Advantages of decellularized bovine pericardial scaffolds compared to glutaraldehyde fixed bovine pericardial patches demonstrated in a 180-day implant ovine study.

Glutaraldehyde (GA)-fixed bovine pericardial patches remain the cardiovascular industry standard despite reports of degradation, thickening, inflammation, calcification and lack of tissue remodelling. Decellularization provides the opportunity to attenuate some of these immune-mediated processes. This study compared the mechanical and morphological integrity of bovine pericardium that is GA-fixated (Glycar® patches) or decellularized (BPS), using a proprietary protocol, following implantation in an ovine model. The impact of the processing methods on tissue strength and morphology was assessed prior to implantation. Pericardial patches were then implanted in the descending aorta and main pulmonary artery of juvenile sheep (n = 6 per group) for 180 days, and clinically evaluated using echocardiography. At explanation, patches were evaluated for strength, calcification and biological interaction. Histology demonstrated a wave-like appearance of well-separated collagen fibers for BPS scaffolds that provided pore sizes adequate to promote fibroblast infiltration. The collagen of the Glycar® patches showed loss of collagen fiber integrity, making the collagen densely compacted, contributing to insignificant recipient cell infiltration. The clinical performance of both groups was excellent, and echocardiography confirmed the absence of aneurysm formation, calcification and degeneration. Explanted Glycar® patches demonstrated cells in abundance within the fibrous encapsulation that separated the implant from the host tissue. More importantly, the fibrous encapsulation also contributed to patch thickening of both the explanted aorta and pulmonary patches. The decellularized pericardial scaffolds demonstrated recellularization, resistance to calcification, re-endothelialization and adequate strength after 180-day implantation. The proprietary decellularization protocol produced pericardial scaffolds that could be considered as an alternative to GA-fixed pericardial patches.

The sequential effects of a multifactorial detergent based decellularization process on bovine pericardium.

Decellularization is a promising method for obtaining extracellular matrix scaffolds (ECM) to be used as replacement material in reconstructive procedures. The effectiveness of decellularization and the alterations to the ECM vary, depending on several factors, including the tissue source, composition and density. With an optimized decellularization process, decellularized scaffolds can preserve the spatial and temporal ECM microenvironment, which play an integral role in modulating cell migration, proliferation and differentiation. The exploration of a variety of decellularization protocols has led to mixed outcomes and comparisons between decellularization protocols could not attribute these differences to any single step in a multiple-step process. This study aimed to characterize the effects of each step of a multifactorial decellularization method on the scaffold structure and mechanical integrity of bovine pericardium. Each step of the decellularization process and the effect on the tissue was assessed using hematoxylin and eosin staining, electron microscopy, total protein, ECM protein and triglyceride quantification. The biomechanical properties were assessed using uniaxial tensile strength testing. Cell lysis occurred mainly during the detergent and alcohol steps. Collagen structural damage occurred during the detergent and alcohol steps, with no significant decreased in collagen concentration. No significant damage to elastin could be shown throughout the process, however glycosaminoglycans were significantly removed by detergent treatment. Triglycerides were removed mostly by the alcohol treatment. The strength of the pericardium decreased somewhat after each step of the protocol. It is important to characterize each decellularization protocol with regards to the decellularization efficiency and the effect on the ECM proteins structure and function to accurately evaluatein vivooutcomes.

Diabetes in pancreatectomized baboons: a model for pancreatic transplantation studies.

This study was designed to assess plasma glucose levels (PLG) and insulin release in totally pancreatectomized baboons when challenged with intravenous glucose administration (IVGTT). Ten animals (Papio ursinus) were used and duodenectomy was intentionally avoided. The PLG at death was 18.0 +/- mmol/L, and the mean K-value within 3 days after pancreatectomy was 0.4% +/- 0.2%, indicating a significant impairment of glucose disappearance from the blood when compared to the control animals (P less than 0.01). Plasma insulin levels before and after stimulation with glucose were below the lowest level of insulin assay sensitivity. We conclude that in the primate, as in the dog, surgical pancreatectomy produced a reliable diabetic model, which is uniformly lethal if left untreated.

Early postoperative pancreatic endocrine function after segmental and pancreaticoduodenal allotransplantation in nonimmunosuppressed primates.

In this study we evaluated the short-term hormonal effects of segmental and whole pancreatic allotransplantation on the glucose intolerance produced by hemipancreatectomy in the primate. In hemipancreatectomized animals without grafts the K-values were reduced to 0.6 +/- 0.05, plasma insulin increased from 27.5 +/- 2.5 to 63.5 +/- 6.3 microU/ml, and glucagon levels declined from 252 +/- 29.9 to 216.5 +/- 33.0 pg/ml. Hemipancreatectomized segmental allograft recipients rendered K-values of 0.79 +/- 0.05, plasma insulin increased from 19.98 +/- 3.43 to 66.0 +/- 17.03 microU/ml, and glucagon release declined from 395.6 +/- 63.0 to 226.2 +/- 37.6 pg/ml during IVGTT postoperatively. Hemipancreatectomized, pancreaticoduodenal allograft recipients rendered K-values of 0.82 +/- 0.1, results not significantly different from hemipancreatectomized or segmental allograft recipients. Plasma insulin increased from 29.5 +/- 4.0 to 186.0 +/- 25.0 microU/ml, and glucagon release declined from 1,087.0 +/- 31.6 to 656.0 +/- 12.7 pg/ml. In summary, segmental pancreatic allotransplantation could not, in the short-term, restore the reduced K-values and hypoinsulinaemia in hemipancreatectomized primates to that of normal, unstressed controls. Although K-values of hemipancreatectomized recipients were not significantly improved, whole pancreas transplantation resulted in improved insulin release and hyperglucagonaemia during IVGTT when compared to segmental allograft recipients. The unexpected findings of hypoinsulinaemia and hyperglucagonaemia in both transplant groups may only reflect a function of the stressed state of the animals in the immediate postoperative phase.

The effect of ionizing radiation on the primate pancreas: an endocrine and morphologic study.

In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bonemarrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1,000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.

Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate.

The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

Organ allotransplantation since the advent of cyclosporin.

Successful long-term organ transplantation has been made possible by the use of conventional immunosuppression. In contrast with transplantation of other organs, transplantation of the kidney has become an accepted successful form of therapy, 80% of patients being fully rehabilitated. However, complications of therapy are frequent and severe and include bone necrosis, cataract formation, infections and stunted growth in children. The discovery of the immunosuppressive properties of cyclosporin A (CYA) by Borel in 1976 offered new hope to recipients of hepatic, cardiac, pancreatic and heart-lung transplants, since rejection frequently resulted in death. Although the use of CYA has led to significant accomplishments, subsequent studies have documented deleterious side-effects including nephrotoxicity, hepatotoxicity, hirsutism, gingival hyperplasia, tremors and tumours. Yet despite the side-effects, CYA has proved to be a promising immunosuppressive agent for use in human organ transplantation and is at present being evaluated in transplant centres throughout the world.

Recurrent pancreatitis after partial ileal bypass for hyperlipidaemia. A case report.

The case of a 28-year-old man with alcohol-induced bouts of recurrent acute pancreatitis after a partial ileal bypass performed for hyperlipidaemia is presented. Serial computed tomography proved valuable for assessing the resolution of the pancreatic mass. Peripheral parenteral hyperalimentation for 6 weeks had a beneficial effect on the course of the pancreatitis and proved to be useful for nutritional support.

Gangrene of the hand and forearm after inadvertent intra-arterial injection of pyrazole. A case report.

A case of gangrene of the hand following inadvertent intra-arterial injection of a pyrazole derivative (Tomanol) is presented. Gangrene of the hand and superficial sloughing of the distal arm necessitated a forearm amputation. Because of the serious sequelae, precautions must be taken to avoid inadvertent intra-arterial injections and due consideration must be given to the anatomical variation of the brachial artery and its branches in the cubital fossa.

Takayasu's disease. A report of 3 cases.

Three patients with Takayasu's disease are described. In 2 cases aortography demonstrated an occlusion of the great vessels at the origin of the arch of the aorta. In 1 patient there was concomitant aneurysmal dilatation of the brachiocephalic trunk. Common and internal carotid artery stenosis occurred in 1 patient and was associated with hemiplegia and blindness. All 3 patients had constitutional symptoms and signs of the disease as well as markedly elevated erythrocyte sedimentation rates; 2 patients had moderate clinical responses to steroid administration in the short term and 1 developed bilateral calf vein thrombosis, which responded satisfactorily to conservative management.