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Biomedical subjects

G Uhlschmid

Publications and source records attributed to G Uhlschmid.

At least 19 recordsLinked to original sources

Hepatic artery embolisation with a novel radiopaque polymer causes extended liver necrosis in pigs due to occlusion of the concomitant portal vein.

BACKGROUND/AIM: In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc). METHODS: Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation. RESULTS: None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs. CONCLUSIONS: The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.

Animals↗

Tissue engineering: a new approach in cardiovascular surgery: Seeding of human fibroblasts followed by human endothelial cells on resorbable mesh.

OBJECTIVE: In tissue engineering the material properties of synthetic compounds are chosen to enable delivery of dissociated cells onto a scaffold in a manner that will result in in vitro formation of a new functional tissue. The seeding of human fibroblasts followed by human endothelial cells on resorbable mesh is a precondition of a successful creation of human tissues such as vessels or cardiac valves. METHODS: Polymeric scaffolds (n = 18) composed of polyglycolic acid (PGA) with a fiber diameter of 12-15 microm and a polymer density of 70 mg/ml were used as square sheets of 1 x 1 x 0.3 cm. Fibroblasts (passage 7) harvested from human foreskin were seeded (3.4 x 10(6)) and cultured over a 3 week period on a PGA-mesh, followed by seeding of endothelial cells (passage 5, 2.8 x 10(6)) harvested from human ascending aorta. Thereafter the new tissue was stained for HE, van Gieson, Trichrom Masson, Factor VIII and CD 34 and proved by scanning electron microscopy. RESULTS: Microscopic examination of the seeded mesh demonstrated that the human fibroblasts were attached to the polymeric fibers and had begun to spread out and divide. The scanning electron microscopic examination demonstrated a homogeneous scaffold resembling a solid sheet of tissue. The seeded endothelial cells formed a monolayer on the fibroblasts and no endothelial cell invasion or new formation of capillaris could be detected. CONCLUSIONS: These results are a first step to demonstrate that seeding of human fibroblasts and endothelial cells on PGA-mesh might be a feasible model to construct human tissues such as vessels or cardiac valves.

Aorta↗

Tissue engineering: a new approach in cardiovascular surgery--seeding of human fibroblasts on resorbable mesh.

INTRODUCTION: In tissue engineering the material properties of synthetic compounds are manipulated to enable delivery of dissociated cells onto a scaffold in a manner that will result in in vitro formation of new functional tissue. The seeding of human fibroblasts on resorbable mesh is a precondition of a successful creation of human tissue such as autologous cardiac valves. MATERIAL AND METHODS: Polymeric scaffolds (n = 12) composed of polyglycolic acid (PGA) with a fiber diameter of 12-15 mm and a polymer density of 70 mg/ml were used as square sheets of 0.3 x 1 x 1 cm. Fibroblasts (passage 5), harvested from human foreskin, were seeded (3.4 x 10(6)) and cultured over a 3 week period on a PGA mesh. RESULTS: Microscopic examination of the seeded mesh demonstrated that the human fibroblasts were attached to the polymeric fibers and had begun to spread out and to divide. Electron microscopy showed a continuous distribution and formation of the cells throughout the "polymeric architecture". Spotlike hydrolysis of PGA fibers was observed. After 3 weeks the seeded scaffolds resembled a solid sheet of tissue. CONCLUSION: These preliminary results, successful seeding of human fibroblasts on a PGA mesh, represent a first basic step on the way to construct human tissue such as autologous cardiac valves and demonstrate that tissue engineering might be a promising new device in therapy of cardiovascular disease.

Cells, Cultured↗

Experimental cryosurgery of the liver under magnetic resonance guidance.

The feasibility and the advantages of magnetic resonance (MR)-guided interstitial cryosurgery of the liver in an 0.5 Tesla open MR system have been evaluated. Cryosurgery was performed using an Erbocryo PS system with a nonmagnetic cryoprobe of 6 mm diameter. The probe was inserted into the liver parenchyma under real-time MR control. Using continuous MR imaging two freezing cycles of 12 min each were applied. After conventional and dynamic gadolinium-enhanced MR imaging, the animals were sacrificed after 30 min, 3 hr, 24 hr, 7 days, and 21 days. Each lesion was analyzed using light microscopy. A total of seven cryolesions were made in five animals without any complications from cryosurgery. During real-time imaging, cryolesions appeared as a hemispherical growing signal loss with a mean volume of 16.4 cm3. Macroscopic volumes of the lesions showed a good correlation with dynamic enhanced MR images during follow-up, whereas real-time images usually showed an underestimation of the lesion volumes. Cryosurgery of the liver in an open-configuration MR system is a feasible and safe method. MR imaging allows the guidance and the follow-up of cryolesions of the liver with good accuracy.

Animals↗

Magnetic resonance-guided laparoscopic interstitial laser therapy of the liver.

BACKGROUND: There is a necessity for an imaging method during laparoscopy to get a three-dimensional access to the target. In this study we evaluated laparoscopic interstitial laser therapy of the liver under magnetic resonance imaging guidance. METHODS: Five domestic pigs underwent laparoscopy in an open-configuration magnetic resonance system. Under simultaneous real-time magnetic resonance imaging interstitial laser therapy was applied to the liver. Magnetic resonance images, macroscopic aspects of the lesions, and light microscopic findings were compared. RESULTS: The interventions could be safely performed. There was no image artifact caused by instruments or by the carbon dioxide. Dynamic gadolinium-enhanced imaging proved to significantly predict the macroscopic volume of the laser lesions. CONCLUSIONS: Magnetic resonance-guided laparoscopic interstitial laser therapy of the liver combines the advantages of minimal invasive surgery and magnetic resonance imaging. Further development should focus on laparoscopic instruments and temperature sensitive sequences.

Animals↗

MR imaging-guided intravascular procedures: initial demonstration in a pig model.

With use of an open 1.5-T magnetic resonance (MR) imager and a tracking catheter, the authors successfully placed the catheter into the left or right sacral artery in pigs. The tracking catheter comprised a 5.3-F percutaneous transluminal angioplasty catheter with a small copper radio-frequency coil in its tip. With use of the coil as an antenna, the catheter tip position was projected in real time onto MR angiography road maps in two planes. Guidance of placement of the catheter with the MR angiography road maps allowed successful embolization, balloon occlusion, and transjugular intrahepatic puncture of the portal system. Specialized catheters can be tracked in vivo to allow MR guidance in intravascular interventional procedures.

Animals↗

Morphological and functional changes in canine kidneys following extracorporeal shock-wave treatment.

Extracorporeal shock-wave lithotripsy (ESWL) has rapidly become established worldwide as a routine method for treatment of nephro- and ureterolithiasis. Although initial studies showed no tissue-damaging effect by the shock waves, we found, in an animal experiment using canine kidneys, that the ESWL-induced damage to the renal parenchyma is more marked than originally assumed. The damage is limited to the area that was focused on, and heals relatively rapidly by connective tissue encapsulation with final cicatrisation without any further residual effects being observed up to the present. This parenchymal damage is probably also the cause of the macrohematuria that is always observed during therapy. The resulting tissue damage is not extensive enough to cause a demonstrable reduction of function as measured by the usual methods (serum creatinine, creatinine clearance, isotopy renography, i.v. urography). In serum we observed a transient decrease of calcium, an immediate increase of lactate-dehydrogenase, transaminases (SGOT and SGPT) and a delayed increase of alkaline phosphates. Creatinine, blood urea nitrogen, sodium, potassium and amylase remained within normal limits. In urine, a decrease of creatinine and an increase of glucose excretion were noted. We believe that these changes represent a relatively mild and transient damage of renal cells and do not reflect the occasionally heavy morphological changes observed after shock-wave exposure. The main clinical complication is the large subcapsular hematoma which, according to the present knowledge, could well result from a lesion of the larger peripheral vessels. Damage to other organs such as subserous colonic and small bowel hematomata are to be expected although they do not lead to clinical symptoms.

Animals↗

[Experimental aortic aneurysm with endovascular technique].

We created a simple experimental aneurysm by a minimal operative trauma performing the balloon-dilatation and the rupture of the abdominal aorta of animals. The aorta of minipigs was dilated under angiographic control until the rupture became visible. The abdominal aorta and its branches were mapped out and measured. The angiographics were calculated using a planimetric device. The dilatation of the aorta was increased up to 3.5 times the initial diameter when rupture occurred. The microscopical examination showed lesions in all three layers of the vessel only at the rupture site and some focal lesions of the tunica intima. This one-step procedure of producing an experimental aneurysm is done using a low operative trauma and allows testing of endovascular systems using only one anaesthetic.

Aneurysm, Ruptured↗

[The effect of rejection crises and immunosuppressive therapy on the lymphocyte subpopulations of patients after kidney transplantation].

The lymphocyte subsets in the peripheral blood were examined 3 times a week in 17 patients receiving a cadaveric renal allograft using 2-color flow cytometry and several combinations of monoclonal antibodies. Patients who experienced a rejection crisis (n = 12) had a significantly higher CD4/CD8-ratio (2.72 +/- 1.26 mean +/- SD) than patients with stable graft function (1.76 +/- 1.33, p less than 0.05). 9/12 patients showed 0-3 days prior to the rejection episode an increase of the CD4/CD8- ratio (greater than or equal to 0.5) and/or a high ratio (greater than or equal to 2.5) with a decrease following antirejection therapy. The activation markers HLA-DR and IL-2 receptor on T cells were increased only during 3/12 rejection episodes. Patients with rejections resistant to prednisone pulse therapy (n = 6) had significantly more lymphocytes/mm3 in the peripheral blood (1111.7 +/- 597.5) than successfully treated patients (n = 6, 336.7 +/- 196.0, p less than 0.02). Antirejection therapy with prednisone pulses and/or antithymocyte globuline resulted in a significant decrease of T lymphocytes (CD3+) with a selective reduction of T helper/inducer cells (CD4+). 6 months after renal transplantation the patients had a higher percentage of suppressor/cytotoxic cells (CD8+) compared to the pretransplant values (26.3 +/- 10.9% vs 17.7 +/- 6.2%, p less than 0.02) and blood donors (16.3 +/- 6.2%, p less than 0.01). Furthermore the percentage of T helper cells (CD4+/CD28-) was significantly higher and the T suppressor-inducer cells (CD4+/CD28+) were significantly lower compared to the controls. Serial flow cytometric determinations of lymphocyte subsets in renal allograft recipients may be helpful in some cases although rejection episodes could not be predicted in the individual patient.

Adult↗

Post-transplant diabetes mellitus in renal allograft recipients: a matched-pair control study.

The incidence of post-transplant diabetes mellitus was evaluated retrospectively in 901 consecutive renal transplant recipients. Thirty-two (3.6%) patients developed diabetes mellitus requiring drug therapy. 18 of 32 became hyperglycaemic within 3 months of transplantation. Post-transplant diabetes mellitus occurred in 24 of 628 (3.8%) patients treated with conventional therapy consisting in azathioprine and prednisone, and in 8 of 273 (2.9%) patients receiving cyclosporin A (CsA) in addition (triple therapy). To identify predisposing factors 32 non-diabetic patients matched for age, sex, number of graft, immunosuppressive protocol, and graft function at onset of diabetes were used as case controls. Thirteen of 32 patients with diabetes mellitus and 5 of 32 control patients had abnormal glucose tolerance pretransplant (P less than 0.025). HLA-B8 was significantly more frequent in patients with post-transplant diabetes mellitus than in control patients (9 of 29 vs 2 of 31, P less than 0.02). Twelve (38%) patients became diabetic during or immediately after anti-rejection therapy with intravenous pulse prednisone. Four diabetic patients experienced chronic pancreatitis pre-transplant. Family history of diabetes mellitus, bodyweight, number of rejection episodes, and immunosuppressive drug doses were similar in both groups. Actuarial patient and graft survival was not significantly different in diabetic patients and controls, although 10-year data tended to be better in controls. Thus, post-transplant diabetes mellitus was not a frequent complication in patients sometimes predisposed by an impaired glucose tolerance pre-transplant and was triggered by pulse prednisone therapy in 38%.

Adult↗

Injection of microspheres into pancreatic arteries causes acute hemorrhagic pancreatitis in the rat: a new animal model.

Alterations in the vascular bed of the pancreas or disturbances of the blood coagulation system are mostly considered to be sequelae of acute pancreatitis, but it seems that impairment of the pancreatic blood supply can per se lead to acute hemorrhagic pancreatitis. To test this hypothesis with a new animal model, we injected 20 microns polystyrene microspheres retrogradely into the distal splenic artery of rats, thus incompletely blocking blood perfusion in the splenic portion of the pancreas. Eight of eight rats (100%) subjected to microsphere injection developed acute hemorrhagic pancreatitis by 27 h after surgery, when they were killed, but none of the six sham-operated control animals (0%) showed macroscopic signs of pancreatitis. Blood amylase levels at death were 3,087 +/- 650 I.U./L (mean +/- SEM) and the histologic severity score for pancreatitis was 10.8 +/- 1.0 (mean +/- SEM), whereas in the six control rats amylase levels were 1,375 +/- 158 I.U./L and the histology score was only 1.7 +/- 1.0. The result is, with p less than 0.0005, highly significant (chi 2 analysis) and shows that acute experimental pancreatitis can indeed be induced by partially blocking the arterial blood supply within the organ.

Acute Disease↗

[Callus distraction by an internal bone transport system in unilateral fixation].

The problem of the treatment of bone defects can be solved by distraction osteogenesis as developed by ILIZAROV. This study shows how the bone transport technique can be adapted to every common external fixator while using a new internal distraction system. In 20 dogs a bone defect of 6 cm was performed at the femur. The femur was stabilized with an unilateral frame. A proximal or distal corticostomized bone fragment (length 2.5 cm) was descended through the bone defect (1 mm day). In 15 dogs a new regeneration of bone was observed. The quality of the regenerated bone depends upon stability of the fixation. In 5 dogs with osteotomy and rapid dislocation of the transported fragment no bone bridging was found.

Animals↗

[Does extracorporeal shock wave lithotripsy injure the female reproductive tract?].

Female reproductive tract lies near the distal ureter where extracorporeal shock wave lithotripsy (ESWL) of calculi is performed. The question whether ESWL may induce morphological changes in ovary, tube or uterus should be investigated in animal experiments. The female reproductive system of 28 Wistar rats was exposed to 600 or 1200 shock waves. After 24 hours or 35 days the animals were sacrificed and examined by light microscopy and scanning electron microscopy (SEM). Acute after ESWL 2/14 rats revealed minimal subcapsular bleeding in the ovaries. SEM showed a desquamation of superficial cells and a loss in microvilli. In long-term groups there was no morphological lesion. Besides the correlation between healthy and atretic follicles were unchanged. In animal experiment no sign of long lasting changes in female reproductive tract after ESWL could be observed.

Animals↗

[Do shock waves damage the kidney? Morphologic and functional changes of the kidney following exposure to shock waves].

The introduction of extracorporeal shockwave lithotripsy (ESWL) as a routine procedure has brought about a dramatic change in the therapy of urolithiasis. More than 500,000 patients have been treated successfully. Although a tissue damaging effect of the shock wave on the kidney was regarded as non-existent, phenomena such as hematuria during ESWL treatment and subsequent subcapsular hematomas suggest the possibility of damage in the region of the renal parenchyma by the shockwave itself. To investigate this possibility canine kidneys were examined histologically at different intervals after shockwave exposure. Extensive histological changes such as hemorrhage and sometimes direct tubular damage were found, with scar formation after three months. These changes are limited to the areas exposed to ESWL treatment.

Animals↗

Cyclosporine A impairs wound healing of ureterocystoneostomy in rats. Scanning electron microscopic examination.

The effect of cyclosporine A (CsA), an immunosuppressive agent used in transplantation, on wound healing following microsurgical neoimplantation of a ureter in the bladder of 63 SIV ZUR rats was examined morphologically using the light and scanning electron microscopes and functionally by radiography. Following ureterocystoneostomy (UCN) on the right side, the animals in Group I (control group) received 1.0 ml CsA solvent (0.1 g ethanol and 0.3 g intralipid) per day. Group II received 12.5 mg/kg/day CsA and Group III 17.5 mg/kg/day CsA. All drugs were administered i.p. A third of the animals in each group were reoperated 7, 14 or 28 days after UCN. At these time intervals, there were no radiologically demonstrable differences in the operated side. Examination under the scanning electron microscope indicated delayed restitution of epithelium in the bladder for rats which had received CsA as compared to the control group. In the area of the UCN, CsA caused dose-independent retardation of the regenerative hyperplasia associated with wound healing (Group I: max. 7 days after UCN: Group II and Group III, max. 14 days after UCN). Hyperplastic areas had ropy microridges and uniform short microvilli. Where the hyperplasia exhibited nodular and papillary formation, also histologically more evident under CsA, occasional epithelial cells had pleomorphic microvilli on their luminal surface. Unlike other known premalignant changes of this kind, the frequent occurrence of pleomorphic microvilli under CsA was reversible. In general, CsA led to dose-unrelated protraction of UCN wound healing with no lasting functional disturbance in rats.

Animals↗

[Experimental pancreatic duct occlusion with polyurethane].

Pancreatic transplantation requires an effective method to manage exocrine secretion. A new technique to eliminate the exocrine function of the pancreas by obstruction of the duct with polyurethane was investigated in terms of function, outcome and morphology. Polyurethane is an alcoholic solution of block copolymers with the property of polymerizing within 5-10 min. In this study the in-situ pancreatic tail model in dogs was utilized, the pancreatic duct was cannulated and injected with 2-3 ml of polyurethane. As a result, complete atrophy and fibrosclerosis of the exocrine tissue was obtained leaving islets well vascularized and functioning for the entire experimental periods. All animals remained normoglycemic and showed normal K-values. Amylase levels were found to be maximally elevated at 24 h and returned to normal within 2 weeks after duct occlusion. Insulin, glucagon and somatostatin levels remained normal. Because of its ability to effect a complete occlusion of the pancreatic ducts with subsequent atrophy of the exocrine gland and without notable disturbance of endocrine function, we feel that polyurethane solution is superior to previously used materials for this purpose.

Animals↗

Morphological changes in canine kidneys following extra-corporeal shock wave treatment.

Extracorporal shock wave lithotripsy has rapidly become established world wide as a routine method for treatment of nephro- and ureterolithiasis. Although initial studies showed no tissue damaging effect by the shock waves, we found in an animal experiment using canine kidneys, the ESWL induced damage to the renal parenchyma is more marked than originally assumed. The damage is limited to the area that was focused on, and heals relatively rapidly by connective tissue encapsulation with final cicatrisation without any further residual effects being observed until now. This parenchymal damage is probably also the cause of the macrohaematuria that is always observed during therapy. The resulting tissue damage is not extensive enough to cause demonstrable reduction of function as measured by the usual methods (serum creatinine, creatinine clearance, isotopy renography, i/v-urography). The main clinical complication is the large subcapsular haematoma which, according to present knowledge, could well result from a lesion of the larger peripheral vessels. Damage to other organs such as subserous colonic and small bowel haematomata are to be expected although they do not lead to clinical symptoms.

Animals↗