Biomedical subjects

W M Fritschy

Publications and source records attributed to W M Fritschy.

10 recordsLinked to original sources

PubMed2005

Autogenous radial-cephalic or prosthetic brachial-antecubital forearm loop AVF in patients with compromised vessels? A randomized, multicenter study of the patency of primary hemodialysis access.

OBJECTIVE: The construction of an autogenous radial-cephalic direct wrist arteriovenous fistula (RCAVF) is the primary and best option for vascular access for hemodialysis. However, 10%-24% of RCAVFs thrombose directly after operation or do not function adequately due to failure of maturation. In case of poor arterial and/or poor venous vessels for anastomosis, the outcome of RCAVFs may be worse and an alternative vascular access is probably indicated. A prosthetic graft implant may be a second best option. Therefore, a randomized multicenter study comparing RCAVF with prosthetic (polytetrafluoroethylene [PTFE]) graft implantation in patients with poor vessels was performed. METHODS: A total of 383 consecutive new patients needing primary vascular access were screened for enrollment in a prospective randomized study. According to defined vessel criteria from the preoperative duplex scanning, 140 patients were allocated to primary placement of an RCAVF and 61 patients to primary prosthetic graft implantation. The remaining 182 patients were randomized to receive either an RCAVF (n = 92) or prosthetic graft implant (n = 90). Patency rate was defined as the percentage of AVFs that functioned well after implantation. RESULTS: Primary and assisted primary 1-year patencies were 33% +/- 5.3% vs 44% +/- 6.2% (P = .03) and 48% +/- 5.5% vs 63% +/- 5.9% (P = .035) for the RCAVF and prosthetic AVF, respectively. Secondary patencies were 52% +/- 5.5% vs 79% +/- 5.1% (P = .0001) for the RCAVF and prosthetic AVF, respectively. Patients with RCAVFs developed a total of 102 (1.19/patient-year [py]) vs 122 (1.45/py; P = .739) complications in the prosthetic AVFs. A total of 43 (0.50/py) interventions in the RCAVF group and 79 (0.94/py) in the prosthetic graft group were needed for access salvage (P = .077). CONCLUSIONS: Although there were more interventions needed for access salvage in the patients with prosthetic graft implants, we may conclude that patients with poor forearm vessels do benefit from implantation of a prosthetic graft for vascular access.

Aged↗

PubMed1995

Glycol methacrylate embedding of alginate-polylysine microencapsulated pancreatic islets.

A method for processing and embedding alginate-polylysine microencapsulated pancreatic tissue in glycol methacrylate resin (GMA) is described. Fixation in 4% phosphate buffered formaldehyde, processing in ascending concentrations of glycol methacrylate monomer and embedding in Technovit 7100 results in well preserved morphological details of hydrogels, hydrogel-cell interfaces, and encapsulated pancreatic tissue. Routine staining with Loeffler's methylene blue, hematoxylin and eosin, and Romanovsky-Giemsa gave excellent images of the GMA embedded alginate polylysine membrane and tissues allowing cells on the outside of the capsule to be analyzed effectively as part of the foreign body reaction against the capsule membrane.

Alginates↗

PubMed1994

The capsular overgrowth on microencapsulated pancreatic islet grafts in streptozotocin and autoimmune diabetic rats.

This study investigates whether capsular overgrowth on alginate-polylysine microencapsulated islets is influenced by (1) the presence of islet tissue, (2) MHC incompatibility between donor and recipient, or (3) the presence of autoimmune diabetes. Encapsulated Albino Oxford (AO, n = 6, isografts) and Lewis (n = 6, allografts) rat islets, and encapsulated human islets (n = 5, xenografts) were implanted intraperitoneally into streptozotocin-diabetic AO rats. Also, encapsulated AO islets were implanted into autoimmune diabetic Bio Breeding/Organon (BB/O) rats (n = 5, allografts). Five isografts, five allografts, and three xenografts in AO recipients and five allografts in BB/O recipients resulted in normoglycemia. Two weeks after implantation, islets containing capsules were retrieved by peritoneal lavage, after which all animals that had become normoglycemic after transplantation returned to a state of hyperglycemia. Recovery rates of the capsules of these successful grafts, expressed as percentages of the initially implanted graft volume, varied from 72% +/- 7% to 80% +/- 9%. The associated pericapsular infiltrates (PCI) were similar in all groups and varied from 3.2% +/- 1.4% to 8.3% +/- 2.6%. Similar recovery rates and PCI were also found with empty capsules. However, the recovery rates of recipients with graft failures were lower and showed more PCI. Immunohistological staining of PCI showed no differences in the types of cells in the PCI on capsules with or without islets. We conclude that this early PCI is a capsule-induced foreign body reaction that is not influenced by MHC incompatibility or by the presence of autoimmune diabetes, and it should be avoided by improving the biocompatibility of the capsules.

Alginates↗

PubMed1993

Obstacles in the application of microencapsulation in islet transplantation.

Several factors stand in the way of successful clinical transplantation of alginate-polylysine-alginate microencapsulated pancreatic islets. These obstacles can be classified into three categories. The first regards the technical aspects of the production process. Limiting factors are the insufficient ability to produce small capsules with an adequate production rate, and insufficient insight into the factors determining the optimal chemical and mechanical properties of the capsules. The second category regards the functional aspects of the microencapsulated islets, such as the limitations of the transplantation site and the absence of a physiologic insulin response of the encapsulated islets to elevated blood glucose levels. The third category regards the fact that survival times of encapsulated islet grafts are still limited to several weeks or months, which is mainly explained by a pericapsular fibrotic overgrowth reaction as a consequence of the bioincompatibility of the capsule membrane. This study describes these obstacles, and thereby summarizes the requirements needed for successful clinical application of encapsulated islet transplantation.

Alginates↗

PubMed1992

Comparison of top and bottom loading of a dextran gradient for rat pancreatic islet purification.

Rat pancreatic islet yields obtained with dextran gradient purification were compared after suspending the digest into either the top or the bottom layer of the gradient. A 5-layer discontinuous gradient was used, which consisted of 16 ml 31% dextran as bottom layer, overlayered with 25%, 23%, 20% and 11% dextran (4 ml each). When the digest of 1 rat pancreas was suspended into the top layer of the gradient, the total number of islets obtained from the 11-20, 20-23 and 23-25% interfaces was 862 +/- 38, 240 +/- 39 and 54 +/- 5, respectively. From this gradient, also 1409 +/- 81 islets were retrieved from the bottom layer (i.e., exocrine pellet). In contrast, when the pancreas digest was suspended into the bottom layer of the gradient, 1964 +/- 63, 435 +/- 42, and 177 +/- 34 islets were obtained from the successive interfaces, and only 50 +/- 20 islets from the exocrine pellet. The total islet volume obtained from the two uppermost interfaces was 3.46 +/- 0.31 microliters after top-loading, and 4.93 +/- 0.16 microliters after bottom-loading (n = 7, p < 0.01). When the islets retrieved from one bottom loaded gradient were transplanted into either 1 (n = 6) or 2 (n = 9) diabetic recipients, glucose levels normalized in all instances. We therefore conclude that a bottom-loaded dextran gradient separates islets from exocrine tissue effectively, resulting in significantly higher islet yields than obtained with a top-loaded dextran gradient.

Animals↗

PubMed1991

A versatile alginate droplet generator applicable for microencapsulation of pancreatic islets.

Alginate beads for immunoisolation of pancreatic islets by microencapsulation should be small, smooth, and spherical in order to ensure that around the islets a strong alginate-polylysine-alginate capsule will be formed with optimal biocompatibility and diffusion of nutrients and hormones. However, the preparation of small capsules around islets is difficult. Our newly designed air jet droplet generator allows for variations in the length and diameter of the alginate nozzle and the air jacket and is in this way adaptable to a required bead size. Alginate droplets are converted into rigid beads in a 100 mM CaCl 2 solution. Their size depends upon the diameter of the jacket, the air flow rate, and the outer diameter of the nozzle, whereas the production rate depends upon the pressure on the alginate, and on the diameter and the length of the nozzle. When the air flow or the alginate flow surpasses a certain rate, the droplets are fragmented. This study describes the mutual relationship of these variables and defines their optimal range for reproducible production of smooth and spherical beads for microencapsulation of islets at an acceptable production rate.

Alginates↗

PubMed1991

Glucose tolerance and plasma insulin response to intravenous glucose infusion and test meal in rats with microencapsulated islet allografts.

Albino Oxford rats made diabetic with 75 mg/kg streptozotocin were intraperitoneally transplanted with 2500-2900 alginate-polylysine microencapsulated Lewis islets (n = 9, total islet tissue volume 8.0-11.0 microliters), or a similar volume of non-encapsulated Lewis islets (n = 5). All rats with microencapsulated islets became normoglycaemic, and remained normoglycaemic for 5-16 weeks. In rats with non-encapsulated islet grafts, only a temporary decrease in blood glucose was observed, and all were again severely hyperglycaemic at 1 week after implantation. At 5-6 weeks after transplantation, glucose tolerance in rats with microencapsulated islets was tested by intravenous glucose infusion (10 mg/min over 20 min) and test meal administration (n = 4). During glucose infusion, maximum glucose levels were 13.0 +/- 0.4 mmol/l in rats with microcapsules and 8.9 +/- 0.4 mmol/l in healthy control rats (p less than 0.01). Concomitant maximum plasma insulin levels were 215 +/- 17 pmol/l in rats with microcapsules and 715 +/- 85 pmol/l in controls (p less than 0.001). After the test meal, maximum blood glucose was 10.6 +/- 0.9 mmol/l in rats with microcapsules and 6.2 +/- 0.1 mmol/l in controls (p less than 0.001), with concomitant maximum plasma insulin levels of 247 +/- 11 pmol/l and 586 +/- 59 pmol/l, respectively (p less than 0.001). In conclusion, although the glucose tolerance is impaired and plasma insulin responses to intravenous glucose-load and test-meal are reduced, the alginate-polylysine membrane does provide adequate immunoisolation for the prolongation of allograft survival, resulting in prolonged normoglycaemia in streptozotocin diabetic rats.

Animals↗

PubMed1991

The efficacy of intraperitoneal pancreatic islet isografts in the reversal of diabetes in rats.

The peritoneal cavity is of renewed interest for pancreatic islet transplantation, since it is the preferable site for transplantation of immunoisolated islets. In this study we investigated the minimum islet graft volume needed to restore normoglycemia after free intraperitoneal isogenic transplantation in streptozotocin diabetic rats. Furthermore, graft function was tested by measuring glucose and insulin response to an intravenous glucose load and spontaneously ingested carbohydrate-rich meal. Three graft volumes were used: 8.0-10.0 (group A); 4.0-5.0 (group B); and 2.0-2.3 microliters (group C); 1 microliter contained about 300 islets. All 10 rats in group A and 7 out of 9 rats in group B became normoglycemic for at least 6 months posttransplant, with blood glucose levels not significantly different from normal control animals. Only 3 out of 9 animals in group C became normoglycemic and never for longer than 3 months. The insulin responses to IVGTT in group A and group B were proportional to the grafted islet volume and always significantly lower than those of normal control rats. The insulin response to the test meal showed a similar tendency, which was found to be associated with the absence of preabsorptive insulin secretion. Maximum postprandial blood glucose levels in group A and group B were 0.8 and 1.5 mM higher than in normal control rats. We conclude that intraperitoneal transplantation of at least 4.0-5.0-microliters islet tissue is needed to reverse blood glucose in streptozotocin diabetic rats, and that glucose and insulin levels on IVGTT and test meal in rats with islet grafts of 8.0-10.0 microliters are not completely normalized. It is suggested that the impaired glucose tolerance is due to an insufficient beta-cell mass and a lack of parasympathetic innervation of the transplanted islet tissue.

Animals↗

PubMed1991

Effect of alginate-polylysine-alginate microencapsulation on in vitro insulin release from rat pancreatic islets.

We investigated the effect of alginate-polylysine-alginate microencapsulation on glucose-induced insulin secretion by rat islets. Applying the encapsulation method originally described by Lim, we found severely reduced in vitro insulin release (expressed as picomoles of insulin.10 islets-1.45 min-1 when incubated in 16.5 mM glucose), because the insulin release with encapsulated islets was 1.42 +/- 0.49 compared to 13.58 +/- 0.80 with free control islets. This could not be explained by inadequate permeability of the capsule, because insulin release was also severely reduced (2.12 +/- 0.61) when islets were subjected to the procedure but without the membrane-forming polylysine step. Therefore, islets were tested after having been subjected separately to each of the steps of the procedure. Insulin release was not affected by either alginate or CaCl2 but was severely reduced after prolonged suspension in saline or treatment with citrate. When saline and citrate were replaced by Ca2(+)-free Krebs-Ringer bicarbonate buffer (KRBB) and 1 mM EGTA, respectively, insulin release improved significantly both with complete and with incomplete (no polylysine step) encapsulation. This outcome was verified in a set of experiments run in parallel with islets derived from the same isolation procedure. Insulin release was 1.20 +/- 0.23 from islets encapsulated with the method of Lim and 10.73 +/- 1.04 from free control islets. With the modified procedure, insulin release was 9.17 +/- 0.52 vs. 9.61 +/- 1.27 for complete versus incomplete encapsulation, respectively. We conclude that Ca2(+)-free KRBB instead of saline and EGTA instead of citrate should be used to obtain an adequate insulin response from encapsulated islets and that the capsule membrane as such has no influence on glucose and insulin diffusion.

Alginates↗

PubMedDate not supplied

Primary cardiac tumors.

From 1970 to 1986, 3 males and 6 females, ranging in age from 13 to 69 years (median 45 years), underwent heart surgery for a primary cardiac tumor. Six patients had a left atrial myxoma; a lipofibroma, a lymphosarcoma and a rhabdomyosarcoma were found each in 1 patient. The following complaints were present: congestive heart failure in 8, fatigue in 7, cardiac arrhythmia in 3, palpitations in 3, fever in 2 and finally weight loss, nocturnal perspiration and clubbing were each in one patient. The duration of symptoms ranged from 6 weeks to more than 2 years (median 10.8 months). All patients were operated with the aid of extracorporeal circulation as soon as they were diagnosed. One patient with extensive tumor growth died at the end of the procedure. During the follow-up period all patients with a primary malignant tumor died within 3 months. Those with myxoma or fibroma are still alive with a follow-up period extending to 13 years (median 7 years). All surviving patients are asymptomatic and well. Malignant cardiac tumors do have a very poor prognosis, they are only amenable for palliative resection and even then prognosis remains poor. When an endocardial biopsy confirms the diagnosis of a cardiac malignancy, the indication for operation is questionable, although there is an absolute indication in case of obstruction. Cardiac myxoma should be resected after diagnosis because the potential embolic complications may be debilitating or lethal. The operative risk is small, and the long term results are excellent.

Adolescent↗