefulness of flow magnetic resonance imaging (MRI) in the qualitative and quantitative monitoring of VCA in three patients transplanted between 2005 and 2012. Seven flow MRI acquisitions were performed concurrently with standardized clinical and histological monitoring between 2015 and 2017. A progressive reduction in the average flow rate and intraluminal diameter of the arterial pedicle of the grafts was demonstrated. During follow-up, two patients developed chronic vascular rejection requiring partial resection of the graft. For these patients, flow MRI acquisitions were characterized by a significant reduction in vascular signal, with a reduction in intravascular flow prior to anatomical injury. The results of this study confirm the feasibility of reproducible, non-invasive, and non-operator-dependent morphometric and haemodynamic radiological analysis, providing clinicians with new information on the vascular status of VCA over time and offering the prospect of an imaging technique specific to vascular outflow.

Kidney preservation with IGL-1 solution: a preliminary report.

The University of Wisconsin (UW) solution is the most commonly used preservation solution. However, a new preservation solution-IGL-1-contains an inversion of K and Na concentrations and substitution of polyethylene glycol for hydroxyethyl starch in the UW solution. The present study is the first clinical experience on the outcome of kidneys preserved in IGL-1 solution. From June 2003 to June 2004, 119 cadaveric kidneys were retrieved and stored in IGL-1 solutions; among the 119 organs, this study includes 37 IGL-1-preserved kidneys that were locally transplanted versus 33 kidneys stored in University of Wisconsin (UW) solution that were also locally transplanted. The groups were comparable with regard to donor and recipient characteristics. Renal function outcome was evaluated by comparing delayed graft function (DGF) rates, the evolution of serum creatinine, daily urine output, and creatinine clearance. Biopsies were performed after reperfusion to evaluate apoptosis. The incidence of DGF was 5.71% among IGL-1 kidneys and 13.79% among UW kidneys. Creatinine values were significantly lower among the IGL-1 group from 2 to 14 days postoperative and at 1 month. Daily urinary output did not show any significant differences between the two groups. IGL-1 kidneys had a superior creatinine clearance during the first 15 postoperative days compared to UW kidneys. Kidneys preserved in IGL-1 solution showed fewer apoptotic cells compared to kidneys preserved in UW solution. This preliminary report suggests a superiority of IGL-1 for the immediate outcome of transplanted kidneys.

Serological markers of recurrent beta cell destruction in diabetic patients undergoing pancreatic transplantation.

BACKGROUND: Besides alloimmunity to transplanted pancreatic tissue, recurrent autoimmune beta cell destruction is an additional limitation to successful clinical pancreatic allografts in type 1 diabetic patients. METHODS: We studied the prevalence of autoantibodies to glutamate decarboxylase (GAD) 65 and tyrosine phosphatase (IA-2) in 68 C-peptide-negative diabetic patients receiving pancreatic allografts. Sera from patients were obtained immediately before grafting. A second blood sample was analyzed at the time of graft failure in patients who returned to hyperglycemia and during the same follow-up period in those who experienced a functional pancreatic allograft. Patients were classified according to clinical outcome into chronic graft failure (group A, n=20), acute graft failure and/or arterial thrombosis (n=7), or functional pancreatic graft (group C, n=41). Sera from patients were screened for the presence of specific autoantibodies using an islet cell autoantibody assay, a combi-GAD and IA-2 test, and individual GAD and IA-2 assays. RESULTS: Patients from group A had significantly higher combi-test values than patients from group C (13+/-16 vs. 4.5+/-12 units, P<0.02) and higher anti-GAD65 antibody (Ab) levels (0.19+/-0.3 vs. 0.04+/-0.13 units, P<0.01) immediately before grafting. After graft failure in group A, both anti-GAD65 and anti-IA-2 Ab levels increased from baseline, but only the increase in anti-IA-2 Ab levels reached statistical significance (0.28+/-0.12 vs. 15+/-34, P=0.03). When compared with group C, patients from group A had higher anti-GAD65 Abs (0.29+/-0.35 vs. 0.05+/-0.16, P<0.001) after graft failure. Interestingly, the number of double-Ab-positive patients rose from 5% to 35% in group A, whereas it remained at 5% in group C. In pancreatic transplants with bladder drainage, the presence of anti-GAD65 and/or anti-IA2 Abs was not associated with a reduction in urinary amylase levels. This suggests that a loss of endocrine function was not associated with exocrine failure in patients from group A. CONCLUSIONS: We can conclude from the present study that peripheral autoimmune markers are useful in diabetic patients receiving pancreatic allografts.

The beta 1-adrenoceptor antagonist, betaxolol, is not released from the heart of the anaesthetized dog during sympathetic nerve stimulation.

1. We investigated the hypothesis that the beta 1-adrenoceptor antagonist, betaxolol, can be accumulated by cardiac sympathetic nerve endings and then released together with noradrenaline during accelerans nerve stimulation. 2. Dogs were chronically treated with betaxolol (1 mg kg-1 daily, s.c.) for 7 days. Twenty four hours after the last dose, there was a significant retention of betaxolol in the heart of these dogs treated chronically with the beta 1-adrenoceptor antagonist. However, during in vivo accelerans nerve stimulation, the concentration of betaxolol in the coronary sinus was not modified, whereas the noradrenaline concentration increased significantly. 3. Chronic betaxolol treatment antagonized the tachycardia induced by electrical stimulation of the cardiac accelerator nerves or by intravenous isoprenaline. However, the tachycardia induced by nerve stimulation was not antagonized to a greater extent than that induced by isoprenaline. 4. These findings are discussed in relation to a similar in vivo study in dogs treated with propranolol, in which the drug was found to be released into the coronary circulation during stimulation of the accelerans nerve.

Evidence of pituitary adenylate cyclase activating polypeptide (PACAP) in pancreatic islet cells by confocal microscopy.

Several studies have shown that pituitary adenylate cyclase activating polypeptide (PACAP) stimulates at very low concentration insulin release from pancreatic beta cells. In addition, PACAP has been evidenced in pancreatic nervous fibers surrounding the islets, the core of the islet, and the capillaries. The aim of the present study was to demonstrate internalization of PACAP in pancreatic islet cells. Pancreatic islets were obtained from Wistar rat pancreata by modified Lacy's isolation method. The isolated islets were incubated in the presence of Fluo-PACAP 27, a fluorescent ligand specific for PACAP receptors. At the end of incubation the islets were fixed in paraformaldehyde and then observed by confocal microscope. Fluo-PACAP 27 was internalized into pancreatic islet cells, and this process was time- and temperature-dependent (37 degrees C). The fluorescent molecules converged toward the nucleus where an intense fluorescence was evidenced after 60 minutes. Incubation with phenyl arsine oxide as well as with PACAP 6-38, a receptor antagonist, prevented the internalization process. Further studies are required to explain the internalization process of PACAP 27 into the nucleus of pancreatic islet cells.

Electrical stimulation releases 3H-betaxolol from rat atrial slices: possible role of noradrenergic nerves.

Under in vitro conditions, 3H-betaxolol was accumulated in rat atrial slices, reaching a tissue-medium ratio of 12.3 +/- 1.8 ml/g. This process was temperature-dependent, but ouabain-resistant. 3H-Betaxolol accumulated in atrial slices was subsequently released by electrical stimulation. The electrically-evoked release of 3H-betaxolol was abolished in the absence of calcium, and reduced in the presence of bretylium 10 microM. After surgical sympathetic denervation by stellate ganglionectomy there was a marked reduction in the endogenous content of noradrenaline and in the retention of 3H-noradrenaline in atrial slices. The concomitant decrease in the amount of 3H-noradrenaline released by electrical stimulation following denervation was modest, although statistically significant. Following sympathetic denervation, the tissue retention of 3H-betaxolol was not significantly affected, but the release of 3H-betaxolol by electrical stimulation was considerably reduced. After pretreatment with reserpine the amount of radioactivity released by electrical stimulation from slices labelled with 3H-betaxolol or 3H-noradrenaline was markedly reduced. The tissue retention of 3H-noradrenaline was reduced to a larger extent than that of 3H-betaxolol following the administration of reserpine. The simultaneous release of noradrenaline and betaxolol by nerve stimulation observed under our experimental conditions may represent a mechanism through which betaxolol can reach selectively the postsynaptic beta 1-adrenoceptors and reinforce beta-adrenoceptor blockade in the heart.

Evidence of recurrent type I diabetes following HLA-mismatched pancreas transplantation.

Type 1 diabetes mellitus is considered as an autoimmune disease against beta cells. Diabetes recurrence after pancreas transplantation is well known in HLA-identical twins while it is rarely reported in recipients of cadaveric pancreatic grafts. In the present case report, diabetes recurrence occurred in a recipient who underwent cadaveric combined pancreas kidney transplantation. Seven years after transplantation the patient exhibited progressive hyperglycemia needing insulin therapy while the renal graft was well functioning. The diagnosis of recurrent disease was obtained on the histological features such as selective loss of beta cells without clear signs of insulitis and on the presence of markers (GAD 65 and IA-2) for humoral autoimmunity. It is intriguing that, at the time of recurrence of type 1 diabetes, the patient had stopped steroids and azathioprine, while only cyclosporine was maintained as immunosuppressive treatment. Our case report underlines the relevance of studying the humoral autoimmune response directed to islet autoantigens in cadaveric pancreas allograft recipients. Furthermore, it suggests that an efficient immunosuppressive treatment after transplantation may be able to reduce the autoimmune response against the pancreatic allograft.

Inflammatory agonists that increase microvascular permeability in vivo stimulate cultured pulmonary microvessel endothelial cell contraction.

Bovine pulmonary microvessel endothelial cells grown on a flexible substrate contract upon the addition of angiotensin II, thrombin, bradykinin, and U44069, a stable analogue of thromboxane A2. All these agents promote inflammation and increase paracellular permeability in vivo or in vitro. The contractile response is mediated by intracellular and extracellular free calcium: the response is inhibited by TMB-8, an intracellular Ca2+ chelator, and EGTA. Contraction is inhibited by trifluoroperazine, a Ca2(+)-calmodulin antagonist, and by ML-7, an inhibitor of myosin light-chain kinase. Preincubation with PMA, a protein kinase C activator, prevents contraction by angiotensin II. The inactive analogue 4-alpha-phorbol 12,13-didecanoate does not inhibit contraction. In contrast cAMP, carbacyclin (a stable PGI2 analogue), and isoproterenol, agonists known to stabilize the microvascular barrier against inflammatory agents, relax pulmonary microvessel EC. This direct evidence of the contractile potential of microvessel endothelial cells lends support to the theory that endothelial contraction leads to increased junctional permeability.

Human hand transplantation: what have we learned?

Hand transplantation may become an important procedure for upper limb functional restoration. To date, 18 patients have been undergone 24 hand operations in the world. Initial results are extremely promising; the functional results are apparently superior to those obtained with prostheses. We report on the combined French and Italian experience of six patients (eight hands), which is based on a jointly devised protocol and represents the largest available clinical series. Six male patients aged 43, 33, 35, 32, 33, and 22 years received either a single right hand-dominant transplantation (four cases) or a simultaneous double hand transplantation (two cases). The time since the amputation ranged from 3 to 22 years. The level of transplantation was at the wrist in five cases (six hands) and at the distal forearm in two cases (two hands). Cold ischemia averaged 11.5 hours. Three patients simultaneously received additional full-thickness skin taken from the donor and transplanted onto their left hip area. This skin served as a source for biopsies and as an additional area to monitor rejection (distant sentinel skin graft). The immunosuppressive protocol included polyclonal antibodies (three patients) or monoclonal anti-CD 25 antibody (three patients), tacrolimus, mycophenolate mofetil, and prednisolone. No surgical complications occurred. Skin rejection occurred at least once in all patients at a mean of 40 days postoperatively. Three patients recovered protective and some discriminative sensation in their palm and fingers. Two patients are recovering sensation, but are still in the early phases of the regenerative process, due to the short time since the transplantation. One patient was not compliant with the immunosuppressive therapy, and underwent uncontrolled rejection and reamputation.

Evaluation of new small barium alginate microcapsules.

Microencapsulation of islets of Langerhans has been proposed in order to prevent immune rejection and possible recurrence of autoimmune disease. This study introduces a fast simple one-step microencapsulation procedure which allows the production of small sized barium-alginate beads. The volume of the microcapsules produced was approximately that of the encapsulated islets. Consequently, the insulin kinetics and the oxygen diffusion were favoured, while the transplanted tissue volume was reduced. Electron microscopy and immunoisolating testing were performed to evaluate the molecular cut-off, the physical and chemical characteristics of these microcapsules. Immunohistochemical staining and perifusion experiments of microencapsulated pancreatic islets showed their viability after the encapsulation procedure as well as in vivo experiments. In fact, microencapsulated porcine islets were implanted intraperitoneally into streptozotocin-diabetic rats. The xenografts reversed the hyperglycemic state and functioned for a period ranging from 9 to 385 days. The low mannuronic acid concentration and the purity grade of the alginate, exerted a combined influence on the capsule biocompatibility as in vivo studies showed.

[A new infusion method for a prostacyclin analogue]. / Nuova tecnica di infusione di un analogo delle prostacicline.

BACKGROUND: Iloprost, a prostaglandin I2, is chemically stable and it has been successfully used by intravenous infusion in severe limb ischemia. Usually Iloprost is diluted in 0.9% sodium chloride solution and infused intravenously for six hours each day for 28 days in hospital. METHODS: In the present study after the first three days of infusion with a traditional pump in hospital, a home pump has been utilised for the infusion of Iloprost at home. This device allows the continue infusion of Iloprost at a flow rate of 2 ml/h for six days, then the pump is filled with a new solution. The home pump consists of a protective shell in polycarbonate (10 x 12 cm), 270 ml of volume, inside there is a balloon reservoir (3 membranes) which is filled with Iloprost. The structure of Iloprost does not change into the home pump as evidenced by HPLC studies and its continue infusion allows plasmatic high levels of its active isomers during the 28 days of therapy. In 30 patients, 25 men and 5 women (mean age 61 years) with Fontaine stage IIB (6), III (5) and IV (19) POAD Iloprost has been infused with the home pump. The follow-up period was 1 to 16 months. RESULTS: The results have shown 4 major amputations and 1 death, in 9 patients complete pain relief and ulcer healing, and in 6 patients only improvement in relief of rest pain and ulcers. CONCLUSIONS: All the patients appreciated this system of infusion because they had a normal life; in addition it is less expensive because the patients stay in hospital only 3 days.

Concerns on clinical application of composite tissue allotransplantation.

Composite tissue allograft has become a clinical reality: hands, vascularized femoral diaphyses, abdominal walls, a larynx have all been transplanted throughout the world. Conventional immunosuppressive protocol has shown to be sufficient and effective. Rejection has been prevented in most cases and when it did occur it was successfully reversed. Skin has been confirmed as the principal target of acute and chronic rejection. There has been no mortality or early graft losses and, particularly in hand transplantation, the survival graft rate is 91% with a follow-up period ranging from 6 months to 61 months. The side effects of immunosuppression are limited and include primarily transient hyperglycemia, an increase in creatinine values and some opportunistic infections (i.e. cytomegalovirus infection). Nerve regeneration and cortical reorganization have been demonstrated in hand transplantation. Functional results have been encouraging particularly for hand and larynx transplantation. Appropriate indications and patient selection, based particularly on patient motivation and compliance, are essential requirements for composite tissue allograft success.

[First transplantation of two hands: results after 18 months]. / Première transplantation des deux mains: résultats à 18 mois.

AIM OF THE STUDY: The previous results achieved in single hand transplantations confirmed the feasibility of this procedure and encouraged us to perform the first human double hand transplantation, which was performed in January 2000. In the present study we reported the results obtained eighteen months after transplantation. PATIENT AND METHODS: The recipient was a 33-year old man suffering from a traumatic amputation of both hands in 1996. Surgery included procurement of the upper extremities from a 18-year old multiorgan cadaveric donor, preparation of the graft and recipient's stumps, transplantation of the hands, which included bone fixation, arterial and venous anastomoses, nerve suture, joining of tendons and muscles, and skin closure. Immunosuppressive protocol included tacrolimus, prednisone and mycophenolate mofetil. An intensive rehabilitation program was performed. Follow-up included immunological tests, skin biopsies, arteriography, bone scintigraphy, electromyography and brain functional magnetic resonance imaging. RESULTS: No surgical complications, infectious complications and graft-versus-host-disease occurred. Two episodes of acute skin rejection were demonstrated and they were completely reversed increasing steroid dose. Nerve regeneration and cortical reorganization were shown. Sensorimotor recovery was encouraging and life quality improved. CONCLUSION: This double hand transplantation showed that conventional immunosuppressive protocol is effective and safe as well as that functional results are at least as good as those achieved in replanted upper extremities.

[Picotamide: prevention and therapy of diabetic vasculopathies. A double-blind clinical study]. / Picotamide: prevenzione e terapia della vasculopatia diabetica. Esperienza clinica in doppio cieco.

Picotamide is the most interesting compound of 4-OH isophthalic acid. It is effective in vitro and in vivo. Picotamide induces inhibition of platelet aggregation: it is a thromboxane synthetase inhibitor and a thromboxane receptor antagonist. Picotamide causes cyclic endoperoxide accumulation and diverts their metabolism toward PgI2 synthesis in endothelial cells. PGI2 stimulates the adenylate cyclase with cAMP synthesis which makes platelets less sensitive to aggregatory stimulation. Picotamide induces enhancement of fibrinolytic activity, with significant reduction in the level of circulating plasminogen but in the same time it does not affect antithrombin III and FDP levels. In the present study picotamide or placebo were administered in a double blind trial at 600 mg daily for six months to 51 patients effected by diabetic macro and/or microangiopathy. The patients were 38 men and 13 women, the age was between 20 and 80 years (mean age 62.34). Twenty-seven patients were affected by type I diabetes and 24 by type II diabetes. Twenty-three of these patients presented macro-angiopathic lesions, 9 only microangiopathic lesions and 13 both. Twenty-five patients received picotamide and the other 25 an identical placebo for six months. One patient manifested myocardial infarction during the wash-out period and failed to enter the study. The following determinations were carried out: at T0 clinical examination, Doppler ultrasonography, Winsor Index, laboratory parameters; after 90 days (T90) clinical examination and Winsor Index and after 180 days (T180) were repeated photoplethysmography and clinical parameters too. Patients were not only evaluated for the vascular disease of lower extremities, but also for the other complications of diabetes, as retinopathy, nephropathy, cardiac and cerebrovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Xenograft of pancreatic islets: preliminary results of a new immunoisolation method]. / Xenotrapianto di insule pancreatiche: risultati preliminari di una nuova metodica d'immunoisolamento.

Results of clinical islet transplantation remain disappointing despite the advances in islet technology. Availability of human organs and control of rejection by adequate immunosuppressive therapy remain the unsolved problems. Transplantation of xenogeneic tissue enclosed in immuno-separating membranes without immunosuppressive drugs may be a solution. In the present study porcine pancreatic islets were isolated by semiautomated method and purified utilizing discontinuous Euroficoll gradients on IBM 2991 cell separator. The porcine pancreatic islets were encapsulated with a new one-step method utilizing a home-made droplet generator. Each microcapsule contained one or two islets and microcapsule diameter was approximately that of the islets. This condition allows an optimal diffusion of insulin, glucose, nutrients and oxygen. Consequently, perifusion experiments with encapsulated porcine islets revealed a typical biphasic pattern of insulin release as it was seen in unencapsulated controls. Human erythrocytes were encapsulated and incubated with serum containing hemolysins and complement. These experiments showed that the encapsulated erythrocytes were protected against the hemolytic activity of Ig G and complement fractions. In conclusion, this encapsulation procedure allows the production of a very thin barium alginate membrane around the islets with very little increase of the total volume of transplanted tissue.